Virus 59929 225761621 2008-07-15T07:57:04Z Katimawan2005 3530824 Link to Kapampangan {{Otheruses4|the biological agent|computer viruses|Computer virus}} {{otheruses}} {{Taxobox | color = violet | name = Viruses | image = Rotavirus Reconstruction.jpg | image_caption = Rotavirus | virus_group = I–VII | subdivision_ranks = Groups | subdivision = I: [[dsDNA virus]]es<br /> II: [[ssDNA virus]]es<br /> III: [[dsRNA virus]]es<br /> IV: [[positive-sense ssRNA virus|(+)ssRNA virus]]es<br /> V: [[negative-sense ssRNA virus|(-)ssRNA virus]]es<br /> VI: [[ssRNA-RT virus]]es<br /> VII: [[dsDNA-RT virus]]es }} {{seeintro}} A '''virus''' (from the [[Latin]] ''virus'' meaning "[[toxin]]" or "[[poison]]"), is a [[Optical microscope#Limitations of light microscopes|sub-microscopic]] infectious agent that is unable to grow or reproduce outside a [[host (biology)|host]] [[cell (biology)|cell]]. Each viral particle, or ''virion'', consists of genetic material, [[DNA]] or [[RNA]], within a protective protein coat called a [[capsid]]. The capsid shape varies from simple helical and icosahedral (polyhedral or near-spherical) forms, to more complex structures with tails or an [[viral envelope|envelope]]. Viruses infect all cellular life forms and are grouped into animal, plant and bacterial types, according to the type of host infected. Examples of common human diseases caused by viruses include the [[common cold]], [[influenza]], [[chickenpox]], [[Rotavirus|diarrhea]] and [[cold sores]]. Serious diseases such as [[Ebola]], [[AIDS]], [[avian influenza]] and [[SARS]] are caused by viruses. The relative ability of viruses to cause disease is described in terms of [[virulence]]. Viruses have different mechanisms by which they produce disease in an organism, which largely depends on the species. Mechanisms at the cellular level primarily include cell [[lysis]], the breaking open and subsequent death of the cell. In [[multicellular organism]]s, if enough cells die the whole organism will start to suffer the effects. Although viruses cause disruption of healthy [[homeostasis]], resulting in disease, they may exist relatively harmlessly within an organism. An example would include the ability of the [[herpes simplex virus]], which cause cold sores, to remain in a dormant state within the human body. This is called latency, and is a characteristic of the [[herpes viruses]] including the [[Epstein-Barr virus]], which causes glandular fever, and the [[Varicella zoster]] virus, which causes chicken pox. Latent chickenpox infections return in later life as the disease called [[shingles]]. Some viruses can cause life-long or [[Chronic (medical)|chronic]] infections, where the viruses continue to replicate in the body despite the hosts' defense mechanisms. [[Biology|Biologists]] debate whether or not viruses are living [[organisms]]. Some consider them non-living as they do not meet all the criteria used in the common definitions of [[life]]. For example, unlike most organisms, viruses do not have [[Cell (biology)|cells]]. However, viruses have genes and evolve by [[natural selection]]. Others have described them as organisms at the edge of life. Viral infections in human and animal hosts usually result in an immune response and [[disease]]. Often, a virus is completely eliminated by the [[immune system]]. [[Antibiotic]]s have no effect on viruses, but [[antiviral drug]]s have been developed to treat life-threatening infections. [[Vaccine]]s that produce lifelong [[immunity (medical)|immunity]] can prevent viral infections. == Etymology == The word is from the [[Latin]] ''virus'' referring to [[poison]] and other noxious substances, first used in English in 1392.<ref name=Etymology_Dictionary>{{cite web |title = virus |work = The Online Etymology Dictionary |url = http://www.etymonline.com/index.php?term=virus |accessdate = 2007-07-16 }}</ref> ''Virulent'', from Latin ''virulentus'', "poisonous", dates to 1400.<ref name=OED>{{cite web |title = virulent, a. |work = The Oxford English Dictionary - Online |url = http://dictionary.oed.com |accessdate = 2007-07-16 }}</ref> A meaning of "agent that causes infectious disease" is first recorded in 1728,<ref name=Etymology_Dictionary/> before the discovery of viruses by the [[Russians|Russian]]-[[Ukrainians|Ukrainian]] [[biologist]] [[Dmitry Ivanovsky]] in 1892. The adjective ''viral'' dates to 1948.<ref name=OED2>{{cite web |title = viral, a. |work = The Oxford English Dictionary - Online |url = http://dictionary.oed.com |accessdate = 2007-07-16 }}</ref> Today, ''virus'' is used to describe the biological viruses discussed above and as a [[metaphor]] for other parasitically-reproducing things, such as [[meme]]s or [[computer virus]]es (since 1972).<ref name=OED/> The term ''virion'' is also used to refer to a single infective viral particle. The English plural form of ''virus'' is ''viruses''; see [[Plural of virus]]. ==Discovery of viruses== Viral diseases such as [[rabies]], [[yellow fever]] and [[smallpox]] have affected humans for centuries. There is hieroglyphical evidence of [[polio]] in [[ancient Egyptian medicine]],<ref>Paul GF. (1971) A History of Poliomyelitis. Yale University Press: New Haven and London.</ref> though the cause of this disease was unknown at the time. In the 10th century, [[Muhammad ibn Zakarīya Rāzi]] (Rhazes) wrote the ''Treatise on Smallpox and Measles'', in which he gave the first clear descriptions of smallpox and [[measles]].<ref>Abdul Nasser Kaadan (2007), [http://muslimheritage.com/topics/default.cfm?ArticleID=682 Al-Razi on Smallpox and Measles], FSTC</ref> In 1717, [[Lady Mary Wortley Montagu|Mary Montagu]], the wife of an English ambassador to the [[Ottoman Empire]], observed local women [[inoculation|inoculating]] their children against [[smallpox]].<ref name=Behbehani_1983>{{cite journal |author=Behbehani AM |title=The smallpox story: life and death of an old disease |journal=Microbiol Rev |volume=47 |issue=4 |pages=455–509 |year=1983 |pmid=6319980 |doi=10.1002/rmv.443 }}</ref> In the late 18th century, [[Edward Jenner]] observed and studied Miss Sarah Nelmes, a milkmaid who had previously caught [[cowpox]] and was found to be immune to [[smallpox]], a similar, but devastating virus. Jenner developed the smallpox [[vaccine]] based on these findings. After lengthy [[vaccination]] campaigns, the [[World Health Organization]] (WHO) certified the eradication of [[smallpox]] in 1979. In the late 19th century, [[Charles Chamberland]] developed a porcelain filter with pores small enough to remove cultured bacteria from their culture medium.<ref name=Horzinek_1997>{{cite journal |author = Horzinek MC |title = The birth of virology |journal = Antonie van Leeuwenhoek |year = 1997 |volume = 71 |pages = 15&ndash;20 |doi=10.1023/A:1000197505492 }}</ref> [[Dimitri Ivanovski]] used this filter to study an infection of tobacco plants, now known as [[tobacco mosaic virus]]. He passed crushed leaf extracts of infected tobacco plants through the filter, then used the filtered extracts to infect other plants, thereby proving that the infectious agent was not a bacterium. Similar experiments were performed by several other researchers, with similar results. These experiments showed that viruses are [[orders of magnitude]] smaller than bacteria. The term ''virus'' was coined by the Dutch microbiologist [[Martinus Beijerinck]], who showed, using methods based on the work of Ivanovski, that tobacco mosaic disease is caused by something smaller than a bacterium. He coined the Latin phrase "contagium vivum fluidum" (which means "soluble living germ") as the first idea of the virus. <ref>[http://www.asm.org/ASM/files/CCLIBRARYFILES/FILENAME/0000000251/621096p539.pdf|Chung, King-Thom and Ferris, Deam Hunter (1996). Martinus Willem Beijerinck (1851-1931): pioneer of general microbiology. AMS News 62,539-543]</ref> In the early 20th century, [[Frederick Twort]] discovered that bacteria could be infected by viruses.<ref> [http://encyclopedia.jrank.org/Cambridge/entries/067/Frederick-William-Twort.html|Frederick William Twort]</ref> [[Felix d'Herelle]], working independently, showed that a preparation of viruses caused areas of cellular death on thin [[cell culture]]s spread on [[agar]]. Counting the dead areas allowed him to estimate the original number of viruses in the suspension. The invention of [[electron microscopy]] provided the first look at viruses. In 1935, [[Wendell Stanley]] crystallized the tobacco mosaic virus and found it to be mostly [[protein]].<ref name="pmid17756690">{{cite journal |author=Stanley WM, Loring HS |title=The Isolation of Crystalline Tobacco Mosaic Virus Protein from Diseased Tomato Plants |journal=Science |volume=83 |issue=2143 |pages=85 |year=1936 |pmid=17756690 |doi=10.1126/science.83.2143.85 }}</ref> A short time later, the virus was separated into protein and [[nucleic acid]] parts.<ref name="pmid17788438">{{cite journal |author=Stanley WM, Lauffer MA |title=Disintegration of Tobacco Mosaic Virus in Urea Solutions |journal=Science |volume=89 |issue=2311 |pages=345–347 |year=1939 |pmid=17788438 |doi=10.1126/science.89.2311.345 }}</ref><ref name="pmid16590772">{{cite journal |author=Tsugita A, Gish DT, Young J, Fraenkel-Conrat H, Knight CA, Stanley WM |title=The Complete Aino Acid Sequence of the Protein of Tobacco Mosaic Virus |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=46 |issue=11 |pages=1463–9 |year=1960 |pmid=16590772 | doi = 10.1073/pnas.46.11.1463 }}</ref> In 1939, [[Max Delbrück]] and E.L. Ellis demonstrated that, in contrast to cellular organisms, bacteriophage reproduce in "one step", rather than exponentially.<ref name="pmid16791793">{{cite journal |author=Pennazio S |title=The origin of phage virology |journal=Riv. Biol. |volume=99 |issue=1 |pages=103–29 |year=2006 |pmid=16791793 }}</ref> A major problem for early virologists was the inability to propagate viruses on sterile culture media, as is done with cellular microorganisms. This limitation required medical virologists to infect living animals with infectious material, which is dangerous. The first breakthrough came in 1931, when [[Ernest William Goodpasture]] demonstrated the growth of [[influenza]] and several other viruses in fertile chicken eggs.<ref name="pmid17810781">{{cite journal |author=Goodpasture EW, Woodruff AM, Buddingh GJ |title=The Cultivation of Vaccine and Other Viruses in the Chorioallantoic Membrane of Chick Embryos |journal= Science |volume=74 |issue=1919 |pages=371–372 |year=1931 |pmid=17810781 |doi=10.1126/science.74.1919.371 }}</ref> However, some viruses would not grow in chicken eggs, and a more flexible technique was needed for propagation of viruses. The solution came in 1949 when [[John Franklin Enders]], [[Thomas H. Weller]] and [[Frederick Chapman Robbins]] together developed a technique to grow the [[polio virus]] in cultures of living animal cells.<ref name="pmid15470207">{{cite journal |author=Rosen FS |title=Isolation of poliovirus--John Enders and the Nobel Prize |journal=N. Engl. J. Med. |volume=351 |issue=15 |pages=1481–3 |year=2004 |pmid=15470207 |doi=10.1056/NEJMp048202 }}</ref> Their methods have since been extended and applied to the growth of viruses and other infectious agents that do not grow on sterile culture media. ==Origins== The origin of modern viruses is not entirely clear. It may be that no single mechanism can account for their origin.<ref>Holmes EC, Drummond AJ. The evolutionary genetics of viral emergence.Curr Top Microbiol Immunol. 2007;315:51-66.</ref> They do not [[fossil]]ize well, so [[Molecular biology|molecular techniques]] have been the most useful means of hypothesising how they arose.<ref>Liu Y, Nickle DC, Shriner D, Jensen MA, Learn GH Jr, Mittler JE, Mullins JI. Molecular clock-like evolution of human immunodeficiency virus type 1.Virology. 2004 Nov 10;329(1):101-8.</ref> Research in [[microfossil]] identification and molecular biology may yet discern fossil evidence dating to the [[Archean]] or [[Proterozoic]] [[eon (geology)|eons]]. Two main hypotheses currently exist.<ref name="prescott">{{cite book |title=Microbiology |last=Prescott |first=L |date=1993 |publisher=Wm. C. Brown Publishers |id=0-697-01372-3 }}</ref> Small viruses with only a few genes may be runaway stretches of nucleic acid originating from the genome of a living organism. Their genetic material could have been derived from transferable genetic elements such as [[plasmid]]s or [[transposon]]s, that move within, leave, and enter genomes. New viruses are emerging ''[[de novo]]'' and therefore, it is not always the case that viruses have ancestors.<ref>Keese P, Gibbs A. Plant viruses: master explorers of evolutionary space.Curr Opin Genet Dev. 1993 Dec;3(6):873-7.</ref> Viruses with larger genomes, such as [[poxvirus]]es, may have once been small cells that parasitized larger host cells. Over time, genes not required by their parasitic lifestyle would have been lost in a streamlining process known as ''retrograde-evolution'' or ''reverse-evolution''. The bacteria ''[[Rickettsia]]'' and ''[[Chlamydia (bacterium)|Chlamydia]]'' are living cells that, like viruses, can only reproduce inside host cells. They lend credence to the streamlining hypothesis, as their parasitic lifestyle is likely to have led to the loss of genes that enabled them to survive outside a host cell. It is possible that viruses represent a primitive form of self replicating DNA and are a precursor to life as it is currently defined.<ref>Koonin EV. The Biological Big Bang model for the major transitions in evolution.Biol Direct. 2007 Aug 20;2:21.</ref> Other infectious particles which are even simpler in structure than viruses include [[viroid]]s, [[satellite (biology)|satellites]], and [[prion]]s. ==Classification== {{main|Virus classification}} In [[taxonomy]], the classification of viruses is difficult owing to the lack of a fossil record and the dispute over whether they are living or non-living.<ref> Rybicki EP (1990) The classification of organisms at the edge of life, or problems with virus systematics. S Aft J Sci 86:182-186</ref><ref name="pmid13481308">{{cite journal |author=LWOFF A |title=The concept of virus |journal=J. Gen. Microbiol. |volume=17 |issue=2 |pages=239–53 |year=1957 |pmid=13481308 |doi=}}</ref> They do not fit easily into any of the [[domain (biology)|domains]] of [[biological classification]], and classification begins at the [[family (biology)|family]] rank. However, the domain name of [[Acytota]] (without cells) has been suggested. This would place viruses on a par with the other domains of [[Eubacteria]], [[Archaea]], and [[Eukarya]]. Not all families are currently classified into orders, nor all genera classified into families. In 1962, [[André Lwoff]], [[Robert Horne]], and [[Paul Tournier]] were the first to develop a means of virus classification, based on the [[Linnaean taxonomy|Linnaean]] hierarchical system.<ref name="pmid14467544">{{cite journal |author=Lwoff A, Horne RW, Tournier P |title=A virus system |language=French |journal=C. R. Hebd. Seances Acad. Sci. |volume=254 |issue= |pages=4225–7 |year=1962 |pmid=14467544 |doi=}}</ref> This system based classification on [[phylum]], [[class (biology)|class]], [[order (biology)|order]], [[family (biology)|family]], [[genus]], and [[species]]. Viruses were grouped according to their shared properties (not of their hosts) and the type of nucleic acid forming their genomes.<ref name="pmid13931895">{{cite journal |author=Lwoff A, Horne R, Tournier P |title=A system of viruses |journal=Cold Spring Harb. Symp. Quant. Biol. |volume=27 |issue= |pages=51–5 |year=1962 |pmid=13931895 |doi=}}</ref> Following this initial system, a few modifications were made and the [[International Committee on Taxonomy of Viruses]] was developed (ICTV). ====ICTV classification==== The [[International Committee on Taxonomy of Viruses]] (ICTV) developed the current classification system and put in place guidelines that put a greater weighting on certain virus properties to maintain family uniformity. A universal system for classifying viruses, and a unified taxonomy, has been established since 1966. In determining order, taxonomists should consider the type of nucleic acid present, whether the nucleic acid is single- or double-stranded, and the presence or absence of an [[Envelope (biology)|envelope]]. After these three main properties, other characteristics can be considered: the type of host, the capsid shape, immunological properties and the type of disease it causes. The system makes use of a series of ranked [[taxon]]s. The general structure is as follows: :[[Order (biology)|Order]] (''-virales'') ::[[Family (biology)|Family]] (''-viridae'') :::[[Subfamily]] (''-virinae'') ::::[[Genus]] (''-virus'') :::::[[Species]] (''-virus'') The recognition of orders is very recent; to date, only three have been named, and most families remain unplaced. The committee does not formally distinguish between subspecies, strains, and isolates. In total there are three orders, 56 families, nine subfamilies, and 233 genera. ICTV recognizes about 1,550 virus species, but about 30,000 virus strains and isolates are being tracked by virologists.<ref> Virus Taxonomy 8th Reports of the International Committee on Taxonomy of Viruses C.M. Fauquet, M.A. Mayo, J. Maniloff, U. Desselberger, and L.A. Ball (eds) Academic Press, 1162 pp. (2005) Elsevier Publication Date: 27 May 2005 </ref> The [[Nobel Prize]]-winning biologist [[David Baltimore]] devised the [[Virus classification#Baltimore classification|Baltimore classification]] system.<ref name="pmid4377923">{{cite journal |author=Baltimore D |title=The strategy of RNA viruses |journal=Harvey Lect. |volume=70 Series |issue= |pages=57–74 |year=1974 |pmid=4377923 |doi=}}</ref><ref name="pmid4348509">{{cite journal |author=Temin HM, Baltimore D |title=RNA-directed DNA synthesis and RNA tumor viruses |journal=Adv. Virus Res. |volume=17 |issue= |pages=129–86 |year=1972 |pmid=4348509 |doi=}}</ref> The ICTV classification system is used in conjunction with the Baltimore classification system in modern virus classification.<ref name="pmid15078590">{{cite journal |author=van Regenmortel MH, Mahy BW |title=Emerging issues in virus taxonomy |journal=Emerging Infect. Dis. |volume=10 |issue=1 |pages=8–13 |year=2004 |pmid=15078590 |doi=}}</ref><ref name="pmid10486120">{{cite journal |author=Mayo MA |title=Developments in plant virus taxonomy since the publication of the 6th ICTV Report. International Committee on Taxonomy of Viruses |journal=Arch. Virol. |volume=144 |issue=8 |pages=1659–66 |year=1999 |pmid=10486120| doi = 10.1007/s007050050620 }}</ref><ref name="pmid15183049">{{cite journal |author=de Villiers EM, Fauquet C, Broker TR, Bernard HU, zur Hausen H |title=Classification of papillomaviruses |journal=Virology |volume=324 |issue=1 |pages=17–27 |year=2004 |pmid=15183049 |doi=10.1016/j.virol.2004.03.033}}</ref> ====Baltimore Classification==== [[Image:Virus Baltimore Classification.svg|right|thumb|300px|The Baltimore Classification of viruses is based on the method of viral [[mRNA]] synthesis.]] {{Main|Baltimore classification}} The Baltimore classification of viruses is based on the mechanism of [[mRNA]] production. Viruses must generate positive strand mRNAs from their genomes to produce proteins and replicate themselves, but different mechanisms are used to achieve this in each virus family. Viral genomes may be single-stranded (ss) or double-stranded (ds), RNA or DNA, and may or may not use [[reverse transcriptase]] (RT). Additionally, ssRNA viruses be either [[sense (molecular biology)|sense]] (+) or antisense (-). This classification places viruses into seven groups: {{Baltimore groups}} As an example of viral classification, the [[chicken pox]] virus, ''[[Varicella zoster]]'' (VZV), belongs to family [[Herpesviridae]], subfamily [[Alphaherpesvirinae]] and genus ''[[Varicellovirus]]''. It remains unranked in terms of order. VZV is in Group I of the Baltimore Classification because it is a dsDNA virus that does not use reverse transcriptase. == Structure == A complete virus particle, known as a virion, consists of [[nucleic acid]] surrounded by a protective coat of [[protein]] called a [[capsid]]. Viruses can have a [[lipid]] "envelope" derived from the host [[cell membrane]]. A capsid is made from proteins encoded by the viral [[genome]] and its shape serves as the basis for [[morphology (biology)|morphological]] and antigenic distinction.<ref name="pmid14019094">{{cite journal |author=Caspar DL, Klug A |title=Physical principles in the construction of regular viruses |journal=Cold Spring Harb. Symp. Quant. Biol. |volume=27 |issue= |pages=1–24 |year=1962 |pmid=14019094 |doi= }}</ref><ref name="pmid13309339">{{cite journal |author=Crick FH, Watson JD |title=Structure of small viruses |journal=Nature |volume=177 |issue=4506 |pages=473–5 |year=1956 |pmid=13309339 | doi = 10.1038/177473a0 }}</ref> Virally coded protein subunits will self-assemble to form a capsid, generally requiring the presence of the virus genome. However, complex viruses code for proteins which assist in the construction of their capsid.<ref name="prescott" /> Proteins associated with nucleic acid are known as [[nucleoprotein]]s, and the association of viral capsid proteins with viral nucleic acid is called a nucleocapsid. In general, there are four main morphological virus types: {| cellpadding=3 cellspacing=0 border=1 style="border-collapse:collapse" |colspan=2 bgcolor="#dddddd"| '''Helical viruses''' |- | [[Image:Tobacco mosaic virus structure.png|center|thumb|200px|Diagram of a helical capsid]] | Helical capsids are composed of a single type of subunit stacked around a central axis to form a helical structure which may have a central cavity, or hollow tube. This arrangement results in rod-shaped or filamentous virions: these can be anything from short and highly rigid, to long and very flexible. The genetic material, generally single-stranded RNA, but ssDNA in some cases, is bound into the protein helix, by interactions between the negatively-charged nucleic acid and positive charges on the protein. Overall, the length of a helical capsid is related to the length of the nucleic acid contained within it and the diameter is dependent on the size and arrangement of protomers. The well-studied [[Tobacco mosaic virus]] is an example of a helical virus. |- |colspan=2 bgcolor="#dddddd"| '''Icosahedron viruses''' |- | [[Image:Enteric Adenoviruses.jpg|center|thumb|200px|Electron micrograph of icosahedral virions]] | Icosahedral capsid symmetry results in a spherical appearance of viruses at low magnification but actually consists of capsomers arranged in a regular geometrical pattern, similar to a [[football (soccer)|soccer ball]], hence they are not truly "spherical". Capsomers are ring shaped constructed from five to six copies of protomers. These associate via [[chemical bond|non-covalent bonding]] to enclose the viral nucleic acid, though generally less intimately than helical capsids, and may involve one or more protomers. Icosahedral architecture was employed by [[Buckminster Fuller|R. Buckminster Fuller]] in his [[geodesic dome]], and is the most efficient way of creating an enclosed robust structure from multiple copies of a single protein. The number of proteins required to form a spherical virus capsid is denoted by the T-number,<ref name="triang">{{Cite web |url=http://web.archive.org/web/20060223170529/http://rhino.bocklabs.wisc.edu/cgi-bin/virusworld/htdocs.pl?docname=triangulation.html |title=Virus triangulation numbers via Internet Archive|accessdate=2006-04-05}}</ref> where 60&times;''t'' proteins are necessary. In the case of the [[hepatitis B]] virus the T-number is 4, and 240 proteins assemble to form the capsid. |- |colspan=2 bgcolor="#dddddd"| '''Enveloped viruses ''' |- | [[Image:Varicella (Chickenpox) Virus PHIL 1878 lores.jpg|thumb|center|200px|Herpes zoster virus]] | Viruses are able to envelope themselves in a modified form of one of the [[cell membranes]] either the outer membrane surrounding an infected host cell, or from internal membranes such as nuclear membrane or endoplasmic reticulum, thus gaining an outer lipid bilayer known as a [[viral envelope]]. This membrane is studded with proteins coded for by the viral genome and host genome; however the lipid membrane itself and any carbohydrates present are entirely host-coded. The Influenza virus and HIV use this strategy. The viral envelope can give a virion a few distinct advantages over other capsid-only virions, such as protection from enzymes and certain chemicals. The proteins in it can include [[glycoprotein]]s functioning as [[receptor (biochemistry)|receptor molecules]], allowing host cells to recognize and bind these virions, resulting in the possible uptake of the virion into the cell. Most enveloped viruses are dependent on the envelope for infectivity. |- |colspan=2 bgcolor="#dddddd"| '''Complex viruses''' |- | [[Image:Tevenphage.svg|thumb|center|200px|Diagram of a bacteriophage]] | These viruses possess a capsid which is neither purely helical, nor purely icosahedral, and which may possess extra structures such as protein tails or a complex outer wall. Some [[bacteriophages]] have a complex structure consisting of an icosahedral head bound to a helical tail, the latter of which may have a hexagonal base plate with protruding protein tail fibres. |- | [[Image:Poxvirus.jpg|thumb|center|200px|Poxvirus]] |The [[Poxvirus]]es are large, complex viruses which have an unusual [[morphology (biology)|morphology]]. The viral genome is associated with proteins within a central disk structure known as a [[nucleoid]]. The nucleoid is surrounded by a membrane and two lateral bodies of unknown function. The virus has an outer envelope with a thick layer of protein studded over its surface. The whole particle is slightly [[pleiomorphic]], ranging from ovoid to brick shape.<ref>Long GW, Nobel J, Murphy FA, Herrmann KL, and Lourie B (1970) Experience with electron microscopy in the differential diagnosis of smallpox. Applied Microbiology 20(3):497-504.</ref> |} === Electron microscopy === {{details|Electron microscopy}} [[Image:Relative scale.svg|thumb|300px|right|The range of sizes shown by viruses, relative to those of other organisms and [[biomolecule]]s]] [[Electron microscopy]] is the most common method used to study the [[morphology (biology)|morphology]] of viruses. To increase the contrast between viruses and the background, electron-dense "stains" are used. These are solutions of salts of heavy metals such as [[tungsten]], that scatter the electrons from regions covered with the stain. When virus particles are coated with stain (positive staining), fine detail is obscured. [[Negative staining]] overcomes this problem by staining the background only.<ref name="pmid1715774">{{cite journal |author=Kiselev NA, Sherman MB, Tsuprun VL |title=Negative staining of proteins |journal=Electron Microsc. Rev. |volume=3 |issue=1 |pages=43–72 |year=1990 |pmid=1715774 |doi=}}</ref> === Size === A medium-sized virion next to a flea is roughly equivalent to a human next to a mountain twice the size of [[Mount Everest]]. Some [[filovirus]]es have a total length of up to 1400&nbsp;nm, however their capsid diameters are only about 80&nbsp;nm. Most viruses which have been studied have a [[capsid]] diameter between 10 and 300 [[nanometres]]. Most viruses are unable to be seen with a [[light microscope]] but some are as large or larger than the smallest bacteria and can be seen under high optical magnification. More commonly, both scanning and transmission [[electron microscope]]s are used to visualize virus particles. == Genome == {| class = "prettytable" style = "float:left; font-size:85%; margin-left:15px" |+ Genomic diversity among viruses ! Property || Parameters |- | ''Nucleic acid'' || *DNA *RNA *Both DNA and RNA |- | ''Shape'' || *Linear *Circular *Segmented |- | ''Strandedness'' || *Single-stranded *Double-stranded *Double-stranded with regions of single-strandedness |- | ''[[Sense (molecular biology)|Sense]]'' || *Positive sense (+) *Negative sense (-) *Ambisense (+/-) |} An enormous variety of genomic structures can be seen among viral species; as a group they contain more structural genomic diversity than the entire kingdoms of either plants, animals, or bacteria.<ref name="flint">{{cite book | title=Principles of Virology| edition=2nd edn |last=Flinth| coauthors=et al.| date=2004| publisher=ASM Press, New York| id=1-55581-259-7}}</ref> ===Nucleic acid=== A virus may employ either [[DNA]] or [[RNA]] as the nucleic acid. Rarely do they contain both, however [[cytomegalovirus]] is an exception to this, possessing a DNA core with several [[mRNA]] segments.<ref name="prescott" /> By far most viruses have RNA. Plant viruses tend to have single-stranded RNA and bacteriophages tend to have double-stranded DNA.<ref name="prescott" /> Some virus species possess abnormal [[nucleotide]]s, such as hydroxymethylcytosine instead of [[cytosine]], as a normal part of their genome.<ref name="prescott" /> ===Shape=== Viral genomes may be circular, such as [[polyomavirus]]es, or linear, such as [[adenovirus]]es. The type of nucleic acid is irrelevant to the shape of the genome. Among [[RNA virus]]es, the genome is often divided up into separate parts within the virion and are called ''segmented''. Double-stranded RNA genomes and some single-stranded RNA genomes are segmented.<ref name="prescott" /> Each segment often codes for one protein and they are usually found together in one capsid. Every segment is not required to be in the same virion for the overall virus to be infectious, as demonstrated by the [[brome mosaic virus]].<ref name="prescott" /> ===Strandedness=== A viral genome, irrespective of nucleic acid type, may be either single-stranded or double-stranded. Single-stranded genomes consist of an unpaired nucleic acid, analogous to one-half of a ladder split down the middle. Double-stranded genomes consist of two complementary paired nucleic acids, analogous to a ladder. Viruses, such as those belonging to the ''[[Hepadnaviridae]]'', contain a genome which is partially double-stranded and partially single-stranded.<ref name="flint" /> Viruses that infect humans include double-stranded RNA (e.g. [[Rotavirus]]), single-stranded RNA (e.g. [[Influenza virus]]), single-stranded DNA (e.g. [[Parvovirus B19]]) and double-stranded DNA ([[Herpesviridae|Herpes virus]]). ===Sense=== For viruses with RNA as their nucleic acid, the strands are said to be either [[positive-sense]] (called the plus-strand) or [[negative-sense]] (called the minus-strand), depending on whether it is complementary to viral mRNA. Positive-sense viral RNA is identical to viral mRNA and thus can be immediately [[translation (genetics)|translated]] by the host cell. Negative-sense viral RNA is complementary to mRNA and thus must be converted to positive-sense RNA by an [[RNA polymerase]] before translation. DNA nomenclature is similar to RNA nomenclature, in that the ''coding strand'' for the viral mRNA is complementary to it (-), and the ''non-coding strand'' is a copy of it (+). ===Genome size=== Genome size in terms of the weight of [[nucleotides]] varies between species. The smallest genomes code for only four proteins and weigh about 10<sup>6</sup> [[Atomic mass unit|Daltons]], the largest weigh about 10<sup>8</sup> Daltons and code for over one hundred proteins.<ref name="prescott" /> [[RNA virus]]es generally have smaller genome sizes than [[DNA virus]]es due to a higher error-rate when replicating, resulting in a maximum upper size limit. Beyond this limit, errors in the genome when replicating render the virus useless or uncompetitive. To compensate for this, RNA viruses often have segmented genomes where the genome is split into smaller molecules, thus reducing the chance of error.<ref>Pressing J, Reanney DC. Divided genomes and intrinsic noise.J Mol Evol. 1984;20(2):135-46.</ref> In contrast, DNA viruses generally have larger genomes due to the high fidelity of their replication enzymes.<ref name="flint" /> ===Gene reassortment=== There is an evolutionary advantage in having a segmented genome. Different strains of a virus with a segmented genome, from a pig or a bird or a human for example, such as [[Influenza virus]], can shuffle and combine with other genes producing progeny viruses or (offspring) that have unique characteristics. This is called reassortment or ''viral sex''.<ref> Goudsmit, Jaap. Viral Sex. Oxford Univ Press, 1998.ISBN-13: 9780195124965 ISBN-10: 0195124960</ref> This is one reason why Influenza virus constantly changes.<ref> Zhou NN, Senne DA, Landgraf JS, Swenson SL, Erickson G, Rossow K, Liu L, Yoon K, Krauss S, Webster RG. Genetic reassortment of avian, swine, and human influenza A viruses in American pigs.J Virol. 1999 Oct;73(10):8851-6.</ref> ===Genetic recombination=== [[Genetic recombination]] is the process by which a strand of DNA is broken and then joined to the end of a different DNA molecule. This can occur when viruses infect cells simultaneously and studies of viral evolution have shown that recombination has been rampant in the species studied.<ref name="pmid10573145">{{cite journal |author=Worobey M, Holmes EC |title=Evolutionary aspects of recombination in RNA viruses |journal=J. Gen. Virol. |volume=80 ( Pt 10) |issue= |pages=2535–43 |year=1999 |pmid=10573145 |doi=}}</ref> Recombination is common to both RNA and DNA viruses.<ref name="pmid15578739">{{cite journal |author=Lukashev AN |title=Role of recombination in evolution of enteroviruses |journal=Rev. Med. Virol. |volume=15 |issue=3 |pages=157–67 |year=2005 |pmid=15578739 |doi=10.1002/rmv.457}}</ref><ref name="pmid10479778">{{cite journal |author=Umene K |title=Mechanism and application of genetic recombination in herpesviruses |journal=Rev. Med. Virol. |volume=9 |issue=3 |pages=171–82 |year=1999 |pmid=10479778| doi = 10.1002/(SICI)1099-1654(199907/09)9:3<171::AID-RMV243>3.0.CO;2-A }}</ref> ===Genetic change=== Viruses undergo genetic change by several mechanisms. These include a process called [[genetic drift]] where individual bases in the DNA or RNA [[mutate]] to other bases. Most of these [[point mutations]] are silent in that they do not change the protein that the gene encodes, but others can confer evolutionary advantages such as resistance to [[antiviral drugs]].<ref>Pan XP, Li LJ, Du WB, Li MW, Cao HC, Sheng JF. Differences of YMDD mutational patterns, precore/core promoter mutations, serum HBV DNA levels in lamivudine-resistant hepatitis B genotypes B and C. J Viral Hepat. 2007 Nov;14(11):767-74.</ref> [[Antigenic shift]] is where there is a major change in the [[genome]] of the virus. This occurs as a result of [[Genetic recombination|recombination]] or [[reassortment]] (see above). When this happens with [[influenza]] viruses, [[pandemics]] may result.<ref>Hampson AW, Mackenzie JS. The influenza viruses.Med J Aust. 2006 Nov 20;185(10 Suppl):S39-43.</ref><ref>Nakajima K. The mechanism of antigenic shift and drift of human influenza virus Nippon Rinsho. 2003 Nov;61(11):1897-903.</ref> By genome rearrangement the structure of the gene changes although no mutations have necessarily occurred.<ref>Hundley F, McIntyre M, Clark B, Beards G, Wood D, Chrystie I, Desselberger U. Heterogeneity of genome rearrangements in rotaviruses isolated from a chronically infected immunodeficient child.J Virol. 1987 Nov;61(11):3365-72.</ref> RNA viruses are much more likely to mutate than DNA viruses for the reasons outlined above. Viruses often exist as [[quasispecies]] or swarms of viruses of the same species but with slightly different genome nucleoside sequences. Such quasispecies are a prime target for [[natural selection]].<ref>Metzner KJ. Detection and significance of minority quasispecies of drug-resistant HIV-1. HIV Ther. 2006 Dec;11(4):74-81.</ref> ==Replication== Viral populations do not grow through [[cell division]], because they are acellular; instead, they use the machinery and metabolism of a host cell to produce multiple copies of themselves. A virus can still cause degenerative effects within a cell without causing its death; collectively these are termed [[cytopathic effect]]s. ===Virus life cycle=== The [[viral life cycle|life cycle of viruses]] differs greatly between species (see below) but there are six ''basic'' stages in the life cycle of viruses: [[Image:Virus Replication.svg|right|thumb|250px|A virus attaches to the host cell and enters endocytosis. The capsid protein dissociates and the viral RNA is transported to the nucleus. In the nucleus, the viral polymerase complexes transcribe and replicate the RNA. Viral mRNAs migrate to cytoplasm where they are translated into protein. Then the newly synthesized virions [[viral shedding|bud]] from infected cell.]] *'''Attachment''' is a specific binding between viral capsid proteins and specific receptors on the host cellular surface. This specificity determines the host range of a virus. For example, the human immunodeficiency virus ([[HIV]]) infects only human [[T cells]], because its surface protein, [[gp120]], can interact with [[CD4]] and receptors on the T cell's surface. This mechanism has evolved to favour those viruses that only infect cells that they are capable of replicating in. Attachment to the receptor can induce the viral-envelope protein to undergo changes that results in the fusion of viral and cellular membranes. *'''Penetration''' follows attachment; viruses enter the host cell through receptor mediated [[endocytosis]] or membrane fusion. *'''Uncoating''' is a process in which the viral [[capsid]] is degraded by viral [[enzymes]] or host enzymes thus releasing the viral genomic nucleic acid. *'''Replication''' involves synthesis of viral messenger RNA ([[mRNA]]) for viruses except positive sense RNA viruses (see above), viral [[Protein biosynthesis|protein synthesis]] and assembly of viral proteins and viral genome replication. *Following the '''assembly''' of the virus particles post-translational modification of the viral proteins often occurs. In viruses such as [[HIV]], this modification, (sometimes called maturation), occurs ''after'' the virus has been released from the host cell.<ref name="pmid11451488">{{cite journal |author=Barman S, Ali A, Hui EK, Adhikary L, Nayak DP |title=Transport of viral proteins to the apical membranes and interaction of matrix protein with glycoproteins in the assembly of influenza viruses |journal=Virus Res. |volume=77 |issue=1 |pages=61–9 |year=2001 |pmid=11451488| doi = 10.1016/S0168-1702(01)00266-0 }}</ref> *Viruses are released from the host cell by lysis (see below). Enveloped viruses (e.g., HIV) typically are released from the host cell by [[viral shedding|budding]]. During this process, the virus acquires its phospholipid envelope which contains embedded viral glycoproteins. ====DNA viruses==== Animal [[DNA virus]]es, such as [[herpesvirus]]es, enter the host via [[endocytosis]], the process by which cells take in material from the external environment. Frequently after a chance collision with an appropriate surface receptor on a cell, the virus penetrates the cell, the viral genome is released from the capsid, and host polymerases begin transcribing viral mRNA. New virions are assembled and released either by cell lysis or by [[viral shedding|budding]] off the cell membrane. ====RNA viruses==== Animal [[RNA viruses]] can be placed into about four different groups depending on their modes of replication. The [[Sense (molecular biology)|polarity]] of the RNA largely determines the replicative mechanism, as well as whether the genetic material is single-stranded or double-stranded. Some [[RNA virus]]es are actually DNA-based but use an RNA-intermediate to replicate. RNA viruses are dependent on virally encoded [[RNA replicase]] to create copies of their genomes. ====Reverse transcribing viruses==== [[Reverse transcribing viruses]] replicate using reverse transcription, which is the formation of DNA from an RNA template. Reverse transcribing viruses containing RNA genomes use a DNA intermediate to replicate, whereas those containing DNA genomes use an RNA intermediate during genome replication. Both types use the [[reverse transcriptase]] enzyme to carry out the nucleic acid conversion. Both types are susceptible to [[antiviral drug]]s that inhibit the reverse transcriptase enzyme, e.g. [[zidovudine]] and [[lamivudine]]. An example of the first type is [[HIV]] which is a [[retrovirus]]. Retroviruses often integrate the DNA produced by [[reverse transcription]] into the host genome. Examples of the second type are the [[Hepadnaviridae]], which includes the [[Hepatitis B]] virus and the [[Caulimoviridae]] - e.g. [[Cauliflower mosaic virus]]. ====Bacteriophages==== {{Main|Bacteriophage}} [[Image:Phage.jpg|thumb|150px|right|Transmission electron micrograph of multiple [[bacteriophage]]s attached to a bacterial cell wall]] [[Bacteriophage]]s infect specific bacteria by binding to [[receptor (biochemistry)|surface receptor molecules]] and then enter the cell. Within a short amount of time, in some cases, just minutes, bacterial [[polymerase]] starts translating viral mRNA into protein. These proteins go on to become either new virions within the cell, helper proteins which help assembly of new virions, or proteins involved in cell [[lysis]]. Viral enzymes aid in the breakdown of the cell membrane, and in the case of the [[T4 phage]], in just over twenty minutes after injection over three hundred phages could be released. ====Viruses of Archaea==== Some viruses replicate within [[archaea]]: these are double-stranded [[DNA viruses]] that appear to be unrelated to any other form of virus and have a variety of unusual shapes, with some resembling bottles, hooked rods, or teardrops.<ref>{{cite journal |author=Prangishvili D, Forterre P, Garrett RA |title=Viruses of the Archaea: a unifying view |journal=Nat. Rev. Microbiol. |volume=4 |issue=11 |pages=837&ndash;48 |year=2006 |pmid=17041631 |doi=10.1038/nrmicro1527}}</ref> These viruses have been studied in most detail in the thermophilic archaea, particularly the orders Sulfolobales and Thermoproteales.<ref>{{cite journal |author=Prangishvili D, Garrett RA |title=Exceptionally diverse morphotypes and genomes of crenarchaeal hyperthermophilic viruses |journal=Biochem. Soc. Trans. |volume=32 |issue=Pt 2 |pages=204&ndash;8 |year=2004 |pmid=15046572 |url=http://www.biochemsoctrans.org/bst/032/0204/bst0320204.htm |doi=10.1042/BST0320204}}</ref> Defenses against these viruses may involve [[RNA interference]] from [[repetitive DNA]] sequences within archaean genomes that are related to the genes of the viruses.<ref>{{cite journal |author=Mojica FJ, Díez-Villaseñor C, García-Martínez J, Soria E |title=Intervening sequences of regularly spaced prokaryotic repeats derive from foreign genetic elements |journal=J. Mol. Evol. |volume=60 |issue=2 |pages=174&ndash;82 |year=2005 |pmid=15791728 |doi=10.1007/s00239-004-0046-3}}</ref><ref>{{cite journal |author=Makarova KS, Grishin NV, Shabalina SA, Wolf YI, Koonin EV |title=A putative RNA-interference-based immune system in prokaryotes: computational analysis of the predicted enzymatic machinery, functional analogies with eukaryotic RNAi, and hypothetical mechanisms of action |journal=Biol. Direct |volume=1 |pages=7 |year=2006 |pmid=16545108 |doi=10.1186/1745-6150-1-7}}</ref> ==Lifeform debate== Viruses have been described as "organisms at the edge of life",<ref>Rybicki ''ibid''</ref> but argument continues over whether viruses are truly alive. According to the [[United States Code]], they are considered [[microorganism]]s in the sense of [[biological weaponry]] and malicious use. Scientists, however, are divided. Things become more complicated as they look at [[viroids]] and [[prions]]. Viruses resemble other organisms in that they possess genes and can evolve in infected cells by [[natural selection]].<ref>Holmes EC.PLoS Biol. 2007 Oct 2;5(10):e278. Viral Evolution in the Genomic Age</ref><ref>Shackelton LA, Holmes EC.Phylogenetic evidence for the rapid evolution of human B19 erythrovirus.J Virol. 2006 Apr;80(7):3666-9.</ref> They can reproduce by creating multiple copies of themselves through self-assembly. Viruses do not have a [[cell (biology)|cell]] structure (regarded as the basic unit of life), although they do have genes. Additionally, although they reproduce, they do not self-metabolize and require a host cell to replicate and synthesize new products. However, bacterial species such as [[Rickettsia]] and [[Chlamydia (bacterium)|Chlamydia]] are considered living organisms but are unable to reproduce outside a host cell. An argument can be made that accepted forms of life use [[cell division]] to reproduce, whereas viruses spontaneously assemble within cells. The comparison is drawn between viral self-assembly and the autonomous growth of non-living [[crystallization|crystals]]. Virus self-assembly within host cells has implications for the study of the [[origin of life]], as it lends credence to the hypothesis that life could have started as self-assembling organic molecules.<ref>Vlassov, Alexander V. (Jul 2005). "The RNA World on Ice: A New Scenario for the Emergence of RNA Information". Journal of Molecular Evolution 61: 264-273. </ref> If viruses are considered alive, then the criteria specifying life will have to exclude the cell. If viruses are said to be alive, the question could follow of whether even smaller infectious particles, such as [[viroid]]s and [[prion]]s, are alive. ===Notable examples=== {{See|Table of clinically important viruses}} The clinically most notable<ref name=Microbiology354-366> {{cite book |author=Fisher, Bruce; Harvey, Richard P.; Champe, Pamela C. |title=Lippincott's Illustrated Reviews: Microbiology (Lippincott's Illustrated Reviews Series) |publisher=Lippincott Williams & Wilkins |location=Hagerstwon, MD |year= |pages= |isbn=0-7817-8215-5 |oclc= |doi=}} Pages 354-366 </ref> virus species belong to the following families: <div class="references-small" style="-moz-column-count:3; column-count:3;"> *[[Adenoviridae]] *[[Picornaviridae]] *[[Herpesviridae]] *[[Hepadnaviridae]] *[[Flaviviridae]] *[[Retroviridae]] *[[Orthomyxoviridae]] *[[Paramyxoviridae]] *[[Papovaviridae]] *[[Rhabdoviridae]] *[[Reoviridae]] *[[Togaviridae]] </div> {| class="wikitable" |- |+ Comparison table of clinically important virus families and species |- ! Family ! [[Baltimore classification|Baltimore group]] ! Important species<ref name=Microbiology354-366Unless> Unless else specified in boxes, the ref is: {{cite book |author=Fisher, Bruce; Harvey, Richard P.; Champe, Pamela C. |title=Lippincott's Illustrated Reviews: Microbiology (Lippincott's Illustrated Reviews Series) |publisher=Lippincott Williams & Wilkins |location=Hagerstwon, MD |year= |pages= |isbn=0-7817-8215-5 |oclc= |doi=}} Pages 354-366 </ref> ! [[Viral envelope|envelopment]]<ref name=Microbiology354-366Unless/> ! Virion shape<ref name=Microbiology354-366Unless/> ! Replication site<ref name=Microbiology354-366Unless/> |- | [[Adenoviridae]] | [[dsDNA virus|dsDNA]] | ''adenovirus'' | non-enveloped | icosahedral | nucleus |- | [[Picornaviridae]] | [[positive-sense ssRNA virus|+ssRNA]] | [[coxsackievirus]], [[hepatitis a virus]], [[poliovirus]] | non-enveloped | icosahedral |- | [[Herpesviridae]] | [[dsDNA virus|dsDNA]] | [[epstein-barr virus]], [[Herpes simplex virus|herpes simplex virus, type 1 and 2]], [[human cytomegalovirus]], [[Kaposi's sarcoma-associated herpesvirus|human herpesvirus, type 8]], [[varicella zoster virus]] | enveloped | | nucleus |- | [[Hepadnaviridae]] | [[dsDNA virus|dsDNA]] and [[ssDNA virus|ssDNA]] | [[hepatitis B virus]] | enveloped | icosahedral | nucleus |- | [[Flaviviridae]] | [[positive-sense ssRNA virus|+ssRNA]] | [[hepatitis C virus]] | enveloped | icosahedral |- | [[Retroviridae]] | [[positive-sense ssRNA virus|+ssRNA]] | [[human immunodeficiency virus]] (HIV) | enveloped |- | [[Orthomyxoviridae]] | [[negative-sense ssRNA virus|-ssRNA]] | [[influenza virus]] | enveloped | spherical | nucleus<ref name=Microbiology315> {{cite book |author=Fisher, Bruce; Harvey, Richard P.; Champe, Pamela C. |title=Lippincott's Illustrated Reviews: Microbiology (Lippincott's Illustrated Reviews Series) |publisher=Lippincott Williams &amp; Wilkins |location=Hagerstwon, MD |year= |pages= |isbn=0-7817-8215-5 |oclc= |doi=}} Page 315 </ref> |- | [[Paramyxoviridae]] | [[negative-sense ssRNA virus|-ssRNA]] | [[measles virus]], [[mumps virus]], [[parainfluenza virus]], [[respiratory syncytial virus]] | enveloped | spherical |- | [[Papovaviridae]] | [[ssDNA virus|ssDNA]] | [[papillomavirus]] | non-enveloped | icosahedral |- | [[Rhabdoviridae]] | [[negative-sense ssRNA virus|-ssRNA]] | [[rabies virus]] | enveloped | helical, bullet shaped |- | [[Reoviridae]] | [[double-stranded RNA|dsRNA]] | [[Rotavirus]] | non-enveloped | icosahedral | cytoplasm |- | [[Togaviridae]] | [[positive-sense ssRNA virus|+ssRNA]] | [[Rubella virus]] | enveloped | icosahedral |- |} ==Viruses and disease== :''For more examples of diseases caused by viruses see [[List of infectious diseases]]. Examples of common human diseases caused by viruses include the [[common cold]], [[influenza|the flu]], [[chickenpox]] and [[cold sores]]. Serious diseases such as [[Ebola]], [[AIDS]], [[avian influenza]] and [[SARS]] are caused by viruses. The relative ability of viruses to cause disease is described in terms of [[virulence]]. Other diseases are under investigation as to whether they too have a virus as the causative agent, such as the possible connection between [[Human Herpesvirus Six]] (HHV6) and neurological diseases such as [[multiple sclerosis]] and [[chronic fatigue syndrome]]. There is current controversy over whether the [[borna virus]], previously thought of as causing [[neurology|neurological]] diseases in horses, could be responsible for [[psychiatry|psychiatric]] illnesses in humans.<ref name=Chen_1999>{{cite journal |author=Chen C, Chiu Y, Wei F, Koong F, Liu H, Shaw C, Hwu H, Hsiao K |title=High seroprevalence of Borna virus infection in schizophrenic patients, family members and mental health workers in Taiwan |journal=Mol Psychiatry |volume=4 |issue=1 |pages=33–8 |year=1999 |pmid=10089006 | doi = 10.1038/sj.mp.4000484 }}</ref> Viruses have different mechanisms by which they produce disease in an organism, which largely depends on the species. Mechanisms at the cellular level primarily include cell [[lysis]], the breaking open and subsequent death of the cell. In [[multicellular organism]]s, if enough cells die the whole organism will start to suffer the effects. Although viruses cause disruption of healthy [[homeostasis]], resulting in disease, they may exist relatively harmlessly within an organism. An example would include the ability of the [[herpes simplex virus]], which cause cold sores, to remain in a dormant state within the human body. This is called latency<ref>Margolis TP, Elfman FL, Leib D, Pakpour N, Apakupakul K, Imai Y, Voytek C. Spontaneous reactivation of herpes simplex virus type 1 in latently infected murine sensory Ganglia.J Virol. 2007 Oct;81(20):11069-74. Epub 2007 Aug 8.</ref> and is a characteristic of the [[herpes viruses]] including the [[Epstein-Barr virus]], which causes glandular fever, and the [[Varicella zoster]] virus, which causes [[chicken pox]]. Latent chickenpox infections return in later life as the disease called [[shingles]]. Some viruses can cause life-long or [[Chronic (medical)|chronic]] infections, where the viruses continue to replicate in the body despite the hosts' defense mechanisms.<ref name="pmid17931183">{{cite journal |author=Bertoletti A, Gehring A |title=Immune response and tolerance during chronic hepatitis B virus infection |journal=Hepatol. Res. |volume=37 Suppl 3 |issue= |pages=S331–8 |year=2007 |pmid=17931183 |doi=10.1111/j.1872-034X.2007.00221.x }}</ref> This is common in [[Hepatitis B virus]] and [[Hepatitis C Virus]] infections. People chronically infected with the Hepatitis B virus are known as carriers who serve as reservoirs of infectious virus. In some populations, with a high proportion of carriers, the disease is said to be [[Endemic (epidemiology)|endemic]].<ref name="pmid17645465">{{cite journal |author=Nguyen VT, McLaws ML, Dore GJ |title=Highly endemic hepatitis B infection in rural Vietnam |journal=Journal of Gastroenterology and Hepatology |volume=22 |issue= | pages = 2093 |year=2007 |pmid=17645465 |doi=10.1111/j.1440-1746.2007.05010.x }}</ref> When diagnosing Hepatitis B virus infections, it is important to distinguish between [[Acute (medical)|acute]] and [[Chronic (medical)|chronic]] infections.<ref name="pmid17664817">{{cite journal |author=Rodrigues C, Deshmukh M, Jacob T, Nukala R, Menon S, Mehta A |title=Significance of HBV DNA by PCR over serological markers of HBV in acute and chronic patients |journal=Indian journal of medical microbiology |volume=19 |issue=3 |pages=141–4 |year=2001 |pmid=17664817 |doi=}}</ref> ===Epidemiology=== Viral [[epidemiology]] is the branch of medical science dealing with the transmission and control of virus infections in humans. Transmission of viruses can be vertical, that is from mother to child, or horizontal, which means from person to person. Examples of [[vertical transmission]] include [[Hepatitis B virus]] and [[HIV]] where the baby is born already infected with the virus.<ref name="pmid17825648">{{cite journal |author=Fowler MG, Lampe MA, Jamieson DJ, Kourtis AP, Rogers MF |title=Reducing the risk of mother-to-child human immunodeficiency virus transmission: past successes, current progress and challenges, and future directions |journal=Am. J. Obstet. Gynecol. |volume=197 |issue=3 Suppl |pages=S3–9 |year=2007 |pmid=17825648 |doi=10.1016/j.ajog.2007.06.048}}</ref> Another, more rare, example is the [[Varicella zoster virus]], which although causing relatively mild infections in humans, can be fatal to the foetus and newly born baby.<ref name="pmid11190597">{{cite journal |author=Sauerbrei A, Wutzler P |title=The congenital varicella syndrome |journal=Journal of perinatology : official journal of the California Perinatal Association |volume=20 |issue=8 Pt 1 |pages=548–54 |year=2000 |pmid=11190597 |doi=}}</ref> [[Horizontal transmission]] is the most common mechanism of spread of viruses in populations. Transmission can be exchange of blood by sexual activity, e.g. [[HIV]], [[Hepatitis B]] and [[Hepatitis C]]; by mouth by exchange of [[saliva]], e.g. [[Epstein-Barr virus]], or from contaminated food or water, e.g. [[Norovirus]]; by breathing in viruses in the form of [[aerosol]]s, e.g. [[Influenza virus]]; and by insect vectors such as mosquitoes, e.g. [[dengue]]. The rate or speed of transmission of viral infections depends on factors that include [[population density]], the number of susceptible individuals, (i.e. those who are not immune),<ref> Garnett GP. Role of herd immunity in determining the effect of vaccines against sexually transmitted disease.J Infect Dis. 2005 Feb 1;191 Suppl 1:S97-106.</ref> the quality of health care and the weather.<ref name="pmid16544901">{{cite journal |author=Platonov AE |title= (The influence of weather conditions on the epidemiology of vector-borne diseases by the example of West Nile fever in Russia) |language=Russian |journal=Vestn. Akad. Med. Nauk SSSR |volume= |issue=2 |pages=25–9 |year=2006 |pmid=16544901 |doi=}}</ref> === Epidemics and pandemics === {{details|List of epidemics}} [[Image:Reconstructed Spanish Flu Virus.jpg|thumb|250px|right|The reconstructed [[1918 influenza]] virus]] [[Indigenous peoples of the Americas|Native American]] populations were devastated by contagious diseases, particularly [[smallpox]], brought to the Americas by European colonists. It is unclear how many Native Americans were killed by foreign diseases after the arrival of Columbus in the Americas, but the numbers have been estimated to be close to 70% of the indigenous population. The damage done by this disease significantly aided European attempts to displace and conquer the native population.<ref>Ranlet P. The British, the Indians, and smallpox: what actually happened at Fort Pitt in 1763? Pa Hist. 2000;67(3):427-41.</ref><ref>Van Rijn K. "Lo! The poor Indian!" colonial responses to the 1862-63 smallpox epidemic inBritish Columbia and Vancouver Island.Can Bull Med Hist. 2006;23(2):541-60.</ref><ref>Patterson KB, Runge T. Smallpox and the Native American.Am J Med Sci. 2002 Apr;323(4):216-22.</ref><ref>Sessa R, Palagiano C, Scifoni MG, di Pietro M, Del Piano M. The major epidemic infections: a gift from the Old World to the New? Panminerva Med. 1999 Mar;41(1):78-84.</ref><ref>Bianchine PJ, Russo TA. The role of epidemic infectious diseases in the discovery of America. Allergy Proc. 1992 Sep-Oct;13(5):225-32.</ref><ref>Hauptman LM. Smallpox and American Indian; Depopulation in Colonial New York. N Y State J Med. 1979 Nov;79(12):1945-9.</ref><ref>Fortuine R. Smallpox decimates the Tlingit (1787). Alaska Med. 1988 May-Jun;30(3):109.</ref> {{main|Spanish flu}} A [[pandemic]] is a world-wide epidemic. The 1918 flu pandemic, commonly referred to as the [[Spanish flu]], was a [[Pandemic Severity Index|category 5]] influenza pandemic caused by an unusually severe and deadly [[Influenza A virus]]. The victims were often healthy young adults, in contrast to most influenza outbreaks which predominantly affect juvenile, elderly, or otherwise weakened patients. <br />The [[Spanish flu]] pandemic lasted from 1918 to 1919. Older estimates say it killed 40–50 million people,<ref name=Patterson1>{{cite journal | last =Patterson | first = KD | coauthors = Pyle GF | title=The geography and mortality of the 1918 influenza pandemic | journal= Bull Hist Med. | year=1991 | month=Spring | volume=65 | issue=1 | pages = 4–21 | pmid = 2021692}}</ref> while more recent research suggests that it may have killed as many as 100 million people, or 5% of the world's population in 1918.<ref>Johnson, Niall P. A. S. and Mueller, Juergen, "Updating the Accounts: Global Mortality of the 1918–1920 'Spanish' Influenza Pandemic," Bulletin of the History of Medicine 76 (2002), pp. 105–115.</ref> {{main|AIDS}} [[Image:Ebola Virus TEM PHIL 1832 lores.jpg|thumb|250px|right|The [[Ebola]] virus]] Most researchers believe that HIV originated in [[sub-Saharan Africa]] during the [[twentieth century]];<ref name=Gao> {{ cite journal | author=Gao, F., Bailes, E., Robertson, D. L., Chen, Y., Rodenburg, C. M., Michael, S. F., Cummins, L. B., Arthur, L. O., Peeters, M., Shaw, G. M., Sharp, P. M. and Hahn, B. H. | title=Origin of HIV-1 in the Chimpanzee Pan troglodytes troglodytes | journal=Nature | year=1999 | pages=436&ndash;441 | volume=397 | issue=6718 | pmid=9989410 {{doi|10.1038/17130}} | doi=10.1038/17130 }}</ref> it is now a [[pandemic]], with an estimated 38.6 [[million]] people now living with the disease worldwide.<ref name=UNAIDS2006>{{ cite book | author =[[UNAIDS]] | year = 2006 | title = 2006 Report on the global AIDS epidemic | chapter = Overview of the global AIDS epidemic | chapterurl = http://data.unaids.org/pub/GlobalReport/2006/2006_GR_CH02_en.pdf | accessdate = 2006-06-08 | format= PDF }}</ref> As of January 2006, the [[Joint United Nations Programme on HIV/AIDS]] (UNAIDS) and the [[World Health Organization]] (WHO) estimate that AIDS has killed more than 25 million people since it was first recognized on [[June 5]], [[1981]], making it one of the most destructive [[epidemic]]s in [[recorded history]].<ref> Mawar N, Saha S, Pandit A, Mahajan U. The third phase of HIV pandemic: social consequences of HIV/AIDS stigma & discrimination & future needs.Indian J Med Res. 2005 Dec;122(6):471-84. Review.</ref> [[Image:Marburg virus.jpg|thumb|250px|right|The [[Marburg virus]]]] {{main|Ebola}} Several highly lethal viral pathogens are members of the [[Filoviridae]]. Filoviruses are filament-like viruses that cause [[viral hemorrhagic fever]], and include the [[Ebola]] and [[Marburg virus]]es. The Marburg virus attracted widespread press attention in April 2005 for an outbreak in [[Angola]]. Beginning in October 2004 and continuing into 2005, the outbreak was the world's worst epidemic of any kind of viral hemorrhagic fever.<ref>Towner JS, Khristova ML, Sealy TK, Vincent MJ, Erickson BR, Bawiec DA, HartmanAL, Comer JA, Zaki SR, Stroher U, Gomes da Silva F, del Castillo F, Rollin PE,Ksiazek TG, Nichol ST. Marburgvirus genomics and association with a large hemorrhagic fever outbreak in Angola.J Virol. 2006 Jul;80(13):6497-516.</ref> === Viruses and cancer === {{details|Oncovirus}} [[Image:Leukemia cells that contain Epstein Barrvirus using a FA staining technique PHIL 2984 lores.jpg|right|thumb|250px|Human leukaemia cells infected by the [[Epstein Barr virus]]]] Viruses are an established cause of [[malignancy]] in humans and other species. The main viruses associated with human cancers are [[human papillomavirus]], [[hepatitis B]] and [[hepatitis C]] virus, [[Epstein-Barr virus]], and [[human T-lymphotropic virus]]. Hepatitis viruses, including [[hepatitis B]] and [[hepatitis C]], can induce a [[Chronic (medical)|chronic]] viral infection that leads to [[Hepatocellular carcinoma|liver cancer]].<ref> {{cite journal |author=Koike K |title=Hepatitis C virus contributes to hepatocarcinogenesis by modulating metabolic and intracellular signalling pathways |journal=J. Gastroenterol. Hepatol. |volume=22 Suppl 1 |issue= |pages=S108–11 |year=2007 |pmid=17567457 |doi=10.1111/j.1440-1746.2006.04669.x}}</ref><ref> {{cite journal |author=Hu J, Ludgate L |title=HIV-HBV and HIV-HCV coinfection and liver cancer development |journal=Cancer Treat. Res. |volume=133 |issue= |pages=241–52 |year=2007 |pmid=17672044 |doi=}} </ref> Infection by [[human T-lymphotropic virus]] can lead to [[tropical spastic paraparesis]] and [[adult T-cell leukemia]].<ref> {{cite journal |author=Bellon M, Nicot C |title=Telomerase: a crucial player in HTLV-I-induced human T-cell leukemia |journal=Cancer genomics & proteomics |volume=4 |issue=1 |pages=21–5 |year=2007 |pmid=17726237 |doi=}}</ref> [[Human papillomaviruses]] are an established cause of cancers of [[cervix]], skin, [[anus]], and [[penis]].<ref> {{cite journal |author=Schiffman M, Castle PE, Jeronimo J, Rodriguez AC, Wacholder S |title=Human papillomavirus and cervical cancer |journal=Lancet |volume=370 |issue=9590 |pages=890–907 |year=2007 |pmid=17826171 |doi=10.1016/S0140-6736(07)61416-0}}</ref> Within the [[Herpesviridae]], [[Kaposi's sarcoma-associated herpesvirus]] causes [[Kaposi's sarcoma]] and body cavity lymphoma, and [[Epstein–Barr virus]] causes [[Burkitt's lymphoma]], [[Hodgkin’s lymphoma]], [[B cell|B]] [[Lymphoproliferative disorders|lymphoproliferative disorder]] and [[nasopharyngeal carcinoma]].<ref> {{cite journal |author=Klein E, Kis LL, Klein G |title=Epstein-Barr virus infection in humans: from harmless to life endangering virus-lymphocyte interactions |journal=Oncogene |volume=26 |issue=9 |pages=1297–305 |year=2007 |pmid=17322915 |doi=10.1038/sj.onc.1210240}}</ref> ===Laboratory diagnosis=== [[Image:CPE rounding.jpg|right|thumb|250px|Cells infected with [[Herpes simplex virus]]. The rounding of the cells, their detachment from the cell sheet is the typical cytopathic effect produced by this virus.]] {{Main|Laboratory diagnosis of virus}} In the diagnostic laboratory, virus infections are confirmed by several methods that include: *Growth of the virus in a [[cell culture]] from a specimen taken from the patient. *Detection of virus-specific [[IgM]] antibody (see below) in the blood. *Detection of virus antigens by [[ELISA]] in tissues and fluids. *Detection of virus encoded DNA and RNA by [[PCR]]. *Observation of virus particles by [[electron microscopy]]. === Prevention and treatment === Because viruses use the machinery of a host cell to reproduce and reside within them, they are difficult to eliminate without killing the host cell. The most effective [[medicine|medical]] approaches to viral diseases so far are [[vaccination]]s to provide resistance to infection, and [[antiviral drugs]] which treat the symptoms of viral infections. ===Host immune response=== The body's first line of defense against viruses is the [[innate immune system]]. This comprises cells and other mechanisms that defend the host from infection in a non-specific manner. This means that the cells of the innate system recognize, and respond to, pathogens in a generic way, but unlike the [[adaptive immune system]], it does not confer long-lasting or protective immunity to the host.<ref name=Alberts>{{cite book | last = Alberts| first = Bruce| coauthors = Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts, and Peter Walters | title = Molecular Biology of the Cell; Fourth Edition | publisher = Garland Science| date = 2002 | location = New York and London | url = http://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowTOC&rid=mboc4.TOC&depth=2 | id = ISBN 0-8153-3218-1}}</ref> [[RNA interference]] is an important innate defense against viruses.<ref>Ding SW, Voinnet O. Antiviral immunity directed by small RNAs. Cell. 2007 Aug 10;130(3):413-26.</ref> Many viruses have a replication strategy that involves double-stranded RNA [[dsRNA]]. When such a virus infects a cell, it releases its RNA molecule or molecules, which immediately bind to a protein complex called [[Dicer]] that cuts the RNA into smaller pieces. A biochemical pathway called the RISC complex is activated which degrades the viral [[mRNA]] and the cell survives the infection. Rotaviruses avoid this mechanism by not uncoating fully inside the cell and by releasing newly produced mRNA through pores in the particle's inner capsid. The genomic [[dsRNA]] remains protected inside the core of the virion.<ref name="pmid15579070">{{cite journal |author=Patton JT, Vasquez-Del Carpio R, Spencer E |title=Replication and transcription of the rotavirus genome |journal=Curr. Pharm. Des. |volume=10 |issue=30 |pages=3769–77 |year=2004 |pmid=15579070| doi = 10.2174/1381612043382620 }}</ref><ref name="pmid15010218">{{cite journal |author=Jayaram H, Estes MK, Prasad BV |title=Emerging themes in rotavirus cell entry, genome organization, transcription and replication |journal=Virus Res. |volume=101 |issue=1 |pages=67–81 |year=2004 |pmid=15010218 |doi=10.1016/j.virusres.2003.12.007}}</ref> When the [[adaptive immune system]] of a [[vertebrate]] encounters a virus, it produces specific [[antibodies]] which bind to the virus and render it non-infectious. This is called [[humoral immunity]]. Two types of antibodies are important. The first called [[IgM]] is highly effective at neutralizing viruses but is only produced by the cells of the immune system for a few weeks. The second, called, [[IgG]] is produced indefinitely. The presence of IgM in the blood of the host is used to test for acute infection, whereas IgG indicates an infection sometime in the past.<ref>Greer S, Alexander GJ. Viral serology and detection. Baillieres Clin Gastroenterol. 1995 Dec;9(4):689-721</ref> Both types of antibodies are measured when tests for [[Immunity (medical)|immunity]] are carried out.<ref>Laurence JC. Hepatitis A and B immunizations of individuals infected with humanimmunodeficiency virus.Am J Med. 2005 Oct;118 Suppl 10A:75S-83S.</ref> A second defense of vertebrates against viruses is called [[cell-mediated immunity]] and involves immune cells known as [[T cells]]. The body's cells constantly display short fragments of their proteins on the cell's surface, and if a T cell recognizes a suspicious viral fragment there, the host cell is destroyed by ''T killer'' cells and the virus-specific T-cells proliferate. Cells such as the [[macrophage]] are specialists at this [[antigen presentation]].<ref>Cascalho M, Platt JL. Novel functions of B cells.Crit Rev Immunol. 2007;27(2):141-51.</ref><ref>Khatri M, Sharma JM. Modulation of macrophages by infectious bursal disease virus.Cytogenet Genome Res. 2007;117(1-4):388-93</ref> Not all virus infections produce a protective immune response in this way. HIV evades the immune system by constantly changing the amino acid sequence of the proteins on the surface of the virion. These persistent viruses evade immune control by sequestration, blockade of [[antigen presentation]], [[cytokine]] resistance, evasion of [[natural killer cell]] activities, escape from [[apoptosis]], and [[antigenic shift]].<ref>Hilleman MR. Strategies and mechanisms for host and pathogen survival in acute and persistent viral infections. Proc Natl Acad Sci U S A. 2004 Oct 5;101 Suppl 2:14560-6. Epub 2004 Aug 5.</ref> Other viruses, called "[[neurotropic virus]]es", are disseminated by neural spread where the [[immune system]] may be unable to reach them. The production of [[interferon]] is an important host defense mechanism.<ref>Le Page C, Genin P, Baines MG, Hiscott J. Interferon activation and innate immunity.Rev Immunogenet. 2000;2(3):374-86.</ref> ===Vaccines=== {{details|Vaccination}} [[Vaccination]] is a cheap and effective way of preventing infections by viruses. Vaccines were used to prevent viral infections long before the discovery of the actual viruses. Their use has resulted in a dramatic decline in morbidity (illness) and mortality (death) associated with viral infections such as [[polio]], [[measles]], [[mumps]] and [[rubella]].<ref name="pmid17068034">{{cite journal |author=Asaria P, MacMahon E |title=Measles in the United Kingdom: can we eradicate it by 2010? |journal=BMJ |volume=333 |issue=7574 |pages=890–5 |year=2006 |pmid=17068034 |doi=10.1136/bmj.38989.445845.7C}}</ref> [[Smallpox]] infections have been eradicated.<ref name="pmid16989262">{{cite journal |author=Lane JM |title=Mass vaccination and surveillance/containment in the eradication of smallpox |journal=Curr. Top. Microbiol. Immunol. |volume=304 |issue= |pages=17–29 |year=2006 |pmid=16989262 |doi=}}</ref> Currently vaccines are available to prevent over thirteen viral infections of humans,<ref name="pmid16364754">{{cite journal |author=Arvin AM, Greenberg HB |title=New viral vaccines |journal=Virology |volume=344 |issue=1 |pages=240–9 |year=2006 |pmid=16364754 |doi=10.1016/j.virol.2005.09.057}}</ref> and more are used to prevent viral infections of animals.<ref name="pmid17892169">{{cite journal |author=Pastoret PP, Schudel AA, Lombard M |title=Conclusions--future trends in veterinary vaccinology |journal=Rev. - Off. Int. Epizoot. |volume=26 |issue=2 |pages=489–94, 495–501, 503–9 |year=2007 |pmid=17892169 |doi=}}</ref> Vaccines can consist of live-attenuated or killed viruses, or viral proteins ([[antigens]]).<ref name="pmid16494719">{{cite journal |author=Palese P |title=Making better influenza virus vaccines? |journal=Emerging Infect. Dis. |volume=12 |issue=1 |pages=61–5 |year=2006 |pmid=16494719 |doi=}}</ref> Live vaccines contain weakened forms of the virus that causes the disease. Such viruses are called attenuated. Live vaccines can be dangerous when given to people with a weak immunity, (who are described as [[immunocompromised]]), because in these people, the weakened virus can cause the original disease.<ref name="pmid1090805">{{cite journal |author=Thomssen R |title=Live attenuated versus killed virus vaccines |journal=Monographs in allergy |volume=9 |issue= |pages=155–76 |year=1975 |pmid=1090805 |doi=}}</ref> Biotechnology and genetic engineering techniques are used to produce subunit vaccines. These vaccines use only the [[capsid]] proteins of the virus. [[Hepatitis B]] vaccine is an example of this type of vaccine.<ref name="pmid3018891">{{cite journal |author=McLean AA |title=Development of vaccines against hepatitis A and hepatitis B |journal=Rev. Infect. Dis. |volume=8 |issue=4 |pages=591–8 |year=1986 |pmid=3018891 |doi=}}</ref> Subunit vaccines are safe for [[immunocompromised]] patients because they cannot cause the disease.<ref name="pmid16221073">{{cite journal |author=Casswall TH, Fischler B |title=Vaccination of the immunocompromised child |journal=Expert review of vaccines |volume=4 |issue=5 |pages=725–38 |year=2005 |pmid=16221073 |doi=10.1586/14760584.4.5.725}}</ref> The Yellow Fever virus vaccine, a live-attenuated strain called 17D, is arguably the safest and most effective vaccine ever generated. ===Antiviral drugs=== {{details|Antiviral drug}} [[Image:DT chemical structure.png|left|thumb|100px|The true DNA base [[thymidine]]]] [[Image:Zidovudine.svg|right|thumb|100px|The antiviral drug [[Zidovudine]] - [[AZT]]]] Over the past twenty years, the development of [[antiviral drug]]s has increased rapidly. This has been driven by the AIDS epidemic. Antiviral drugs are often [[nucleoside analogues]], (fake DNA building blocks), which viruses incorporate into their genomes during replication. The life-cycle of the virus is then halted because the newly synthesized DNA is inactive. This is because these analogues lack the [[hydroxyl groups]] which along with [[phosphorus]] atoms, link together to form the strong "backbone" of the DNA molecule. This is called DNA [[chain termination]].<ref name="pmid15592828">{{cite journal |author=Magden J, Kääriäinen L, Ahola T |title=Inhibitors of virus replication: recent developments and prospects |journal=Appl. Microbiol. Biotechnol. |volume=66 |issue=6 |pages=612–21 |year=2005 |pmid=15592828 |doi=10.1007/s00253-004-1783-3}}</ref> Examples of nucleoside analogues are [[aciclovir]] for [[Herpesviridae|Herpes virus]] infections and [[lamivudine]] for [[HIV]] and [[Hepatitis B]] virus infections. [[Aciclovir]] is one of the oldest and most frequently prescribed antiviral drugs.<ref name="pmid6355051">{{cite journal |author=Mindel A, Sutherland S |title=Genital herpes - the disease and its treatment including intravenous acyclovir |journal=J. Antimicrob. Chemother. |volume=12 Suppl B |issue= |pages=51–9 |year=1983 |pmid=6355051 |doi=}}</ref> [[Image:G chemical structure.png|left|thumb|100px|[[Guanosine]]]][[Image:Aciclovir.svg|right|thumb|100px|The guanosine analogue [[Aciclovir]]]] Other antiviral drugs in use target different stages of the viral life cycle. [[HIV]] is dependent on a proteolytic enzyme called the [[HIV-1 protease]] for it to become fully infectious. There is a class of drugs called [[protease inhibitors]] which have been designed to inactivate the enzyme. [[Hepatitis C]] is caused by an [[RNA]] virus. In 80% of people infected, the disease is [[Chronic (medical)|chronic]], and without treatment, they are [[infected]] and [[infectious]] for the remainder of their lives. However, there is now an effective treatment using the nucleoside analogue drug [[ribavirin]] combined with [[interferon]].<ref>Witthoft T, Moller B, Wiedmann KH, Mauss S, Link R, Lohmeyer J, Lafrenz M,Gelbmann CM, Huppe D, Niederau C, Alshuth U. Safety, tolerability and efficacy of peginterferon alpha-2a and ribavirin in chronic hepatitis C in clinical practice: The German Open Safety Trial. J Viral Hepat. 2007 Nov;14(11):788-96.</ref> The treatment of chronic [[Asymptomatic carrier|carriers]] of the [[Hepatitis B]] virus by using a similar strategy using [[lamivudine]] is being developed.<ref>Rudin D, Shah SM, Kiss A, Wetz RV, Sottile VM. Interferon and lamivudine vs. interferon for hepatitis B e antigen-positive hepatitis B treatment: meta-analysis of randomized controlled trials.Liver Int. 2007 Nov;27(9):1185-93.</ref> ==Applications== ===Life sciences and medicine=== Viruses are important to the study of [[molecular biology|molecular]] and [[cellular biology]] as they provide simple systems that can be used to manipulate and investigate the functions of cells. The study and use of viruses have provided valuable information about aspects of cell biology. For example, viruses have been useful in the study of [[genetics]] and helped our understanding of the basic mechanisms of [[molecular genetics]], such as [[DNA replication]], [[transcription (genetics)|transcription]], [[RNA processing]], [[translation (genetics)|translation]], [[protein]] transport, and [[immunology]]. [[Image:Gene therapy.jpg|right|thumb|250px|[[Gene therapy]] using an [[Adenovirus]] vector]] [[genetics|Geneticists]] often use viruses as [[vector (biology)|vectors]] to introduce genes into cells that they are studying. This is useful for making the cell produce a foreign substance, or to study the effect of introducing a new gene into the genome. In similar fashion, [[virotherapy]] uses viruses as vectors to treat various diseases, as they can specifically target cells and DNA. It shows promising use in the treatment of cancer and in [[gene therapy]]. Eastern European scientists have used [[phage therapy]] as an alternative to antibiotics for some time, and interest in this approach is increasing, due to the high level of [[antibiotic resistance]] now found in some pathogenic bacteria.<ref name="pmid16258815">{{cite journal |author=Matsuzaki S, Rashel M, Uchiyama J, ''et al'' |title=Bacteriophage therapy: a revitalized therapy against bacterial infectious diseases |journal=J. Infect. Chemother. |volume=11 |issue=5 |pages=211–9 |year=2005 |pmid=16258815 |doi=10.1007/s10156-005-0408-9}}</ref> Granulosis (GV) and nucleo-polyhedrosis viruses (NPV) may also be used as [[biological insecticides]] (''e.g''. [[Cydia pomonella granulosis virus|''Cydia pomonella'' granulovirus]]). ===Materials science and nanotechnology=== Current trends in nanotechnology promise to make much more versatile use of viruses. From the viewpoint of a materials scientist, viruses can be regarded as organic nanoparticles.<ref> Proceedings of SPIE -- Volume 6413Smart Materials IV, Nicolas H. Voelcker, Editor, 64130F (Dec. 22, 2006). Hybrid organic-inorganic nanoparticles: controlled incorporation of gold nanoparticles into virus-like particles and application in surface-enhanced Raman spectroscopy Marcus Niebert, James Riches, Mark Howes, Charles Ferguson, Robert G. Parton, Anton P. J. Middelberg, Llew Rintoul, and Peter M. Fredericks.Queensland Univ. of Technology (Australia) (published online Dec. 22, 2006)</ref> Their surface carries specific tools designed to cross the barriers of their host cells. The size and shape of viruses, and the number and nature of the functional groups on their surface, is precisely defined. As such, viruses are commonly used in materials science as scaffolds for covalently linked surface modifications. A particular quality of viruses is that they can be tailored by directed evolution. The powerful techniques developed by life sciences are becoming the basis of engineering approaches towards nanomaterials, opening a wide range of applications far beyond biology and medicine.<ref name=fischlechner>{{cite journal |author=Fischlechner M, Donath E |title=Viruses as Building Blocks for Materials and Devices |doi=10.1002/anie.200603445 |journal=Angewandte Chemie International Edition |volume=46 |issue= |pages=3184 |year=2007}}</ref> Because of their size, shape, and well-defined chemical structures, viruses have been used as templates for organizing materials on the nanoscale. Recent examples include work at the [[Naval Research Laboratory]] in [[Washington, DC]], using Cowpea Mosaic Virus ([[CPMV]]) particles to amplify signals in [[microarray]] based sensors. In this application, the virus particles separate the [[fluorescence|fluorescent]] [[dye]]s used for signaling in order to prevent the formation of non-fluorescent [[dimer]]s that act as [[Quenching (fluorescence)|quenchers]].<ref>''Fluorescent signal amplification of carbocyanine dyes using engineered viral nanoparticles.'' Carissa M. Soto, Amy Szuchmacher Blum, Nikolai Lebedev, Gary J. Vora, Carolyn E. Meador, Angela P. Won, Anju Chatterji, John E. Johnson, and Banahalli R. Ratna, ''Journal of the American Chemical Society'', '''128''', 5184 (2006). </ref> Another example is the use of CPMV as a nanoscale breadboard for molecular electronics.<ref>An Engineered Virus as a Scaffold for Three-Dimensional Self-Assembly on the Nanoscale. Amy Szuchmacher Blum, Carissa M. Soto, Charmaine D. Wilson, Tina L. Brower, Steven K. Pollack, Terence L. Schull, Anju Chatterji, Tianwei Lin, John E. Johnson, Christian Amsinck, Paul Franzon, Ranganathan Shashidhar and Banahalli Ratna, ''Small'', '''7,''' 702 (2005).</ref> In April 2006, scientists at the [[Massachusetts Institute of Technology]] (MIT) created [[nanotechnology|nanoscale]] metallic wires using a [[Genetic engineering|genetically-modified]] virus.<ref name="mitvirusbattery">{{Cite web |url=http://web.mit.edu/newsoffice/2006/virus-battery.html |title=Researchers build tiny batteries with viruses|accessdate=2007-04-05|publisher=MIT News Office}}</ref> The MIT team was able to use the virus to create a working [[Battery (electricity)|battery]] with an [[energy density]] up to three times more than current materials. The potential exists for this technology to be used in [[liquid crystal]]s, [[solar cell]]s, [[fuel cells]], and other electronics in the future. ===Weapons=== {{details|Biological warfare}} The ability of viruses to cause devastating [[epidemic]]s in human societies has led to the concern that viruses could be weaponised for [[biological warfare]]. Further concern was raised by the successful recreation of the infamous 1918 influenza virus in a laboratory.<ref name="cdcnews">{{Cite web |url=http://www.cdc.gov/OD/OC/MEDIA/pressrel/r051005.htm |title=Researchers Reconstruct 1918 Pandemic Influenza Virus; Effort Designed to Advance Preparedness|accessdate=2007-04-05|publisher=Centers for Disease Control}}</ref> The [[smallpox]] virus devastated numerous societies throughout history before its eradication. It currently exists in several secure laboratories in the world, and fears that it may be used as a weapon are not totally unfounded. The vaccine for smallpox is not safe, and during the years before the eradication of smallpox disease more people became seriously ill as a result of vaccination than did people from smallpox<ref name="pmid12911836">{{cite journal |author=Aragón TJ, Ulrich S, Fernyak S, Rutherford GW |title=Risks of serious complications and death from smallpox vaccination: a systematic review of the United States experience, 1963-1968 |journal=BMC public health |volume=3 |issue= |pages=26 |year=2003 |pmid=12911836 |doi=10.1186/1471-2458-3-26}}</ref> and smallpox vaccination is no longer universally practiced.<ref name="pmid15578369">{{cite journal |author=Weiss MM, Weiss PD, Mathisen G, Guze P |title=Rethinking smallpox |journal=Clin. Infect. Dis. |volume=39 |issue=11 |pages=1668–73 |year=2004 |pmid=15578369 |doi=10.1086/425745}}</ref> Thus, the modern global human population has almost no established resistance to smallpox; if it were to be released, a massive loss of life could be sustained before the virus is brought under control. ==Electron micrographs of viruses== <gallery> Image:Norwalk.jpg|[[Norovirus]]. This RNA virus causes winter vomiting disease. It is often in the news as a cause of gastro-enteritis on cruise ships and in hospitals. Image:Caliciviruses2.jpg|Caliciviruses are related to Noroviruses. Image:Human Torovirus.jpg|Torovirus. An enveloped RNA virus. Image:Coronaviruses 004 lores.jpg|Coronaviruses are a group of viruses that have a halo, or crown-like (corona) appearance when viewed under a microscope. Image:Ebola virus em.png|Ebola Virus is a filamentous RNA virus. Image:Measles virus.JPG|[[Measles]] virus. This is called a ''thin section'' where the virus particle has been cut in two. Image:Respiratory syncytial virus 01.jpg|[[Respiratory Syncytial Virus]] (RSV). In this preparation the ribonucleoprotein can be seen as a herring bone pattern. Image:Parvovirus in Blood.jpg|[[Parvovirus B19]]. Parvovirus B19 is a small DNA virus best known for causing a childhood exanthema called fifth disease or erythema infectiosum. Image:Papilloma Virus (HPV) EM.jpg|[[Human Papilloma Virus]] Image:EM of influenza virus.jpg|[[Influenza virus]] Image:Herpes simplex virus TEM B82-0474 lores.jpg|Transmission electron micrograph of [[Herpes]] virus an enveloped virus that looks like fried eggs by negative stain electron microscopy. Image:Polio EM PHIL 1875 lores.PNG|[[Transmission electron microscopy|TEM]] [[micrograph]] of [[Poliovirus]] virions. </gallery> ==See also== *[[Virology]] *[[Influenza]] *[[Rotavirus]] *[[Herpes simplex virus]] *[[Hepatitis B virus]] *[[Satellite (biology)|Satellite]] * [[Neurotropic virus]] *[[Bacteriophages]] (bacterial viruses) {{Viruses}} ==References== {{Reflist|2}} [[Category:Virology|*]] [[Category:Viruses|Viruses]] [[Category:Microbiology]] {{Link FA|ja}} {{Link FA|te}} [[af:Virus]] [[als:Virus (Medizin)]] [[ar:فيروس]] [[zh-min-nan:Pēⁿ-to̍k]] [[bs:Virus (biologija)]] [[bg:Вирус]] [[ca:Virus]] [[cs:Virus]] [[cy:Feirws]] [[da:Virus (biologi)]] [[de:Viren]] [[et:Viirused]] [[el:Ιός]] [[es:Virus]] [[eo:Viruso (biologio)]] [[eu:Birus]] [[fa:ویروس]] [[fo:Virus]] [[fr:Virus]] [[ga:Víreas]] [[ko:바이러스]] [[hi:वायरस]] [[hr:Virusi (biologija)]] [[id:Virus]] [[is:Veira]] [[it:Virus (biologia)]] [[he:נגיף]] [[ka:ვირუსები]] [[la:Virus biologicum]] [[lv:Vīruss]] [[lt:Virusas]] [[hu:Vírus]] [[mk:Вирус]] [[mr:विषाणू]] [[ms:Virus]] [[mn:Вирус]] [[nl:Virus (biologie)]] [[ja:ウイルス]] [[no:Virus]] [[nn:Virus]] [[oc:Virus]] [[pam:Virus]] [[pl:Wirusy]] [[pt:Vírus]] [[ro:Virus]] [[qu:Añaw]] [[ru:Вирусы]] [[simple:Virus]] [[sk:Vírus]] [[sl:Virusi]] [[sr:Вирус]] [[su:Virus]] [[fi:Virukset]] [[sv:Virus]] [[ta:தீ நுண்மம்]] [[te:వైరస్]] [[th:ไวรัส]] [[vi:Virus]] [[tr:Virüs]] [[uk:Вірус]] [[ur:حُمہ]] [[wa:virûsse]] [[yi:ווירוס]] [[zh:病毒]]