Virology
32772
225861482
2008-07-15T19:13:41Z
ClueBot
4928500
Reverting possible vandalism by [[Special:Contributions/207.80.104.200|207.80.104.200]] to version by Quicksilvre. False positive? [[User:ClueBot/FalsePositives|Report it]]. Thanks, [[User:ClueBot]]. (440917) (Bot)
'''Virology''', often considered a part of [[microbiology]] or of [[pathology]], is the study of [[virus (biology)|biological viruses and virus-like agents]]: their structure, classification and evolution, their ways to infect and exploit [[cell (biology)|cells]] for virus reproduction, the diseases they cause, the techniques to isolate and culture them, and their potential uses in research and therapy.
== Virus structure and classification ==
A major branch of virology is [[virus classification]]. Viruses can be classified according to the host cell they infect: animal viruses, [[plant virus]]es, [[fungus|fungal]] viruses, and [[bacteriophage]]s (viruses infecting [[bacteria]], which include the most complex viruses). Another classification uses the geometrical shape of their [[capsid]] (often a [[helix]] or an [[icosahedron]]) or the virus's structure (e.g. presence or absence of a [[lipid]] [[viral envelope|envelope]]). Viruses range in size from about [[1 E-8 m|30 nm]] to about [[1 E-7 m|450 nm]], which means that most of them cannot be seen with [[light microscope]]s. The shape and structure of viruses can be studied with [[electron microscope|electron microscopy]], with [[NMR spectroscopy]], and most importantly with [[X-ray crystallography]].
The most useful and most widely used classification system distinguishes viruses according to the type of [[nucleic acid]] they use as genetic material and the [[viral replication]] method they employ to coax host cells into producing more viruses:
* [[DNA virus]]es (divided into [[DsDNA virus|double-stranded DNA viruses]] and the much less common [[SsDNA virus|single-stranded DNA viruses]]),
* [[RNA virus]]es (divided into [[positive-sense ssRNA virus|positive-sense single-stranded RNA viruses]], [[negative-sense ssRNA virus|negative-sense single-stranded RNA viruses]] and the much less common [[DsRNA virus|double-stranded RNA viruses]]),
* [[reverse transcriptase|reverse transcribing]] viruses ([[dsDNA-RT virus|double-stranded reverse-transcribing DNA viruses]] and [[ssRNA-RT virus|single-stranded reverse-transcribing RNA viruses]] including [[retrovirus]]es).
In addition virologists also study ''subviral particles'', infectious entities even smaller than viruses: [[viroid]]s (naked circular RNA molecules infecting plants), [[satellite (biology)|satellites]] (nucleic acid molecules with or without a capsid that require a helper virus for infection and reproduction), and [[prion]]s ([[protein]]s that can exist in a pathological conformation that induces other prion molecules to assume that same conformation).
The latest report by the [[International Committee on Taxonomy of Viruses]] (2005) lists 5450 viruses, organized in over 2,000 species, 287 genera, 73 families and 3 orders.
The [[taxon|taxa]] in virology are not necessarily [[monophyletic]]. In fact, the evolutionary relationships of the various virus groups remain unclear, and three hypotheses regarding their origin exist:
# Viruses arose from non-living matter, separately from and in parallel to other life forms, possibly in the form of self-reproducing [[RNA]] [[ribozyme]]s similar to [[viroid]]s.
# Viruses arose from earlier, more competent cellular life forms that became parasites to host cells and subsequently lost most of their functionality; examples of such tiny parasitic prokaryotes are [[Mycoplasma]] and [[Nanoarchaeum|Nanoarchaea]].
# Viruses arose as parts of the genome of cells, most likely [[transposon]]s or [[plasmid]]s, that acquired the ability to "break free" from the host cell and infect other cells.
It is of course possible that different alternatives apply to different virus groups.
Of particular interest here is [[mimivirus]], a giant virus that infects [[amoebozoa|amoebae]] and carries much of the molecular machinery traditionally associated with bacteria. Is it a simplified version of a parasitic prokaryote, or did it originate as a simpler virus that acquired genes from its host?
The evolution of viruses, which often occurs in concert with the evolution of their hosts, is studied in the field of [[viral evolution]].
While viruses reproduce and evolve, they don't engage in [[metabolism]] and depend on a host cell for reproduction. The often-debated question of whether they are alive or not is a matter of definition that does not affect the biological reality of viruses.
== Viral diseases and host defenses==
One main motivation for the study of viruses is the fact that they cause many important infectious diseases, among them the [[common cold]], [[influenza]], [[rabies]], [[measles]], many forms of [[diarrhea]], [[hepatitis]], [[yellow fever]], [[poliomyelitis|polio]], [[smallpox]] and [[AIDS]]. Some viruses, known as [[oncovirus]]es, contribute to certain forms of [[cancer]]; the best studied example is the association between [[Human papillomavirus]] and [[cervical cancer]]. Some subviral particles also cause disease: [[Kuru (disease)|Kuru]] and [[Creutzfeldt-Jakob disease]] are caused by prions, and [[hepatitis D]] is due to a satellite virus.
The study of the manner in which viruses cause disease is [[viral pathogenesis]]. The degree to which a virus causes disease is its [[virulence]].
When the [[immune system]] of a [[vertebrate]] encounters a virus, it produces specific [[antibody|antibodies]] which bind to the virus and mark it for destruction. The presence of these antibodies is often used to determine whether a person has been exposed to a given virus in the past, with tests such as [[ELISA]]. [[Vaccination]]s protect against viral diseases, in part, by eliciting the production of antibodies. Specifically constructed [[monoclonal antibodies]] can also be used to detect the presence of viruses, with a technique called [[fluorescence microscopy]].
A second defense of vertebrates against viruses, [[cell-mediated immunity]], involves [[immune cell]]s known as [[T cell]]s: 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 and the virus-specific T-cells proliferate. This mechanism is jump-started by certain vaccinations.
[[RNA interference]], an important cellular mechanism found in plants, animals and many other [[eukaryote]]s, most likely evolved as a defense against viruses. An elaborate machinery of interacting enzymes detects double-stranded RNA molecules (which occur as part of the life cycle of many viruses) and then proceeds to destroy all single-stranded versions of those detected RNA molecules.
Every lethal viral disease presents a paradox: killing its host is obviously of no benefit to the virus, so how and why did it evolve to do so? Today it is believed that most viruses are relatively benign in their natural hosts; the lethal viral diseases are explained as resulting from an "accidental" jump of the virus from a species in which it is benign to a new one that is not accustomed to it (see [[zoonosis]]). For example, serious influenza viruses probably have pigs or birds as their natural host, and [[HIV]] is thought to derive from the benign monkey virus [[SIV]].
While it has been possible to prevent (certain) viral diseases by vaccination for a long time, the development of [[antiviral drug]]s to ''treat'' viral diseases is a comparatively recent development. The first such drug was [[interferon]], a substance that is naturally produced by certain immune cells when an infection is detected and stimulates other parts of the immune system.
== Molecular biology research and viral therapy ==
[[Bacteriophage]]s, the viruses which infect [[bacteria]], can be relatively easily grown as [[viral plaque]]s on [[microbiological culture|bacterial cultures]]. Bacteriophages occasionally move genetic material from one bacterial cell to another in a process known as [[transduction (genetics)|transduction]], and this [[horizontal gene transfer]] is one reason why they served as a major research tool in the early development of [[molecular biology]]. The [[genetic code]], the function of [[ribozyme]]s, the first [[recombinant DNA]] and early [[library (biology)|genetic libraries]] were all arrived at using bacteriophages. Certain genetic elements derived from viruses, such as highly effective [[promoter]]s, are commonly used in molecular biology research today.
Growing animal viruses outside of the living host animal is more difficult. Classically, fertilized chicken eggs have often been used, but [[cell culture]]s are increasingly employed for this purpose today.
Since viruses that infect [[eukaryote]]s need to transport their genetic material into the host cell's [[cell nucleus|nucleus]], they are attractive tools for introducing new genes into the host (known as [[transformation (genetics)|transformation]] or [[transfection]]). Modified retroviruses are often used for this purpose, as they integrate their genes into the host's [[chromosome]]s.
This approach of using viruses as gene vectors is being pursued in the [[gene therapy]] of genetic diseases. An obvious problem to be overcome in viral gene therapy is the rejection of the transforming virus by the immune system.
[[Phage therapy]], the use of bacteriophages to combat bacterial diseases, was a popular research topic before the advent of [[antibiotics]] and has recently seen renewed interest.
[[Oncolytic virus]]es are viruses that preferably infect [[cancer]] cells. While early efforts to employ these viruses in the therapy of cancer failed, there have been reports in 2005 and 2006 of encouraging preliminary results.<ref>[http://www.isracast.com/tech_news/260106_tech.aspx Viruses: The new cancer hunters], IsraCast, 1 March 2006</ref>
==Other uses of viruses==
:''See: [[Virus#Materials science and nanotechnology|Materials science and nanotechnology]]''
A new application of genetically engineered viruses in [[nanotechnology]] was recently described.
==History==
A very early form of vaccination known as [[variolation]] was developed several thousand years ago in China. It involved the application of materials from [[smallpox]] sufferers in order to immunize others. In 1717 [[Lady Mary Wortley Montagu]] observed the practice in [[Istanbul]] and attempted to popularize it in Britain, but encountered considerable resistance. In 1796 [[Edward Jenner]] developed a much safer method, using [[cowpox]] to successfully immunize a young boy against smallpox, and this practice was widely adopted. Vaccinations against other viral diseases followed, including the successful [[rabies]] vaccination by [[Louis Pasteur]] in 1886. The nature of viruses however was not clear to these researchers.
In 1892 [[Dimitri Ivanovski]] showed that a disease of [[tobacco|tobacco plants]], [[tobacco mosaic virus|tobacco mosaic disease]], could be transmitted by extracts that were passed through filters fine enough to exclude even the smallest known bacteria. In 1898 [[Martinus Beijerinck]], also working on tobacco plants, found that this "filterable agent" grew in the host and was thus not a mere [[toxin]]. The question of whether the agent was a "living fluid" or a particle was however still open.
In 1903 it was suggested for the first time that transduction by viruses might cause cancer. Such an oncovirus in chickens was described by [[Francis Peyton Rous]] in 1911; it was later called [[Rous sarcoma virus]] 1 and understood to be a retrovirus. Several other cancer-causing retroviruses have since been described.
The existence of viruses that infect bacteria was first recognized by [[Frederick Twort]] in 1911, and, independently, by [[Felix d'Herelle]] in 1917. Since bacteria could be grown easily in culture, this led to an explosion of virology research. An important investigator in this area, [[Max Delbrück]], described the basic life cycle of a virus in 1937: rather than "growing", a virus particle is assembled from its constituent pieces in one step; eventually it leaves the host cell to infect other cells. The [[Hershey-Chase experiment]] in 1952 showed that only DNA and not protein enters a bacterial cell upon infection with [[enterobacteria phage T2|bacteriophage T2]]. [[transduction (genetics)|Transduction]] of bacteria by bacteriophages was first described in the same year.
While plant viruses and bacteriophages can be grown comparatively easily, animal viruses normally require a living host animal, which complicates their study immensely. In 1931 it was shown that [[influenza virus]] could be grown in fertilized chicken eggs, a method that is still used today to produce vaccines. In 1937, [[Max Theiler]] managed to grow the yellow fever virus in chicken eggs and produced a vaccine from an attenuated virus strain; this vaccine saved millions of lives and is still being used today.
In 1949 [[John F. Enders]], [[Thomas Weller]] and [[Frederick Robbins]] reported that they had been able to grow [[poliovirus]] in cultured human embryonal cells, the first significant example of an animal virus grown outside of animals and chicken eggs. This work aided [[Jonas Salk]] in deriving a polio vaccine from killed polio viruses; this vaccine was shown to be effective in 1955.
The first virus which could be [[crystal]]ized and whose structure could therefore be elucidated in detail was [[tobacco mosaic virus]] (TMV), the virus that had been studied earlier by Ivanovski and Beijerink. In 1935, [[Wendell Meredith Stanley|Wendell Stanley]] achieved its crystallization for [[electron microscope|electron microscopy]] and showed that it remains active even after crystallization. Clear [[X-ray diffraction]] pictures of the crystallized virus were obtained by Bernal and Fankuchen in 1941. Based on such pictures, [[Rosalind Franklin]] proposed the full structure of the tobacco mosaic virus in 1955. Also in 1955, [[Heinz Fraenkel-Conrat]] and [[Robley Williams]] showed that purified TMV [[RNA]] and its [[capsid]] (coat) protein can assemble by themselves to form functional viruses, suggesting that this simple mechanism is likely the natural assembly mechanism within the host cell.
In 1963, the [[Hepatitis B|Hepatitis B virus]] was discovered by [[Baruch Blumberg]] who went on to construct a vaccine against Hepatitis B.
In 1965, [[Howard Temin]] described the first [[retrovirus]]: an RNA-virus that was able to insert its genome in the form of DNA into the host's genome. [[Reverse transcriptase]], the key enzyme that retroviruses use to translate their RNA into DNA, was first described in 1970, independently by Howard Temin and [[David Baltimore]]. The first retrovirus infecting [[human]]s was identified by [[Robert Gallo]] in 1974. Later <!-- when, by whom? --> it was found that reverse transcriptase is not specific to retroviruses; [[retrotransposon]]s which code for reverse transcriptase are abundant in the genomes of all eukaryotes. About 10-40% of the human genome derives from such retrotransposons.
In 1975 the functioning of oncoviruses was clarified considerably. Until that time, it was thought that these viruses carried certain genes called [[oncogene]]s which, when inserted into the host's genome, would cause cancer. [[J. Michael Bishop|Michael Bishop]] and [[Harold Varmus]] showed that the oncogene of Rous sarcoma virus is in fact not specific to the virus but is contained in healthy animals of many species. The oncovirus can switch this pre-existing benign proto-oncogene on, turning it into a true oncogene.
1976 saw the first recorded outbreak of [[Ebola hemorrhagic fever]], a highly lethal virally transmitted disease.
In 1977, [[Frederick Sanger]] achieved the first complete sequencing of the [[genome]] of any organism, the bacteriophage [[Phi X 174]]. In the same year, [[Richard J. Roberts|Richard Roberts]] and [[Phillip Allen Sharp|Phillip Sharp]] independently showed that the genes of [[adenovirus]] contain [[intron]]s and therefore require [[gene splicing]]. It was later realized that almost all genes of eukaryotes have introns as well.
A world-wide vaccination campaign lead by the UN [[World Health Organization]] lead to the eradication of [[smallpox]] in 1979.
In 1982, [[Stanley Prusiner]] discovered [[prion]]s and showed that they cause [[scrapie]].
The first cases of AIDS were reported in 1981, and [[HIV]], the retrovirus causing it, was identified in 1983 by [[Robert Gallo]] and [[Luc Montagnier]]. Tests detecting HIV infection by detecting the presence of HIV antibody were developed. Subsequent tremendous research efforts turned HIV into the best studied virus. [[Kaposi's sarcoma-associated herpesvirus|Human Herpes Virus 8]], the cause of [[Kaposi's sarcoma]] which is often seen in AIDS patients, was identified in 1994. Several anti-retroviral drugs were developed in the late 1990s, decreasing AIDS mortality dramatically in developed countries.
The [[Hepatitis C virus]] was identified using novel [[molecular cloning]] techniques in 1987, leading to screening tests that dramatically reduced the incidence of post-[[blood transfusion|transfusion]] [[hepatitis]].<ref>[http://www.laskerfoundation.org/awards/library/2000c_cit.shtml 2000 Albert Lasker Award for Clinical Medical Research], The Lasker Foundation. Accessed 20 February 2008</ref>
The first attempts at [[gene therapy]] involving viral vectors began in the early 1980s, when retroviruses were developed that could insert a foreign gene into the host's genome. They contained the foreign gene but did not contain the viral genome and therefore could not reproduce. Tests in mice were followed by tests in [[human]]s, beginning in 1989. The first human studies attempted to correct the genetic disease [[severe combined immunodeficiency]] (SCID), but clinical success was limited. In the period from 1990 to 1995, gene therapy was tried on several other diseases and with different viral vectors, but it became clear that the initially high expectations were overstated. In 1999 a further setback occurred when 18-year-old [[Jesse Gelsinger]] died in a gene therapy trial. He suffered a severe immune response after having received an [[adenovirus]] vector. Success in the gene therapy of two cases of X-linked [[Severe combined immunodeficiency|SCID]] was reported in 2000.<ref>Zeger Debyser. [http://www.ohsu.edu/nod/documents/week1/short.vectorology.pdf A Short Course on Virology / Vectorology / Gene Therapy], ''Current Gene Therapy'', 2003, 3, 495-499</ref>
In 2002 it was reported that [[poliovirus]] had been synthetically assembled in the laboratory, representing the first synthetic organism. Assembling the 7741-base genome from scratch, starting with the virus's published RNA sequence, took about two years. In 2003 a faster method was shown to assemble the 5386-base genome of the bacteriophage [[Phi X 174]] in 2 weeks.
The giant [[mimivirus]], in some sense an intermediate between tiny prokaryotes and ordinary viruses, was described in 2003 and [[DNA sequencing|sequenced]] in 2004.
The strain of [[Influenza A virus subtype H1N1]] that killed up to 50 million people during the [[Spanish flu]] pandemic in 1918 was reconstructed in 2005. Sequence information was pieced together from preserved tissue samples of flu victims; viable virus was then synthesized from this sequence.<ref>{{Cite news
| issn = 0362-4331
| last = Kolata
| first = Gina
| title = Experts Unlock Clues to Spread of 1918 Flu Virus
| work = The New York Times
| accessdate = 2008-02-03
| date = 2005-10-06
| url = http://www.nytimes.com/2005/10/06/health/06flu.html?pagewanted=2
}}</ref>
Two vaccines protecting against several [[cervical cancer]]-causing strands of [[human papillomavirus]] (HPV) were released in 2006.
In 2006 and 2007 it was reported that introducing a small number of specific [[transcription factor]] genes into normal skin cells of mice or [[human]]s can turn these cells into [[pluripotency|pluripotent]] [[stem cell]]s, known as [[Induced Pluripotent Stem Cell]]s. The technique uses modified retroviruses to transform the cells; this is a potential problem for human therapy since these viruses integrate their genes at a random location in the host's genome, which can interrupt other genes and potentially causes cancer.<ref>[http://www.sciam.com/article.cfm?id=stem-cells-without-cancer Stem Cells—This Time without the Cancer], Scientific American News, 30 November 2007</ref>
==See also==
*[[Introduction to virus]]
*[[Virus (biology)|Virus]]
*[[Virus classification]]
*[[List of viruses]]
*[[Animal virology]]
*[[:Category:Viral diseases]]
*[[List of infectious diseases#Viral infectious diseases|List of viral diseases]]
*[[List of publications in biology#Virology|Important publications in virology]]
*[[Wikipedia:WikiProject Viruses]]
==References==
{{reflist}}
<small>
*Villarreal, L. P. (2005) ''Viruses and the Evolution of Life''. ASM Press, Washington DC ISBN 1-55581-309-7
* Samuel Baron (ed.) (1996) ''Medical Microbiology'', 4th ed., [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mmed.part.5437 Section 2: Virology] (freely searchable online book)
* Coffin, Hughes, Varmus. (1997) ''[http://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowTOC&rid=rv.TOC&depth=10 Retroviruses]'' (freely searchable online book)
</small>
== External links and sources ==
* David Sander: [http://www.virology.net/ All the Virology on the WWW] - collection of links, pictures, lecture notes
* [http://media.med.sc.edu/microbiology2007/ Online lectures in virology] University of South Carolina
* [http://www.microbiologybytes.com/introduction/introduction.html MicrobiologyBytes: Origins of Virology]
* [http://www.microbiologybytes.com/tutorials/Time/Machine.html MicrobiologyBytes: The Virology Time Machine]
* [http://medicine.wustl.edu/~virology/timeline.htm Timeline of the history of virology], from the [[Washington University in St. Louis]].
* [http://virology-online.com Wong's Virology].
* [http://www.vrc.nih.gov Vaccine Research Center (VRC)] - Information concerning vaccine research studies
[[Category:Virology| ]]
[[Category:Microbiology]]
[[ar:علم الفيروسات]]
[[ca:Virologia]]
[[cs:Virologie]]
[[co:Virologia]]
[[de:Virologie]]
[[es:Virología]]
[[fr:Virologie]]
[[id:Virologi]]
[[is:Veirufræði]]
[[it:Virologia]]
[[he:וירולוגיה]]
[[la:Virologia]]
[[ms:Virologi]]
[[nl:Virologie]]
[[ja:ウイルス学]]
[[nn:Virologi]]
[[oc:Virologia]]
[[pl:Wirusologia]]
[[pt:Virologia]]
[[ro:Virusologie]]
[[ru:Вирусология]]
[[sk:Virológia]]
[[sv:Virologi]]
[[tl:Birolohiya]]
[[th:ไวรัสวิทยา]]
[[tr:Viroloji]]
[[uk:Вірусологія]]