Orthomyxoviridae
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2008-07-01T13:26:22Z
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{{Taxobox
| name = Orthomyxoviridae
| virus_group = v
| familia = '''''Orthomyxoviridae'''''
| subdivision_ranks = Genera
| subdivision = ''[[Influenzavirus A]]''<br>
''[[Influenzavirus B]]''<br>
''[[Influenzavirus C]]''<br>
''[[Isavirus]]''<br>
''[[Thogotovirus]]
}}
{{Flu}}
The '''''Orthomyxoviridae''''' (Derivation of name: ''orthos'' is Greek for straight; ''myxa'' is Greek for [[mucus]])<ref> [http://www.ncbi.nlm.nih.gov/ICTVdb/Ictv/fs_ortho.htm International Committee on Taxonomy of Viruses] Index of Viruses - Orthomyxoviridae (2006). In: ICTVdB - The Universal Virus Database, version 4. Büchen-Osmond, C (Ed), Columbia University, New York, USA.</ref> are a family of [[RNA virus]]es that includes five [[genus|genera]]: [[Influenzavirus A]], [[Influenzavirus B]], [[Influenzavirus C]], [[Thogotovirus]] and [[Isavirus]]. The first three genera contain viruses that cause [[influenza]] in vertebrates, including [[bird]]s (see also [[avian influenza]]), [[human]]s, and other [[mammal]]s. Isaviruses infect salmon; thogotoviruses infect [[vertebrate]]s and [[invertebrate]]s, such as [[mosquito]]es and [[sea lice]].<ref name="ICTVdb">{{Cite web | year = 2006 | title = Index of Viruses - Orthomyxoviridae (2006). In: ICTVdB - The Universal Virus Database, version 4 | editor = Büchen-Osmond, C. | publisher = Columbia University, New York, USA | url = http://www.ncbi.nlm.nih.gov/ICTVdb/Ictv/fs_index.htm}}</ref><ref name="pmid2617637">{{cite journal |author=Jones LD, Nuttall PA |title=Non-viraemic transmission of Thogoto virus: influence of time and distance |journal=Trans. R. Soc. Trop. Med. Hyg. |volume=83 |issue=5 |pages=712–4 |year=1989 |pmid=2617637|doi=10.1016/0035-9203(89)90405-7}}</ref><ref>{{cite web | url = http://www.nimr.mrc.ac.uk/MillHillEssays/1999/isa.htm | title = Infectious Salmon Anaemia | accessdate = 2007-09-14 | author = Barry Ely | date = 1999 | work = Mill Hill Essays | publisher = [[National Institute for Medical Research]]}}</ref><ref name="pmid11678233">{{cite journal | author = Raynard RS, Murray AG, Gregory A | title = Infectious salmon anaemia virus in wild fish from Scotland | journal = Dis. Aquat. Org. | volume = 46 | issue = 2 | pages = 93–100 | year = 2001 | pmid = 11678233| doi = 10.3354/dao046093}}</ref>
The three genera of Influenzavirus, which are identified by antigenic differences in their [[nucleoprotein]] and [[matrix protein]] infect vertebrates as follows:<ref name="ICTVdb"/>
* [[Influenzavirus A]] cause of all [[flu pandemic]]s and infect [[human]]s, other [[mammal]]s and [[bird]]s,
* [[Influenzavirus B]] infect [[human]]s and [[pinniped|seal]]s, and
* [[Influenzavirus C]] infect [[human]]s and [[pig]]s.
==Morphology==
[[Image:3D Influenza virus.png|thumb|200px|right|Structure of the influenza virion. The [[hemagglutinin]] (HA) and [[neuraminidase]] (NA) proteins are shown on the surface of the particle. The viral RNAs that make up the genome are shown as red coils inside the particle and bound to Ribonuclear Proteins (RNPs).]]
The [[virion]]s have envelopes and occur in pleomorphic and filamentous forms. In general the virus's morphology is spherical with particles 50 to 120 [[nanometer|nm]] in diameter, or filamentous virions 20 nm in diameter and 200 to 300 (-3000) nm long. There are some 500 distinct spike-like surface projections of the envelope each projecting 10 to 14 nm from the surface with some types (i.e. [[hemagglutinin esterase]] (HEF)) densely dispersed over the surface, and with others (i.e. [[hemagglutinin]] (HA)) spaced widely apart.
The major [[glycoprotein]] (HA) is interposed irregularly by clusters of [[neuraminidase]] (NA), with a ratio of HA to NA of about 4-5 to 1.
[[Lipoprotein]] membranes enclose the nucleo[[capsid]]s; nucleoproteins of different size classes with a loop at each end; the arrangement within the virion is uncertain. The nucleocapsids are filamentous and fall in the range of 50 to 130 nm long and 9 to 15 nm in diameter. They have a helical symmetry.
==Nucleic Acid==
Viruses of this family contain 7 to 8 segments of linear [[Sense (molecular biology)|negative-sense]] single stranded RNA.
The total genome length is 12000-15000 [[nucleotide]]s (nt). The largest segment 2300-2500 nt; of second largest 2300-2500 nt; of third 2200-2300 nt; of fourth 1700-1800 nt; of fifth 1500-1600 nt; of sixth 1400-1500 nt; of seventh 1000-1100 nt; of eighth 800-900 nt. Genome sequence has terminal repeated sequences; repeated at both ends. Terminal repeats at the 5'-end 12-13 nucleotides long. Nucleotide sequences of 3'-terminus identical; the same in genera of same family; most on RNA (segments), or on all RNA species. Terminal repeats at the 3'-end 9-11 nucleotides long. Encapsidated nucleic acid is solely genomic. Each virion may contain defective interfering copies.
==Classification and nomenclature==
In a [[phylogenetic]]-based [[taxonomy]] the "[[RNA virus]]es" includes the "[[Sense (molecular biology)|negative-sense ssRNA viruses]]" which includes the Order "''[[Mononegavirales]]''", and the Family "''Orthomyxoviridae''" (among others). The species and serotypes of ''Orthomyxoviridae'' are shown in the following table.
{| border="1" cellpadding="4"
|+ <br>'''Orthomyxoviridae Genera, Species, And Serotypes'''<br>
|- valign="BOTTOM"
| width="20%" | '''''[[Genus]]'''''
| width="30%" | '''''[[Species]]''''' (* indicates [[type species]])
| width="30%" | '''''[[Serovar|Serotypes]]''''' or '''''Subtypes'''''
| width="20%" | '''''[[Host (biology)|Hosts]]'''''
|- valign="TOP"
| [[Influenzavirus A]]
| [[Influenza A virus]] (*)
| [[H1N1]], [[H1N2]], [[H2N2]], [[H3N1]], [[H3N2]], [[H3N8]], [[H5N1]], [[H5N2]], [[H5N3]], [[H5N8]], [[H5N9]], [[H7N1]], [[H7N2]], [[H7N3]], [[H7N4]], [[H7N7]], [[H9N2]], [[H10N7]]
| [[Human]], [[pig]], [[bird]], [[horse]]
|- valign="TOP"
| [[Influenzavirus B]]
| [[Influenza B virus]] (*)
| <br />
| Human, [[Earless seal|seal]]
|- valign="TOP"
| [[Influenzavirus C]]
| [[Influenza C virus]] (*)
| <br />
| Human, pig
|- valign="TOP"
| [[Isavirus]]
| [[Infectious salmon anemia]] virus (*)
| <br />
| [[Atlantic salmon]]
|-
| rowspan="2" | [[Thogotovirus]]
| valign="TOP" | [[Thogoto virus]] (*)
| valign="TOP" | <br />
| rowspan="2" | [[Tick]], [[mosquito]], [[mammal]] (including human)
|- valign="TOP"
| [[Dhori virus]]
| [[Batken virus]] <br />[[Dhori virus]]
|}
==Types of influenza virus==
There are three genera of influenza virus: [[Influenzavirus A]], [[Influenzavirus B]] and [[Influenzavirus C]]. Each genus includes only one species, or type: Influenza A virus, Influenza B virus, and Influenza C virus, respectively. Influenza A and C infect multiple species, while influenza B almost exclusively infects humans.<ref name=hay>{{cite journal | author = Hay A, Gregory V, Douglas A, Lin Y | title = The evolution of human influenza viruses | journal = Philos Trans R Soc Lond B Biol Sci | volume = 356 | issue = 1416 | pages = 1861–70 | year = 2001 | month=Dec 29 | pmid = 11779385 | url=http://www.journals.royalsoc.ac.uk/media/hf0bujxwvrcxd7nwdrwq/contributions/l/x/y/v/lxyv2p8w45geev90.pdf | format=PDF | doi = 10.1098/rstb.2001.0999}}</ref><ref>{{cite web | url = http://www.cdc.gov/flu/avian/ | title = Avian Influenza (Bird Flu) | accessdate = 2007-09-15 | publisher = Centers for Disease Control and Prevention }}</ref>
===Influenza A===
{{main|Influenzavirus A}}
Influenza A viruses are further classified, based on the viral surface proteins [[hemagglutinin]] (HA or H) and [[neuraminidase]] (NA or N). Sixteen H subtypes (or serotypes) and nine N subtypes of influenza A virus have been identified.
[[Image:InfluenzaNomenclatureDiagram.svg|thumb|300px|right|Diagram of influenza nomenclature.]]
Further variation exists; thus, specific influenza strain isolates are identified by a standard nomenclature specifying virus type, geographical location where first isolated, sequential number of isolation, year of isolation, and HA and NA subtype.<ref>{{cite book | editor = Atkinson W, Hamborsky J, McIntyre L, Wolfe S | title = Epidemiology and Prevention of Vaccine-Preventable Diseases | url = http://www.cdc.gov/vaccines/pubs/pinkbook/pink-chapters.htm | edition = 10th ed. | year = 2007 | publisher = Centers for Disease Control and Prevention | location = Washington DC}}</ref><ref>{{cite web | url = http://www.cidrap.umn.edu/cidrap/content/influenza/avianflu/biofacts/avflu_human.html | title = Avian Influenza (Bird Flu): Implications for Human Disease | accessdate = 2007-09-14 | date = [[2007-06-27]] | publisher = Center for Infectious Disease Research & Policy, [[University of Minnesota]]}}</ref>
Examples of the nomenclature are:
#A/Moscow/10/99 (H3N2)
#B/Hong Kong/330/2001
The type A viruses are the most virulent human pathogens among the three influenza types and causes the most severe disease. The serotypes that have been confirmed in [[humans]], ordered by the number of known human pandemic deaths, are:
*[[H1N1]] caused "[[Spanish Flu]]".
*[[H2N2]] caused "Asian Flu".
*[[H3N2]] caused "Hong Kong Flu".
*[[H5N1]] is a [[pandemic]] threat in 2006-7 flu season.
*[[H7N7]] has unusual zoonotic potential.<ref>{{cite journal | author = Fouchier R, Schneeberger P, Rozendaal F, Broekman J, Kemink S, Munster V, Kuiken T, Rimmelzwaan G, Schutten M, Van Doornum G, Koch G, Bosman A, Koopmans M, Osterhaus A | title = Avian influenza A virus (H7N7) associated with human conjunctivitis and a fatal case of acute respiratory distress syndrome | journal = Proc Natl Acad Sci U S A | volume = 101 | issue = 5 | pages = 1356–61 | year = 2004 | pmid = 14745020 | doi = 10.1073/pnas.0308352100}}</ref>
*[[H1N2]] is endemic in humans and pigs.
*[[H9N2]], [[H7N2]], [[H7N3]], [[H10N7]].
{| class="wikitable" style="text-align:center"
|+ Latest [[flu pandemic]]s <ref name=Hilleman>{{cite journal | author = Hilleman M | title = Realities and enigmas of human viral influenza: pathogenesis, epidemiology and control | journal = Vaccine | volume = 20 | issue = 25-26 | pages = 3068–87 | year = 2002 | month=Aug 19 | pmid = 12163258 | doi = 10.1016/S0264-410X(02)00254-2}}</ref>
! Name of pandemic !! Date !! Deaths !! Subtype involved
|-
! Asiatic (Russian) Flu
| 1889-90 || 1 million || possibly [[H2N2]]
|-
! [[Spanish flu|Spanish Flu]]
| 1918-20 || 40 million || [[H1N1]]
|-
! [[Asian Flu]]
| 1957-58 || 1 to 1.5 million || [[H2N2]]
|-
! [[Hong Kong Flu]]
| 1968-69 || 0.75 to 1 million || [[H3N2]]
|-
|}
===Influenza B===
{{main|Influenzavirus B}}
Influenza B virus is almost exclusively a human pathogen, and is less common than influenza A. The only other animal known to be susceptible to influenza B infection is the seal.<ref>{{cite journal | author = Osterhaus A, Rimmelzwaan G, Martina B, Bestebroer T, Fouchier R | title = Influenza B virus in seals | journal = Science | volume = 288 | issue = 5468 | pages = 1051–3 | year = 2000 | pmid = 10807575 | doi = 10.1126/science.288.5468.1051}}</ref> This type of influenza mutates at a rate 2-3 times lower than type A<ref>{{cite journal | author = Nobusawa E, Sato K | title = Comparison of the mutation rates of human influenza A and B viruses | journal = J Virol | volume = 80 | issue = 7 | pages = 3675–8 | year = 2006 | month=Apr | pmid = 16537638 | doi = 10.1128/JVI.80.7.3675-3678.2006}}</ref> and consequently is less genetically diverse, with only one influenza B serotype.<ref name=hay/> As a result of this lack of [[antigen]]ic diversity, a degree of immunity to influenza B is usually acquired at an early age. However, influenza B mutates enough that lasting immunity is not possible.<ref name=webster>{{cite journal | author = Webster R, Bean W, Gorman O, Chambers T, Kawaoka Y | title = Evolution and ecology of influenza A viruses | url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=1579108 |journal = Microbiol Rev | volume = 56 | issue = 1 | pages = 152–79 | year = 1992 | pmid = 1579108}}</ref> This reduced rate of antigenic change, combined with its limited host range (inhibiting cross species [[antigenic shift]]), ensures that pandemics of influenza B do not occur.<ref name=Zambon>{{cite journal | author = Zambon M | title = Epidemiology and pathogenesis of influenza | journal = J Antimicrob Chemother | volume = 44 Suppl B | issue = | pages = 3–9 | year = 1999 | month=Nov | pmid = 10877456 | url=http://jac.oxfordjournals.org/cgi/reprint/44/suppl_2/3 | doi = 10.1093/jac/44.suppl_2.3}}</ref>
===Influenza C===
{{main|Influenzavirus C}}
The influenza C virus infects [[human]]s and [[pig]]s, and can cause severe illness and local [[epidemic]]s.<ref>{{cite journal | author = Matsuzaki Y, Sugawara K, Mizuta K, Tsuchiya E, Muraki Y, Hongo S, Suzuki H, Nakamura K | title = Antigenic and genetic characterization of influenza C viruses which caused two outbreaks in Yamagata City, Japan, in 1996 and 1998 | url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=11825952 | journal = J Clin Microbiol | volume = 40 | issue = 2 | pages = 422–9 | year = 2002 | pmid = 11825952 | doi = 10.1128/JCM.40.2.422-429.2002}}</ref> However, influenza C is less common than the other types and usually seems to cause mild disease in children.<ref>{{cite journal | author = Matsuzaki Y, Katsushima N, Nagai Y, Shoji M, Itagaki T, Sakamoto M, Kitaoka S, Mizuta K, Nishimura H | title = Clinical features of influenza C virus infection in children | journal = J Infect Dis | volume = 193 | issue = 9 | pages = 1229–35 | year = 2006 | month=May 1 | pmid = 16586359 | doi = 10.1086/502973}}</ref><ref>{{cite journal | author = Katagiri S, Ohizumi A, Homma M | title = An outbreak of type C influenza in a children's home | journal = J Infect Dis | volume = 148 | issue = 1 | pages = 51–6 | year = 1983 | month=Jul | pmid = 6309999}}</ref>
==Structure and properties==
:''An in-depth example can be found at [[H5N1 genetic structure]]''
The following applies for [[Influenzavirus A|Influenza A]] viruses, although other influenza strains are very similar in structure<ref> International Committee on Taxonomy of Viruses descriptions of: [http://www.ncbi.nlm.nih.gov/ICTVdb/ICTVdB/46000000.htm Orthomyxoviridae] [http://www.ncbi.nlm.nih.gov/ICTVdb/ICTVdB/46040000.htm Influenzavirus B] [http://www.ncbi.nlm.nih.gov/ICTVdb/ICTVdB/00.046.0.02.htm Influenzavirus C]</ref>:
The influenza A virus particle or ''virion'' is 80-120 nm in diameter and usually roughly spherical, although filamentous forms can occur.<ref>{{cite web |author=International Committee on Taxonomy of Viruses |title=The Universal Virus Database, version 4: Influenza A |url=http://www.ncbi.nlm.nih.gov/ICTVdb/ICTVdB/00.046.0.01.htm}}</ref> Unusually for a virus, the influenza A [[genome]] is not a single piece of nucleic acid; instead, it contains eight pieces of segmented negative-sense [[RNA]] (13.5 kilobases total), which encode 11 proteins (HA, NA, NP, M1, M2, NS1, NEP, PA, PB1, PB1-F2, PB2).<ref name=Ghedin>{{cite journal | author = Ghedin E, Sengamalay N, Shumway M, Zaborsky J, Feldblyum T, Subbu V, Spiro D, Sitz J, Koo H, Bolotov P, Dernovoy D, Tatusova T, Bao Y, St George K, Taylor J, Lipman D, Fraser C, Taubenberger J, Salzberg S | title = Large-scale sequencing of human influenza reveals the dynamic nature of viral genome evolution | journal = Nature | volume = 437 | issue = 7062 | pages = 1162–6 | year = 2005 | month=Oct 20 | pmid = 16208317 | doi = 10.1038/nature04239}}</ref> The best-characterised of these viral proteins are [[hemagglutinin]] and [[neuraminidase]], two large [[glycoprotein]]s found on the outside of the viral particles. Neuraminidase is an [[enzyme]] involved in the release of progeny virus from infected cells, by cleaving sugars that bind the mature viral particles. By contrast, hemagglutinin is a [[lectin]] that mediates binding of the virus to target cells and entry of the viral genome into the target cell.<ref>{{cite journal | author = Suzuki Y | title = Sialobiology of influenza: molecular mechanism of host range variation of influenza viruses | url=http://www.jstage.jst.go.jp/article/bpb/28/3/399/_pdf | journal = Biol Pharm Bull | volume = 28 | issue = 3 | pages = 399–408 | year = 2005 | pmid = 15744059 | doi = 10.1248/bpb.28.399}}</ref> The hemagglutinin (H) and neuraminidase (N) [[protein]]s are targets for antiviral drugs.<ref>{{cite journal | author = Wilson J, von Itzstein M | title = Recent strategies in the search for new anti-influenza therapies | journal = Curr Drug Targets | volume = 4 | issue = 5 | pages = 389–408 | year = 2003 | month=Jul | pmid = 12816348 | doi = 10.2174/1389450033491019}}</ref> These proteins are also recognised by [[antibody|antibodies]], i.e. they are [[antigen]]s.<ref name=Hilleman/> The responses of antibodies to these proteins are used to classify the different [[serotype]]s of influenza A viruses, hence the ''H'' and ''N'' in ''H5N1''.
==Infection and replication==
[[Image:Virus Replication.svg|thumb|400px|right|Invasion and replication of the influenza virus. The steps in this process are discussed in the text.]]
Typically, influenza is transmitted from infected mammals through the air by coughs or sneezes, creating [[particulate|aerosols]] containing the virus, and from infected birds through their [[feces| droppings]]. Influenza can also be transmitted by [[saliva]], [[mucus|nasal secretions]], [[feces]] and [[blood]]. Infections occur through contact with these bodily fluids or with contaminated surfaces. Flu viruses can remain infectious for about one week at human body temperature, over 30 days at 0 [[Celsius|°C]] (32 [[Fahrenheit|°F]]), and indefinitely at very low temperatures (such as lakes in northeast [[Siberia]]). They can be inactivated easily by [[disinfectant]]s and [[detergent]]s.<ref>{{cite journal | last = Suarez | first = D | coauthors = Spackman E, Senne D, Bulaga L, Welsch A, Froberg K | title = The effect of various disinfectants on detection of avian influenza virus by real time RT-PCR | journal = Avian Dis | volume = 47 | issue = 3 Suppl | pages = 1091–5 | year = 2003 | pmid = 14575118}}</ref><ref>[http://www.cidrap.umn.edu/cidrap/content/influenza/avianflu/biofacts/avflu_human.html Avian Influenza (Bird Flu)]: Implications for Human Disease. Physical characteristics of influenza A viruses. UMN CIDRAP.</ref><ref name = "NHZ2006-11-30">[http://www.nzherald.co.nz/category/story.cfm?c_id=204&objectid=10413124 Flu viruses 'can live for decades' on ice], NZ Herald, November 30, 2006.</ref>
The viruses bind to a cell through interactions between its [[hemagglutinin]] glycoprotein and [[sialic acid]] sugars on the surfaces of [[epithelium|epithelial cells]] in the lung and throat (Stage 1 in infection figure).<ref name=Wagner>{{cite journal | author = Wagner R, Matrosovich M, Klenk H | title = Functional balance between haemagglutinin and neuraminidase in influenza virus infections | journal = Rev Med Virol | volume = 12 | issue = 3 | pages = 159–66 | year = 2002 | month=May-Jun| pmid = 11987141 | doi = 10.1002/rmv.352}}</ref> The cell imports the virus by [[endocytosis]]. In the acidic [[endosome]], part of the haemagglutinin protein fuses the viral envelope with the vacuole's membrane, releasing the viral RNA (vRNA) molecules, accessory proteins and [[RNA replicase|RNA-dependent RNA polymerase]] into the [[cytoplasm]] (Stage 2).<ref>{{cite journal | author = Lakadamyali M, Rust M, Babcock H, Zhuang X | title = Visualizing infection of individual influenza viruses | journal = Proc Natl Acad Sci U S A | volume = 100 | issue = 16 | pages = 9280–5 | year = 2003 | month=Aug 5 | pmid = 12883000 | doi = 10.1073/pnas.0832269100}}</ref> These proteins and vRNA form a complex that is transported into the [[cell nucleus]], where the RNA-dependent RNA transcriptase begins transcribing complementary positive-sense vRNA (Steps 3a and b).<ref>{{cite journal | author = Cros J, Palese P | title = Trafficking of viral genomic RNA into and out of the nucleus: influenza, Thogoto and Borna disease viruses | journal = Virus Res | volume = 95 | issue = 1-2 | pages = 3–12 | year = 2003 | month=Sep | pmid = 12921991 | doi = 10.1016/S0168-1702(03)00159-X}}</ref> The vRNA is either exported into the cytoplasm and translated (step 4), or remains in the nucleus. Newly-synthesised viral proteins are either secreted through the [[Golgi apparatus]] onto the cell surface (in the case of neuraminidase and hemagglutinin, step 5b) or transported back into the nucleus to bind vRNA and form new viral genome particles (step 5a). Other viral proteins have multiple actions in the host cell, including degrading cellular [[mRNA]] and using the released [[nucleotide]]s for vRNA synthesis and also inhibiting [[translation]] of host-cell mRNAs.<ref>{{cite journal | author = Kash J, Goodman A, Korth M, Katze M | title = Hijacking of the host-cell response and translational control during influenza virus infection | journal = Virus Res | volume = 119 | issue = 1 | pages = 111–20 | year = 2006 | month=Jul | pmid = 16630668 | doi = 10.1016/j.virusres.2005.10.013}}</ref>
Negative-sense vRNAs that form the [[genome]]s of future viruses, RNA-dependent RNA transcriptase, and other viral proteins are assembled into a virion. Hemagglutinin and neuraminidase molecules cluster into a bulge in the cell membrane. The vRNA and viral core proteins leave the nucleus and enter this membrane protrusion (step 6). The mature virus buds off from the cell in a sphere of host phospholipid membrane, acquiring hemagglutinin and neuraminidase with this membrane coat (step 7).<ref>{{cite journal | author = Nayak D, Hui E, Barman S | title = Assembly and budding of influenza virus | journal = Virus Res | volume = 106 | issue = 2 | pages = 147–65 | year = 2004 | month=Dec | pmid = 15567494 | doi = 10.1016/j.virusres.2004.08.012}}</ref> As before, the viruses adhere to the cell through hemagglutinin; the mature viruses detach once their [[neuraminidase]] has cleaved sialic acid residues from the host cell.<ref name=Wagner/> After the release of new influenza virus, the host cell dies.
Because of the absence of RNA [[proofread]]ing enzymes, the RNA-dependent RNA transcriptase makes a single nucleotide insertion error roughly every 10 thousand nucleotides, which is the approximate length of the influenza vRNA. Hence, nearly every newly-manufactured influenza virus will contain mutation in its genome.<ref>{{cite journal | author = Drake J | title = Rates of spontaneous mutation among RNA viruses | journal = Proc Natl Acad Sci U S A | volume = 90 | issue = 9 | pages = 4171–5 | year = 1993 | month=May 1 | pmid = 8387212 | doi = 10.1073/pnas.90.9.4171}}</ref> The separation of the genome into eight separate segments of vRNA allows mixing or ''reassortment'' of the genes if more than one variety of influenza virus has infected the same cell. The resulting alteration in the genome segments packaged in to viral progeny confers new behavior, sometimes the ability to infect new host species or to overcome protective immunity of host populations to its old genome (in which case it is called an [[antigenic shift]]).<ref name=Hilleman/>
==See also==
{{Viruses}}
{{Influenza}}
==Sources==
{{reflist|2}}
[[Category:Orthomyxoviridae| ]]
[[Category:Virology]]
[[Category:Viruses]]
[[Category:Microbiology]]
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