View source for H5N1 genetic structure

{{Short description|Genetic structure of Influenza A virus}}
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{{H5N1}}
The '''genetic structure of H5N1''', a highly pathogenic avian influenza virus ([[influenza A virus subtype H5N1]]), is characterized by a segmented RNA genome consisting of eight gene segments that encode for various viral proteins essential for replication, host adaptation, and immune evasion.

== Virus ==
{{Main|Influenza A virus subtype H5N1}}

Influenza A virus subtype H5N1 (A/H5N1) is a subtype of the [[influenza A virus]], which causes [[influenza]] (flu), predominantly in birds. It is [[enzootic]] (maintained in the population) in many bird populations, and also [[panzootic]] (affecting animals of many species over a wide area).<ref>{{Cite web |date=3 October 2023 |title=Influenza (Avian and other zoonotic) |url=https://www.who.int/news-room/fact-sheets/detail/influenza-(avian-and-other-zoonotic) |access-date=2024-05-06 |website=who.int |publisher=[[World Health Organization]] |language=en}}</ref> A/H5N1 virus can also infect mammals (including humans) that have been exposed to infected birds; in these cases, symptoms are frequently severe or fatal. All subtypes of the influenza A virus share the same genetic structure and are potentially able to exchange genetic material by means of [[reassortment]]<ref name="Bourk_2024">{{Cite web | vauthors = Bourk I |date=26 April 2024 |title='Unprecedented': How bird flu became an animal pandemic |url=https://www.bbc.com/future/article/20240425-how-dangerous-is-bird-flu-spread-to-wildlife-and-humans |access-date=2024-05-08 |website=bbc.com |publisher=[[BBC]] |language=en-GB}}</ref><ref>{{cite journal | vauthors = Shao W, Li X, Goraya MU, Wang S, Chen JL | title = Evolution of Influenza A Virus by Mutation and Re-Assortment | journal = International Journal of Molecular Sciences | volume = 18 | issue = 8 | pages = 1650 | date = August 2017 | pmid = 28783091 | pmc = 5578040 | doi = 10.3390/ijms18081650 | doi-access = free }}</ref>

<!--Transmission-->
A/H5N1 virus is shed in the saliva, mucus, and feces of infected birds; other infected animals may shed bird flu viruses in respiratory secretions and other body fluids (such as milk).<ref name="cdc.gov_2024">{{Cite web |date=2024-04-19 |title=Prevention and Antiviral Treatment of Bird Flu Viruses in People {{!}} Avian Influenza (Flu) |url=https://www.cdc.gov/flu/avianflu/prevention.htm |access-date=2024-05-08 |website=cdc.gov |publisher=[[Centers for Disease Control]] |language=en-us |location=US}}</ref> The virus can spread rapidly through poultry flocks and among wild birds.<ref name="cdc.gov_2024" /> An estimated half a billion farmed birds have been slaughtered in efforts to contain the virus.<ref name="Bourk_2024" />

<!--Symptoms and prognosis - chickens-->
Symptoms of A/H5N1 influenza vary according to both the strain of virus underlying the infection and on the species of bird or mammal affected.<ref>{{Cite web |title=Bird flu (avian influenza) |url=http://www.betterhealth.vic.gov.au/health/conditionsandtreatments/bird-flu-avian-influenza |access-date=2024-05-09 |website=betterhealth.vic.gov.au |publisher=Department of Health & Human Services |language=en |location=Victoria, Australia}}</ref><ref name="gov.uk_2021">{{Cite web |date=2021-11-18 |title=Avian influenza: guidance, data and analysis |url=https://www.gov.uk/government/collections/avian-influenza-guidance-data-and-analysis |access-date=2024-05-09 |website=gov.uk |language=en-gb}}</ref> Classification as either Low Pathogenic Avian Influenza (LPAI) or High Pathogenic Avian Influenza (HPAI) is based on the severity of symptoms in domestic [[Chicken|chickens]] and does not predict the severity of symptoms in other species.<ref name="cdc.gov_2022">{{Cite web |date=2022-06-14 |title=Avian Influenza in Birds |url=https://www.cdc.gov/flu/avianflu/avian-in-birds.htm |access-date=2024-05-06 |website=cdc.gov |publisher=Centers for Disease Control and Prevention |language=en-us |location=US}}</ref> Chickens infected with LPAI A/H5N1 virus display mild symptoms or are [[asymptomatic]], whereas HPAI A/H5N1 causes serious breathing difficulties, a significant drop in egg production, and sudden death.<ref>{{Cite web |date=2022-12-13 |title=Bird flu (avian influenza): how to spot and report it in poultry or other captive birds |url=https://www.gov.uk/guidance/avian-influenza-bird-flu |access-date=2024-05-06 |website=gov.uk |publisher=Department for Environment, Food & Rural Affairs and Animal and Plant Health Agency |language=en-gb |location=UK}}</ref>

<!--Symptoms and prognosis - humans & mammals-->
In mammals, including humans, A/H5N1 influenza (whether LPAI or HPAI) is rare. Symptoms of infection vary from mild to severe, including fever, diarrhoea, and cough.<ref name="gov.uk_2021" /> Human infections with A/H5N1 virus have been reported in 23 countries since 1997, resulting in severe pneumonia and death in about 50% of cases.<ref>{{Cite web |date=2024-02-01 |title=Influenza Type A Viruses |url=https://www.cdc.gov/flu/avianflu/influenza-a-virus-subtypes.htm |access-date=2024-05-03 |website=cdc.gov |publisher=Centers for Disease Control and Prevention |language=en-us |location=US}}</ref> {{#section:Human mortality from H5N1|H5N1_WHO}}

<!--Epidemiology-->
A/H5N1 influenza virus was first identified in farmed birds in southern China in 1996.<ref>{{Cite web |date=2023-06-06 |title=Emergence and Evolution of H5N1 Bird Flu {{!}} Avian Influenza (Flu) |url=https://www.cdc.gov/flu/avianflu/communication-resources/bird-flu-origin-infographic.html |access-date=2024-05-03 |website=cdc.gov |publisher=Centers for Disease Control and Prevention |language=en-us |location=US}}</ref> Between 1996 and 2018, A/H5N1 coexisted in bird populations with other subtypes of the virus, but since then, the highly pathogenic subtype HPAI A(H5N1) has become the dominant strain in bird populations worldwide.<ref>{{cite journal | vauthors = Huang P, Sun L, Li J, Wu Q, Rezaei N, Jiang S, Pan C | title = Potential cross-species transmission of highly pathogenic avian influenza H5 subtype (HPAI H5) viruses to humans calls for the development of H5-specific and universal influenza vaccines | journal = Cell Discovery | volume = 9 | issue = 1 | pages = 58 | date = June 2023 | pmid = 37328456 | pmc = 10275984 | doi = 10.1038/s41421-023-00571-x }}</ref> Some strains of A/H5N1 which are highly pathogenic to chickens have adapted to cause mild symptoms in ducks and geese,<ref>{{Cite web |date=2024-04-22 |title=Highlights in the History of Avian Influenza (Bird Flu) Timeline – 2020-2024 {{!}} Avian Influenza (Flu) |url=https://www.cdc.gov/flu/avianflu/timeline/avian-timeline-2020s.htm |access-date=2024-05-08 |website=cdc.gov |publisher=Centers for Disease Control and Prevention |language=en-us |location=US}}</ref><ref name="cdc.gov_2022" /> and are able to spread rapidly through bird migration.<ref>{{cite journal | vauthors = Caliendo V, Lewis NS, Pohlmann A, Baillie SR, Banyard AC, Beer M, Brown IH, Fouchier RA, Hansen RD, Lameris TK, Lang AS, Laurendeau S, Lung O, Robertson G, van der Jeugd H, Alkie TN, Thorup K, van Toor ML, Waldenström J, Yason C, Kuiken T, Berhane Y | title = Transatlantic spread of highly pathogenic avian influenza H5N1 by wild birds from Europe to North America in 2021 | journal = Scientific Reports | volume = 12 | issue = 1 | pages = 11729 | date = July 2022 | pmid = 35821511 | pmc = 9276711 | doi = 10.1038/s41598-022-13447-z | bibcode = 2022NatSR..1211729C }}</ref> Mammal species that have been recorded with H5N1 infection include cows, seals, goats, and skunks.<ref>{{Cite web |date=2024-05-02 |title=Bird flu is bad for poultry and cattle. Why it's not a dire threat for most of us — yet |url=https://www.nbcnews.com/health/health-news/bird-flu-bad-poultry-cattle-know-threat-people-rcna150494 |access-date=2024-05-09 |website= |publisher=NBC News |language=en}}</ref>

<!--Pandemic potential and prevention-->
Due to the high lethality and [[virulence]] of HPAI A(H5N1), its worldwide presence, its increasingly diverse [[Host (biology)|host]] [[Natural reservoir|reservoir]], and its significant ongoing mutations, the H5N1 virus is regarded as the world's largest [[pandemic]] threat.<ref>{{Cite news | vauthors = McKie R |date=2024-04-20 |title=Next pandemic likely to be caused by flu virus, scientists warn |url=https://www.theguardian.com/world/2024/apr/20/next-pandemic-likely-to-be-caused-by-flu-virus-scientists-warn |access-date=2024-05-09 |work=The Observer |language=en-GB |issn=0029-7712}}</ref> Domestic poultry may potentially be protected from specific strains of the virus by vaccination.<ref>{{Cite web |date=2023-10-10 |title=Vaccination of poultry against highly pathogenic avian influenza – Available vaccines and vaccination strategies |url=https://www.efsa.europa.eu/en/news/vaccination-poultry-against-highly-pathogenic-avian-influenza-available-vaccines-and |access-date=2024-05-09 |website=efsa.europa.eu |publisher= |language=en}}</ref> In the event of a serious outbreak of H5N1 flu among humans, health agencies have prepared "candidate" vaccines that may be used to prevent infection and control the outbreak; however, it could take several months to ramp up mass production.<ref name="cdc.gov_2024" /><ref>{{Cite web |date=2024-05-01 |title=Two possible bird flu vaccines could be available within weeks, if needed |url=https://www.nbcnews.com/health/health-news/two-possible-bird-flu-vaccines-available-weeks-needed-rcna149961 |access-date=2024-05-09 |website= |publisher=NBC News |language=en}}</ref><ref>{{Cite web |title=Avian influenza (bird flu) {{!}} European Medicines Agency |url=https://www.ema.europa.eu/en/human-regulatory-overview/public-health-threats/avian-influenza-bird-flu |access-date=2024-05-09 |website=ema.europa.eu}}</ref>

== Nomenclature ==
{{Excerpt|Influenza A virus|Influenza virus nomenclature}}
{{Excerpt|Avian influenza|Highly pathogenic avian influenza}}

==Structure and genome==
[[File:Viruses-10-00497-g001.png|thumb|Influenza A virus structure]]

=== Structure ===
The influenza A virus has a [[Sense (molecular biology)|negative-sense]], single-stranded, segmented [[RNA virus|RNA genome]], enclosed in a lipid envelope. The virus particle (also called the '''virion''') is 80–120 nanometers in diameter such that the smallest virions adopt an elliptical shape; larger virions have a filamentous shape.<ref>{{cite journal | vauthors = Dadonaite B, Vijayakrishnan S, Fodor E, Bhella D, Hutchinson EC | title = Filamentous influenza viruses | journal = The Journal of General Virology | volume = 97 | issue = 8 | pages = 1755–1764 | date = August 2016 | pmid = 27365089 | pmc = 5935222 | doi = 10.1099/jgv.0.000535 }}</ref>

Core - The central core of the virion contains the viral RNA genome, which is made of eight separate segments.<ref name="Bouvier_2008">{{cite journal | vauthors = Bouvier NM, Palese P | title = The biology of influenza viruses | journal = Vaccine | volume = 26 | issue = Suppl 4 | pages = D49–D53 | date = September 2008 | pmid = 19230160 | pmc = 3074182 | doi = 10.1016/j.vaccine.2008.07.039 }}</ref> The nucleoprotein (NP) coats  the viral RNA to form a ribonucleoprotein that assumes a helical (spiral) configuration. Three large proteins (PB<sub>1</sub>, PB<sub>2</sub>, and PA), which are responsible for RNA transcription and replication, are bound to each segment of viral RNP.<ref name="Bouvier_2008" /><ref name="Shaffer_2018">{{Cite web | vauthors = Shaffer C |date=2018-03-07 |title=Influenza A Structure |url=https://www.news-medical.net/life-sciences/Influenza-A-Structure.aspx |access-date=2024-06-18 |website=News-Medical |language=en}}</ref><ref name="World Health Organization_2010">{{Cite web |date=13 May 2010 |title=Virology of human influenza |url=https://www.who.int/europe/news-room/fact-sheets/item/virology-of-human-influenza |access-date=2024-06-19 |website=World Health Organization |language=en}}</ref>

Capsid - The matrix protein M1 forms a layer between the nucleoprotein and the envelope, called the [[capsid]].<ref name="Bouvier_2008" /><ref name="Shaffer_2018" /><ref name="World Health Organization_2010" />

Envelope - The [[viral envelope]] consists of a lipid bilayer derived from the host cell. Two viral proteins; hemagglutinin (HA) and neuraminidase (NA), are inserted into the envelope and are exposed as spikes on the surface of the virion. Both proteins are [[Antigen|antigenic]]; a host's immune system can react to them and produce antibodies in response. The M2 protein forms an ion channel in the envelope and is responsible for uncoating the virion once it has bound to a host cell.<ref name="Bouvier_2008" /><ref name="Shaffer_2018" /><ref name="World Health Organization_2010" />

=== Genome ===
The table below presents a concise summary of the influenza genome and the principal functions of the proteins which are encoded. Segments are conventionally numbered from 1 to 8 in descending order of length.<ref name="krammer">{{cite journal | vauthors = Krammer F, Smith GJ, Fouchier RA, Peiris M, Kedzierska K, Doherty PC, Palese P, Shaw ML, Treanor J, Webster RG, García-Sastre A | title = Influenza | journal = Nature Reviews. Disease Primers | volume = 4 | issue = 1 | pages = 3 | date = June 2018 | pmid = 29955068 | pmc = 7097467 | doi = 10.1038/s41572-018-0002-y }}</ref><ref name="Jakob et al">{{cite journal | vauthors = Jakob C, Paul-Stansilaus R, Schwemmle M, Marquet R, Bolte H | title = The influenza A virus genome packaging network - complex, flexible and yet unsolved | journal = Nucleic Acids Research | volume = 50 | issue = 16 | pages = 9023–9038 | date = September 2022 | pmid = 35993811 | doi = 10.1093/nar/gkac688 | pmc = 9458418 }}</ref><ref name="Dou et al">{{cite journal | vauthors = Dou D, Revol R, Östbye H, Wang H, Daniels R | title = Influenza A Virus Cell Entry, Replication, Virion Assembly and Movement | journal = Frontiers in Immunology | volume = 9 | pages = 1581 | date = 2018-07-20 | pmid = 30079062 | pmc = 6062596 | doi = 10.3389/fimmu.2018.01581 | doi-access = free }}</ref><ref name="Rashid et al">{{cite journal | vauthors = Rashid F, Xie Z, Li M, Xie Z, Luo S, Xie L | title = Roles and functions of IAV proteins in host immune evasion | language = English | journal = Frontiers in Immunology | volume = 14 | pages = 1323560 | date = 2023-12-13 | pmid = 38152399 | pmc = 10751371 | doi = 10.3389/fimmu.2023.1323560 | doi-access = free }}</ref>
{| class="wikitable"
|RNA Segment
|Length
|Protein
|Function
|-
|1- PB2
|2341
|PB2 (Polymerase Basic 2)
|A component of the viral RNA [[polymerase]].
PB2 also inhibits [[JAK-STAT signaling pathway|JAK1/STAT signaling]] to inhibit host innate immune response
|-
| rowspan="2" |2- PB1
| rowspan="2" |2341
|PB1 (Polymerase Basic 1)
|A component of the viral RNA polymerase.
It also degrades the host cell’s [[Mitochondrial antiviral-signaling protein|mitochondrial antiviral signaling protein]]
|-
|PB1-F2 (Polymerase Basic 1-Frame 2)
|An accessory protein of most IAVs. Not needed for virus replication and growth, it interferes with the host immune response.
|-
|3- PA
|2233
|PA (Polymerase Acid)
|A component of the viral RNA polymerase
|-
|
|
|PA-X
|Arises from a [[ribosomal frameshift]] in the PA segment. Inhibits innate host immune responses, such as [[cytokine]] and [[interferon]] production.
|-
|4- HA
|1775
|[[Hemagglutinin (influenza)|HA (Hemagglutinin)]]
|Part of the viral envelope, a protein that binds the virion to host cells, enabling the virus’s RNA genetic material to invade it
|-
|5- NP
|1565
|[[Nucleoprotein|NP (Nucleoprotein)]]
|The nucleoprotein associates with the viral RNA to form a ribonucleoprotein (RNP).
At the early stage of infection, the RNP binds to the host cell’s '''[[Importin α|importin-α]]''' which transports it into the host cell nucleus, where the viral RNA is transcribed and replicated.

At a later stage of infection, newly manufactured viral RNA segments assemble with the NP protein and polymerase (PB1, PB2 and PA) to form the core of a progeny virion
|-
|6- NA
|1409
|[[Neuraminidase|NA (Neuraminidase)]]
|Part of the viral envelope. NA enables the newly assembled virions to escape the host cell and go on to propagate the infection.
NA also facilitates the movement of infective virus particles through mucus, enabling them to reach host epithelial cells.
|-
| rowspan="2" |7- M
| rowspan="2" |1027
|[[Viral matrix protein|M1 (Matrix Protein 1)]]
|Forms the [[capsid]], which coats the viral nucleoproteins and supports the structure of the viral envelope.
M1 also assists with the function of the NEP protein.
|-
|[[M2 proton channel|M2 (Matrix Protein 2)]]
|Forms a [[Proton pump|proton channel]] in the viral envelope, which is activated once a virion has bound to a host cell. This uncoats the virus, exposing its infective contents to the cytoplasm of the host cell
|-
| rowspan="2" |8- NS
| rowspan="2" |890
|[[NS1 influenza protein|NS1 (non-structural protein 1)]]
|Counteracts the host’s natural immune response and inhibits interferon production.
|-
|NEP (Nuclear Export Protein, formerly NS2 non-structural protein 2)
|Cooperates with the M1 protein to mediate the export of viral RNA copies from nucleus into cytoplasm in the late stage of viral replication
|}
Three viral proteins - PB1, PB2, and PA - associate to form the [[RNA-dependent RNA polymerase]] (RdRp) which functions to [[Transcription (biology)|transcribe]] and [[RNA-dependent RNA polymerase|replicate]] the viral RNA.

'''Viral messenger RNA Transcription -''' The RdRp complex transcribes viral mRNAs by using a mechanism called [[Cap snatching|cap-snatching]]. It consists in the hijacking and cleavage of host [[Five-prime cap|capped]] [[Primary transcript|pre-mRNAs]]. Host cell mRNA is cleaved near the cap to yield a [[Directionality (molecular biology)#5′-end|primer]] for the transcription of positive-sense viral mRNA using the negative-sense viral RNA as a template.<ref>{{cite journal | vauthors = Decroly E, Canard B | title = Biochemical principles and inhibitors to interfere with viral capping pathways | journal = Current Opinion in Virology | volume = 24 | pages = 87–96 | date = June 2017 | pmid = 28527860 | pmc = 7185569 | doi = 10.1016/j.coviro.2017.04.003 }}</ref> The host cell then transports the viral mRNA into the cytoplasm where [[Ribosome|ribosomes]] manufacture the viral proteins.<ref name="krammer" /><ref name="Jakob et al" /><ref name="Dou et al" /><ref name="Rashid et al" />

'''Replication of the viral RNA -'''The replication of the influenza genome involves two steps. The RdRp first of all transcribes the negative-sense viral genome into a positive-sense complimentary RNA (cRNA), then the cRNAs are used as templates to transcribe new negative-sense vRNA copies. These are exported from the nucleus and assemble near the cell membrane to form the core of new virions.<ref name="krammer" /><ref name="Jakob et al" /><ref name="Dou et al" /><ref name="Rashid et al" />

==Surface encoding gene segments==
All influenza A viruses have two gene segments titled HA and NA which code for the [[antigen]]ic proteins hemagglutin and neuraminidase which are located on the external envelope of the virus.

=== HA ===
HA codes for [[Hemagglutinin (influenza)|hemagglutinin]], which is an [[antigen]]ic [[glycoprotein]] found on the surface of the [[influenza]] [[virus]]es and is responsible for binding the virus to the [[cell (biology)|cell]] that is being infected. [[Hemagglutinin]] forms spikes at the surface of flu viruses that function to attach viruses to [[Cell (biology)|cells]]. This attachment is required for efficient transfer of flu virus genes into cells, a process that can be blocked by antibodies that bind to the hemagglutinin proteins. One genetic factor in distinguishing between human flu viruses and avian flu viruses is that avian influenza HA bind to alpha 2-3 [[sialic acid]] receptors while human influenza HA bind alpha 2-6 sialic acid receptors.<ref>{{cite journal | url = http://www.cissm.umd.edu/papers/files/greninger.pdf | date = July 16, 2004 | vauthors = Greninger A | author1-link = Alexander L. Greninger | title = The Definition and Measurement of Dangerous Research | journal = CISSM Working Paper | access-date = 2006-12-09 | archive-url = https://web.archive.org/web/20061108210823/http://www.cissm.umd.edu/papers/files/greninger.pdf | archive-date = November 8, 2006 | url-status = dead }}</ref>

=== NA ===
NA codes for [[neuraminidase]] which is an [[antigen]]ic [[glycoprotein]] [[enzyme]] found on the surface of the [[influenza]] [[virus]]es. It helps the release of progeny viruses from infected cells. The antiviral drugs [[Oseltamivir|Tamiflu]] and [[Zanamivir|Relenza]]  work by inhibiting some strains of [[neuraminidase]].<ref>[http://www.scidev.net/gateways/index.cfm?fuseaction=readitem&rgwid=4&item=News&itemid=3050&language=1 Scidev.net News] {{Webarchive|url=https://web.archive.org/web/20080205161953/http://www.scidev.net/gateways/index.cfm?fuseaction=readitem&rgwid=4&item=News&itemid=3050&language=1 |date=2008-02-05 }} article ''Bird flu protein's 'pocket' could inspire better drugs'' published August 16, 2006</ref>

== Matrix encoding gene segments ==

=== M ===
M codes for the matrix proteins (M1 and M2) that, along with the two surface proteins ([[hemagglutinin]] and [[neuraminidase]]), make up the [[capsid]] (protective coat) of the virus. It encodes by using different reading frames from the same RNA segment.

* The matrix protein [[M1 protein|M1]] forms the [[capsid]], which coats the viral nucleoproteins and supports the structure of the viral envelope. M1 also assists with the function of the NEP protein.
* The [[M2 protein|M2]] protein forms a [[Proton pump|proton channel]] in the viral envelope that uncoats the virus, thereby exposing its contents (the eight RNA segments) to the cytoplasm of the host cell. The M2 [[transmembrane protein]] is an [[ion channel]] required for efficient infection.<ref>[https://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=mmed.section.3069 Influenza virus replication] in ''Medical Microbiology, 4th edition'' edited by Samuel Baron. 1996 Chapter 58. {{ISBN|0-9631172-1-1}}.</ref>

== Nucleoprotein encoding gene segments. ==

=== NP ===
NP codes for [[Influenza virus nucleoprotein|a structural]] [[protein]] which [[Encapsidation|encapsidates]] the [[negative strand]] viral [[RNA]].<ref name="PUB00006231">{{cite journal | vauthors = Steuler H, Schröder B, Bürger H, Scholtissek C | title = Sequence of the nucleoprotein gene of influenza A/parrot/Ulster/73 | journal = Virus Research | volume = 3 | issue = 1 | pages = 35–40 | date = July 1985 | pmid = 4024728 | doi = 10.1016/0168-1702(85)90039-5 }}</ref>

=== NS ===
NS codes for two nonstructural proteins ([[NS1 influenza protein|NS1]] and Nuclear Export Protein NEP - formerly called NS2). 

* NS1 counteracts the host’s natural immune response and inhibits interferon production.
* NEP  mediates the export of influenza virus ribonucleoprotein (RNP) complexes from the nucleus into the cytoplasm, where they are assembled..<ref name="structure11">{{cite journal | vauthors = Paragas J, Talon J, O'Neill RE, Anderson DK, García-Sastre A, Palese P | title = Influenza B and C virus NEP (NS2) proteins possess nuclear export activities | journal = Journal of Virology | volume = 75 | issue = 16 | pages = 7375–7383 | date = August 2001 | pmid = 11462009 | pmc = 114972 | doi = 10.1128/JVI.75.16.7375-7383.2001 }}</ref>

== Polymerase encoding gene segments ==

=== PA ===
PA codes for the PA protein which is a component of the [[RNA polymerase|viral polymerase]].

=== PB1 ===
PB1 codes for the PB1 protein and the PB1-F2 protein.
* The PB1 protein is a component of the [[RNA polymerase|viral polymerase]].
* The PB1-F2 protein is encoded by an alternative open reading frame of the PB1 RNA segment

=== PB2 ===
PB2 codes for the PB2 protein which is a component of the [[RNA polymerase|viral polymerase]].

==Mutation==
{{Excerpt|Influenza A virus|Pandemic potential}}
{{Excerpt|Influenza A virus|Surveillance}}

== See also ==
* [[Fujian flu]]
* [[Goose Guangdong virus]]
* [[Orthomyxoviridae]]
* [[PB2 E627K mutation]]

== References ==
{{Reflist}}

== Further reading ==
{{refbegin|30em}}
* {{cite journal | vauthors = Beigel JH, Farrar J, Han AM, Hayden FG, Hyer R, de Jong MD, Lochindarat S, Nguyen TK, Nguyen TH, Tran TH, Nicoll A, Touch S, Yuen KY | title = Avian influenza A (H5N1) infection in humans | journal = The New England Journal of Medicine | volume = 353 | issue = 13 | pages = 1374–1385 | date = September 2005 | pmid = 16192482 | doi = 10.1056/NEJMra052211 | hdl-access = free | hdl = 10722/45195 }}
* {{cite journal | vauthors = Ghedin E, Sengamalay NA, Shumway M, Zaborsky J, Feldblyum T, Subbu V, Spiro DJ, Sitz J, Koo H, Bolotov P, Dernovoy D, Tatusova T, Bao Y, St George K, Taylor J, Lipman DJ, Fraser CM, Taubenberger JK, Salzberg SL | title = Large-scale sequencing of human influenza reveals the dynamic nature of viral genome evolution | journal = Nature | volume = 437 | issue = 7062 | pages = 1162–1166 | date = October 2005 | pmid = 16208317 | doi = 10.1038/nature04239 | doi-access = free | bibcode = 2005Natur.437.1162G }} presents a summary of what has been discovered in the [[Influenza Genome Sequencing Project]].
* {{cite journal | vauthors = Hiromoto Y, Yamazaki Y, Fukushima T, Saito T, Lindstrom SE, Omoe K, Nerome R, Lim W, Sugita S, Nerome K | title = Evolutionary characterization of the six internal genes of H5N1 human influenza A virus | journal = The Journal of General Virology | volume = 81 | issue = Pt 5 | pages = 1293–1303 | date = May 2000 | pmid = 10769072 | doi = 10.1099/0022-1317-81-5-1293 | doi-broken-date = 1 November 2024 | doi-access =  }}
{{refend}}

== External links ==
{{refbegin}}
* {{cite web | title = Influenza Report | url = http://www.InfluenzaReport.com | work = InfluenzaReport.com }}
* [https://web.archive.org/web/20060418102354/http://wildlifedisease.nbii.gov/diseasepublications.jsp?disease=Avian%20Influenza Links and descriptions to abstracts and full texts] This bibliography of avian influenza publications was compiled through the cooperative effort of the USGS National Wildlife Health Center and the Wildlife Disease Information Node.
* Search for research publications about H5N1: [https://www.ncbi.nlm.nih.gov/entrez/query.fcgi Entez PubMed]
* Evolutionary "Tree of Life" for H5N1:
** [http://www.nap.edu/books/0309095042/html/79.html Here] is the phylogenetic tree of the influenza virus hemagglutinin gene segment. Amino acid changes in three lineages (bird, pig, human) of the influenza virus hemagglutinin protein segment HA1.
** [http://www.nap.edu/books/0309095042/html/123.html#p2000c2099960123001 Here] is the tree showing the evolution by [[reassortment]] of H5N1 from 1999 to 2004 that created the Z genotype in 2002.
** [https://www.cdc.gov/ncidod/EID/vol11no10/05-0644-G1.htm Here] is the tree showing evolution by [[antigenic drift]] since 2002 that created dozens of highly [[pathogenic]] varieties of the Z genotype of avian flu virus H5N1, some of which are increasingly adapted to mammals.
** [https://web.archive.org/web/20060824004040/http://www.who.int/csr/disease/avian_influenza/guidelines/recommendationvaccine.pdf WHO (PDF) contains latest Evolutionary "Tree of Life" for H5N1] article ''Antigenic and genetic characteristics of H5N1 viruses and candidate H5N1 vaccine viruses developed for potential use as pre-pandemic vaccines'' published August 18, 2006
* [https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=genome&cmd=Retrieve&dopt=Overview&list_uids=18697 Genome database] Page links to the complete sequence of the Influenza A virus (A/Goose/Guangdong/1/96(H5N1)) genome.
{{refend}}

== External links ==
* [http://www.fludb.org Influenza Research Database] – Database of influenza genomic sequences and related information.

{{Influenza}}

{{DEFAULTSORT:H5n1 Genetic Structure}}
[[Category:Influenza A virus subtype H5N1|genetic structure]]