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See also: Influenza A virus subtype H5N1
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). [1] 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 [2] [3]

A/H5N1 virus is shed in the saliva, mucous, and feces of infected birds; other infected animals may shed bird flu viruses in respiratory secretions and other body fluids (such as milk). [4] The virus can spread rapidly through poultry flocks and among wild birds. [4] An estimated half a billion farmed birds have been slaughtered in efforts to contain the virus. [2]

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. [5] [6] Classification as either Low Pathogenic Avian Influenza (LPAI) or High Pathogenic Avian Influenza (HPAI) is based on the severity of symptoms in domestic chickens and does not predict the severity of symptoms in other species. [7] 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. [8]

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. [6] 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. [9] Between 2003 and May 2024, the World Health Organization has recorded 892 cases of confirmed H5N1 influenza, leading to 463 deaths. [10] The true fatality rate may be lower because some cases with mild symptoms may not have been identified as H5N1. [11]

A/H5N1 influenza virus was first identified in farmed birds in southern China in 1996. [12] 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. [13] Some strains of A/H5N1 which are highly pathogenic to chickens have adapted to cause mild symptoms in ducks and geese, [14] [7] and are able to spread rapidly through bird migration. [15] Mammal species that have been recorded with H5N1 infection include cows, seals, goats, and skunks. [16]

Due to the high lethality and virulence of HPAI A(H5N1), its worldwide presence, its increasingly diverse host reservoir, and its significant ongoing mutations, the H5N1 virus is regarded as the world's largest pandemic threat. [17] Domestic poultry may potentially be protected from specific strains of the virus by vaccination. [18] 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. [4] [19] [20]

Terminology

This section is an excerpt from Influenza A virus § Influenza virus nomenclature.

Due to the high variability of the virus, subtyping is not sufficient to uniquely identify a strain of influenza A virus. To unambiguously describe a specific isolate of virus, researchers use the Influenza virus nomenclature, [21] which describes, among other things, the subtype, year, and place of collection. Some examples include: [22]

  • A/Rio de Janeiro/62434/2021 (H3N2). [22]
    • The starting A indicates that the virus is an influenza A virus.
    • Rio de Janeiro indicates the place of collection. 62434 is a laboratory sequence number. 2021 (or just 21) indicates that the sample was collected in 2021. No species is mentioned so by default, the sample was collected from a human.
    • (H3N2) indicates the subtype of the virus.
  • A/swine/South Dakota/152B/2009 (H1N2). [22]
    • This example shows an additional field before the place: swine. It indicates that the sample was collected from a pig.
  • A/California/04/2009 A(H1N1)pdm09. [22]
    • This example carries an unusual designation in the last part: instead of a usual (H1N1), it uses A(H1N1)pdm09. This was in order to distinguish the Pandemic H1N1/09 virus lineage from older H1N1 viruses. [22]
This section is an excerpt from Avian influenza § Highly pathogenic avian influenza.

Because of the impact of avian influenza on economically important chicken farms, a classification system was devised in 1981 which divided avian virus strains as either highly pathogenic (and therefore potentially requiring vigorous control measures) or low pathogenic. The test for this is based solely on the effect on chickens - a virus strain is highly pathogenic avian influenza (HPAI) if 75% or more of chickens die after being deliberately infected with it. The alternative classification is low pathogenic avian influenza (LPAI). [23] This classification system has since been modified to take into account the structure of the virus' haemagglutinin protein. [24] Other species of birds, especially water birds, can become infected with HPAI virus without experiencing severe symptoms and can spread the infection over large distances; the exact symptoms depend on the species of bird and the strain of virus. [23] Classification of an avian virus strain as HPAI or LPAI does not predict how serious the disease might be if it infects humans or other mammals. [23] [25]

Since 2006, the World Organization for Animal Health requires all LPAI H5 and H7 detections to be reported because of their potential to mutate into highly pathogenic strains. [26]

Genome

All influenza A viruses including H5N1 have 11 genes on eight separate RNA segments:[ citation needed]

Two of the most important RNA molecules are HA and PB1. HA creates a surface antigen that is especially important in transmissibility. PB1 creates a viral polymerase molecule that is especially important in virulence.[ citation needed]

The HA RNA molecule contains the HA gene, which codes for hemagglutinin, which is an antigenic glycoprotein found on the surface of the influenza viruses and is responsible for binding the virus to the cell that is being infected. Hemagglutinin forms spikes at the surface of flu viruses that function to attach viruses to 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.[ citation needed]

One genetic factor in distinguishing between human flu viruses and avian flu viruses is that avian influenza HA bind alpha 2-3 sialic acid receptors while human influenza HA bind alpha 2-6 sialic acid receptors. Swine influenza viruses have the ability to bind both types of sialic acid receptors. Humans have avian-type receptors at very low densities and chickens have human-type receptors at very low densities. Some isolates taken from H5N1-infected human have been observed to have HA mutations at positions 182, 192, 223, 226, or 228 and these mutations have been shown to influence the selective binding of the virus to those previously mentioned sialic acid avian and/or human cell surface receptors. These are the types of mutations that can change a bird flu virus into a flu pandemic virus.[ citation needed]

A 2008 virulence study that mated in a laboratory an avian flu H5N1 virus that circulated in Thailand in 2004 and a human flu H3N2 virus recovered in Wyoming in 2003 produced 63 viruses representing various potential combinations of human and avian influenza A virus genes. One in five were lethal to mice at low doses. The virus that most closely matched H5N1 for virulence was one with the hemagglutinin (HA), the neuraminidase (NA) and the PB1 avian flu virus RNA molecules with their genes combined with the remaining five RNA molecules (PB2, PA, NP, M, and NS) with their genes from the human flu virus. Both the viruses from the 1957 pandemic and 1968 pandemic carried an avian flu virus PB1 gene. The authors suggest that picking up an avian flu virus PB1 gene may be a critical step in a potential flu pandemic virus arising through reassortment." [27]

PB1 codes for the PB1 protein and the PB1-F2 protein. The PB1 protein is a critical component of the viral polymerase. The PB1-F2 protein is encoded by an alternative open reading frame of the PB1 RNA segment and "interacts with 2 components of the mitochondrial permeability transition pore complex, ANT3 and VDCA1, [sensitizing] cells to apoptosis. [...] PB1-F2 likely contributes to viral pathogenicity and might have an important role in determining the severity of pandemic influenza." [28] This was discovered by Chen et al. and reported in Nature. [29] "After comparing viruses from the Hong Kong 1997 H5N1 outbreak, one amino acid change (N66S) was found in the PB1-F2 sequence at position 66 that correlated with pathogenicity. This same amino acid change (N66S) was also found in the PB1-F2 protein of the 1918 pandemic A/Brevig Mission/18 virus." [30]

Surface encoding gene segments

All influenza A viruses have two gene segments titled HA and NA which code for the antigenic proteins hemagglutin and neuraminidase which are located on the external envelope of the virus.

HA

HA codes for hemagglutinin, which is an antigenic glycoprotein found on the surface of the influenza viruses and is responsible for binding the virus to the cell that is being infected. Hemagglutinin forms spikes at the surface of flu viruses that function to attach viruses to 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 alpha 2-3 sialic acid receptors while human influenza HA bind alpha 2-6 sialic acid receptors. Swine influenza viruses have the ability to bind both types of sialic acid receptors." [31]

A mutation found in Turkey in 2006 "involves a substitution in one sample of an amino acid at position 223 of the haemoagglutinin receptor protein. This protein allows the flu virus to bind to the receptors on the surface of its host's cells. This mutation has been observed twice before — in a father and son in Hong Kong in 2003, and in one fatal case in Vietnam last year. It increases the virus's ability to bind to human receptors, and decreases its affinity for poultry receptors, making strains with this mutation better adapted to infecting humans."[ according to whom?] Another mutation in the same sample at position 153 has as yet unknown effects. [32]

Recent[ when?] research reveals that humans have avian type receptors at very low densities and chickens have human type receptors at very low densities. [33] Researchers "found that the mutations at two places in the gene, identified as 182 and 192, allow the virus to bind to both bird and human receptors." [34] [35] See research articles Host Range Restriction and Pathogenicity in the Context of Influenza Pandemic (Centers for Disease Control and Prevention, 2006) (by Gabriele Neumann and Yoshihiro Kawaoka) and Structure and Receptor Specificity of the Hemagglutinin from an H5N1 Influenza Virus (American Association for the Advancement of Science, 2006) (by James Stevens, Ola Blixt, Terrence M. Tumpey, Jeffery K. Taubenberger, James C. Paulson, Ian A. Wilson) for further details.

NA

NA codes for neuraminidase which is an antigenic glycoprotein enzyme found on the surface of the influenza viruses. It helps the release of progeny viruses from infected cells. Flu drugs Tamiflu and Relenza work by inhibiting some strains of neuraminidase. They were developed based on N2 and N9. "In the N1 form of the protein, a small segment called the 150-loop is inverted, creating a hollow pocket that does not exist in the N2 and N9 proteins. [...] When the researchers looked at how existing drugs interacted with the N1 protein, they found that, in the presence of neuraminidase inhibitors, the loop changed its conformation to one similar to that in the N2 and N9 proteins." [36]

Internal encoding gene segments

Influenza A viruses have the following RNA segments which code for internal viral proteins: M, NP, NS, PA, PB1, and PB2. [37]

Matrix encoding gene segments

  • 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.
    • M1 is a protein that binds to the viral RNA.
    • M2 is a protein 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. [38] The amino acid substitution (Ser31Asn) in M2 some H5N1 genotypes is associated with amantadine resistance. [39]

Nucleoprotein encoding gene segments.

  • NP codes for nucleoprotein.[ citation needed]
  • NS: NS codes for two nonstructural proteins (NS1 and NS2 - formerly called NEP). "[T]he pathogenicity of influenza virus was related to the nonstructural (NS) gene of the H5N1/97 virus". [40]
    • NS1: Non-structural: nucleus; effects on cellular RNA transport, splicing, translation. Anti-interferon protein. [41] The "NS1 of the highly pathogenic avian H5N1 viruses circulating in poultry and waterfowl in Southeast Asia might be responsible for an enhanced proinflammatory cytokine response (especially TNFa) induced by these viruses in human macrophages". [28] H5N1 NS1 is characterized by a single amino acid change at position 92. By changing the amino acid from glutamic acid to aspartic acid, the researchers were able to abrogate the effect of the H5N1 NS1. [This] single amino acid change in the NS1 gene greatly increased the pathogenicity of the H5N1 influenza virus." [42]
    • NEP: The "nuclear export protein (NEP, formerly referred to as the NS2 protein) mediates the export of vRNPs". [43]

Polymerase encoding gene segments

  • PA codes for the PA protein which is a critical component of the viral polymerase.
  • PB1 codes for the PB1 protein and the PB1-F2 protein.
    • The PB1 protein is a critical component of the viral polymerase.
    • The PB1-F2 protein is encoded by an alternative open reading frame of the PB1 RNA segment and "interacts with 2 components of the mitochondrial permeability transition pore complex, ANT3 and VDCA1, [sensitizing] cells to apoptosis. [...] PB1-F2 likely contributes to viral pathogenicity and might have an important role in determining the severity of pandemic influenza." [28] This was discovered by Chen et al. and reported in Nature. [29] "After comparing viruses from the Hong Kong 1997 H5N1 outbreak, one amino acid change (N66S) was found in the PB1-F2 sequence at position 66 that correlated with pathogenicity. This same amino acid change (N66S) was also found in the PB1-F2 protein of the 1918 pandemic A/Brevig Mission/18 virus." [30]
  • PB2 codes for the PB2 protein which is a critical component of the viral polymerase. As of 2005, 75% of H5N1 human virus isolates from Vietnam had a mutation consisting of Lysine at residue 627 in the PB2 protein; which is believed to cause high levels of virulence. [44] Until H5N1, all known avian influenza viruses had a Glu at position 627, while all human influenza viruses had a lysine. As of 2007, "The emergence of 3 (or more) substrains from the EMA [EMA=Europe, Middle East, Africa] clade represents multiple new opportunities for avian influenza (H5N1) to evolve into a human pandemic strain. In contrast to strains circulating in Southeast Asia, EMA viruses are derived from a progenitor that has the PB2 627K mutation. These viruses are expected to have enhanced replication characteristics in mammals, and indeed the spread of EMA has coincided with the rapid appearance of cases in mammals—including humans in Turkey, Egypt, Iraq, and Djibouti, and cats in Germany, Austria, and Iraq. Unfortunately, the EMA-type viruses appear to be as virulent as the exclusively Asian strains: of 34 human infections outside of Asia through mid-2006, 15 have been fatal." [45] Lys at PB2–627 is believed to confer to avian H5N1 viruses the advantage of efficient growth in the upper and lower respiratory tracts of mammals. [46]

Mutation

This section is an excerpt from Influenza A virus § Pandemic potential.
Influenza viruses have a relatively high mutation rate that is characteristic of RNA viruses. [47] The segmentation of the influenza A virus genome facilitates genetic recombination by segment reassortment in hosts who become infected with two different strains of influenza viruses at the same time. [48] [49] With reassortment between strains, an avian strain which does not affect humans may acquire characteristics from a different strain which enable it to infect and pass between humans - a zoonotic event. [50] It is thought that all influenza A viruses causing outbreaks or pandemics among humans since the 1900s originated from strains circulating in wild aquatic birds through reassortment with other influenza strains. [51] [52] It is possible (though not certain) that pigs may act as an intermediate host for reassortment. [53]
This section is an excerpt from Influenza A virus § Surveillance.
The Global Influenza Surveillance and Response System (GISRS) is a global network of laboratories that monitor the spread of influenza with the aim to provide the World Health Organization with influenza control information and to inform vaccine development. [54] Several millions of specimens are tested by the GISRS network annually through a network of laboratories in 127 countries. [55] As well as human viruses, GISRS monitors avian, swine, and other potentially zoonotic influenza viruses.

See also

References

  1. ^ "Influenza (Avian and other zoonotic)". who.int. World Health Organization. 3 October 2023. Retrieved 2024-05-06.
  2. ^ a b Bourk, India (26 April 2024). "'Unprecedented': How bird flu became an animal pandemic". bbc.com. BBC. Retrieved 2024-05-08.
  3. ^ Shao, Wenhan; Li, Xinxin; Goraya, Mohsan Ullah; Wang, Song; Chen, Ji-Long (2017-08-07). "Evolution of Influenza A Virus by Mutation and Re-Assortment". International Journal of Molecular Sciences. 18 (8): 1650. doi: 10.3390/ijms18081650. ISSN  1422-0067. PMC  5578040. PMID  28783091.
  4. ^ a b c "Prevention and Antiviral Treatment of Bird Flu Viruses in People | Avian Influenza (Flu)". cdc.gov. US: Centers for Disease Control. 2024-04-19. Retrieved 2024-05-08.
  5. ^ "Bird flu (avian influenza)". betterhealth.vic.gov.au. Victoria, Australia: Department of Health & Human Services. Retrieved 2024-05-09.
  6. ^ a b "Avian influenza: guidance, data and analysis". gov.uk. 2021-11-18. Retrieved 2024-05-09.
  7. ^ a b "Avian Influenza in Birds". cdc.gov. US: Centers for Disease Control and Prevention. 2022-06-14. Retrieved 2024-05-06.
  8. ^ "Bird flu (avian influenza): how to spot and report it in poultry or other captive birds". gov.uk. UK: Department for Environment, Food & Rural Affairs and Animal and Plant Health Agency. 2022-12-13. Retrieved 2024-05-06.
  9. ^ "Influenza Type A Viruses". cdc.gov. US: Centers for Disease Control and Prevention. 2024-02-01. Retrieved 2024-05-03.
  10. ^ "Avian influenza A(H5N1) virus". www.who.int. Retrieved 2024-05-28.
  11. ^ Li FC, Choi BC, Sly T, Pak AW (June 2008). "Finding the real case-fatality rate of H5N1 avian influenza". J Epidemiol Community Health. 62 (6): 555–9. doi: 10.1136/jech.2007.064030. PMID  18477756. S2CID  34200426.
  12. ^ "Emergence and Evolution of H5N1 Bird Flu | Avian Influenza (Flu)". cdc.gov. US: Centers for Disease Control and Prevention. 2023-06-06. Retrieved 2024-05-03.
  13. ^ Huang, Pan; Sun, Lujia; Li, Jinhao; et al. (2023-06-16). "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". Cell Discovery. 9 (1): 58. doi: 10.1038/s41421-023-00571-x. ISSN  2056-5968. PMC  10275984. PMID  37328456.
  14. ^ "Highlights in the History of Avian Influenza (Bird Flu) Timeline – 2020-2024 | Avian Influenza (Flu)". cdc.gov. US: Centers for Disease Control and Prevention. 2024-04-22. Retrieved 2024-05-08.
  15. ^ Caliendo, V.; Lewis, N. S.; Pohlmann, A.; et al. (2022-07-11). "Transatlantic spread of highly pathogenic avian influenza H5N1 by wild birds from Europe to North America in 2021". Scientific Reports. 12 (1): 11729. Bibcode: 2022NatSR..1211729C. doi: 10.1038/s41598-022-13447-z. ISSN  2045-2322. PMC  9276711. PMID  35821511.
  16. ^ "Bird flu is bad for poultry and cattle. Why it's not a dire threat for most of us — yet". NBC News. 2024-05-02. Retrieved 2024-05-09.
  17. ^ McKie, Robin (2024-04-20). "Next pandemic likely to be caused by flu virus, scientists warn". The Observer. ISSN  0029-7712. Retrieved 2024-05-09.
  18. ^ "Vaccination of poultry against highly pathogenic avian influenza – Available vaccines and vaccination strategies". efsa.europa.eu. 2023-10-10. Retrieved 2024-05-09.
  19. ^ "Two possible bird flu vaccines could be available within weeks, if needed". NBC News. 2024-05-01. Retrieved 2024-05-09.
  20. ^ "Avian influenza (bird flu) | European Medicines Agency". ema.europa.eu. Retrieved 2024-05-09.
  21. ^ "A revision of the system of nomenclature for influenza viruses: a WHO Memorandum". Bull World Health Organ. 58 (4): 585–591. 1980. PMC  2395936. PMID  6969132. This Memorandum was drafted by the signatories listed on page 590 on the occasion of a meeting held in Geneva in February 1980.
  22. ^ a b c d e "Technical note: Influenza virus nomenclature". Pan American Health Organization. 11 January 2023. Archived from the original on 10 August 2023. Retrieved 27 May 2024.
  23. ^ a b c Alexander DJ, Brown IH (April 2009). "History of highly pathogenic avian influenza". Revue Scientifique et Technique. 28 (1): 19–38. doi: 10.20506/rst.28.1.1856. PMID  19618616.
  24. ^ "Factsheet on A(H5N1)". www.ecdc.europa.eu. 2017-06-15. Retrieved 2024-05-21.
  25. ^ "Current U.S. Bird Flu Situation in Humans". U.S. Centers for Disease Control and Prevention (CDC). 2024-04-05. Retrieved 2024-05-22.
  26. ^ "National H5/H7 Avian Influenza surveillance plan". United States Department of Agriculture. Animal Plant Health Inspection Service. October 2013.
  27. ^ Canadian Press article Study shows hybrids of bird flu and human flu viruses fit well, could occur published June 1, 2008 Archived June 5, 2008, at the Wayback Machine
  28. ^ a b c García-Sastre A (January 2006). "Antiviral response in pandemic influenza viruses". Emerging Infect. Dis. 12 (1): 44–7. doi: 10.3201/eid1201.051186. PMC  3291409. PMID  16494716.
  29. ^ a b Weisan Chen; Paul A. Calvo; et al. (2001). "A novel influenza A virus mitochondrial protein that induces cell death". Nature Medicine. 7 (12): 1306–12. doi: 10.1038/nm1201-1306. PMID  11726970. S2CID  723233.
  30. ^ a b Scientist Live Archived 2007-10-20 at the Wayback Machine article A Single Mutation in the PB1-F2 of H5N1 (HK/97) and 1918 Influenza A Viruses Contributes to Increased Virulence published October 18, 2007
  31. ^ Alex Greninger (July 16, 2004). "The Definition and Measurement of Dangerous Research" (PDF). CISSM Working Paper. Archived from the original (PDF) on November 8, 2006. Retrieved 2006-12-09.
  32. ^ Butler D (January 2006). "Alarms ring over bird flu mutations". Nature. 439 (7074): 248–9. Bibcode: 2006Natur.439..248B. doi: 10.1038/439248a. PMID  16421529.
  33. ^ Influenza Report 2006 Online book page 51
  34. ^ CIDRAP article Study finds 2 mutations that help H5N1 infect humans published November 21, 2006
  35. ^ Bloomberg News articles Two Bird Flu Gene Mutations Might Lead to Faster Human Spread published November 15, 2006
  36. ^ Scidev.net News Archived 2008-02-05 at the Wayback Machine article Bird flu protein's 'pocket' could inspire better drugs published August 16, 2006
  37. ^ "The Threat of Pandemic Influenza: Are We Ready? Page 118".
  38. ^ Influenza virus replication in Medical Microbiology, 4th edition edited by Samuel Baron. 1996 Chapter 58. ISBN  0-9631172-1-1.
  39. ^ Guan Y, Poon LL, Cheung CY, et al. (May 2004). "H5N1 influenza: a protean pandemic threat". Proc. Natl. Acad. Sci. U.S.A. 101 (21): 8156–61. Bibcode: 2004PNAS..101.8156G. doi: 10.1073/pnas.0402443101. PMC  419573. PMID  15148370.
  40. ^ Lee CW, Suarez DL, Tumpey TM, et al. (March 2005). "Characterization of highly pathogenic H5N1 avian influenza A viruses isolated from South Korea". J. Virol. 79 (6): 3692–702. doi: 10.1128/JVI.79.6.3692-3702.2005. PMC  1075707. PMID  15731263.
    Also, Pandemic Influenza Archived 2010-01-06 at the Wayback Machine Center for Infectious Disease Research & Policy Academic Health Center -- University of Minnesota
  41. ^ NS1 described in Inhibition by the NS1 protein - Enhanced virulence/viral pathogenesis by enabling the virus to disarm the host cell type IFN defense system Pathobiologics International
  42. ^ "The Definition and Measurement of Dangerous Research by Alex Greninger" (PDF). Archived from the original (PDF) on 2006-03-06. Retrieved 2006-04-10.
  43. ^ Paragas J, Talon J, O'Neill RE, Anderson DK, García-Sastre A, Palese P (August 2001). "Influenza B and C virus NEP (NS2) proteins possess nuclear export activities". J. Virol. 75 (16): 7375–83. doi: 10.1128/JVI.75.16.7375-7383.2001. PMC  114972. PMID  11462009.
  44. ^ "The Threat of Pandemic Influenza: Are We Ready? Page 126".
  45. ^ Salzberg SL, Kingsford C, Cattoli G, et al. (May 2007). "Genome analysis linking recent European and African influenza (H5N1) viruses". Emerging Infect. Dis. 13 (5): 713–8. doi: 10.3201/eid1305.070013. PMC  2432181. PMID  17553249.
  46. ^ Scientist Live Archived 2007-10-18 at the Wayback Machine article Growth of H5N1 Influenza A Viruses in the Upper Respiratory Tracts of Mice published October 18, 2007
  47. ^ Sanjuán R, Nebot MR, Chirico N, Mansky LM, Belshaw R (October 2010). "Viral mutation rates". Journal of Virology. 84 (19): 9733–48. doi: 10.1128/JVI.00694-10. PMC  2937809. PMID  20660197.
  48. ^ Kou Z, Lei FM, Yu J, Fan ZJ, Yin ZH, Jia CX, Xiong KJ, Sun YH, Zhang XW, Wu XM, Gao XB, Li TX (2005). "New Genotype of Avian Influenza H5N1 Viruses Isolated from Tree Sparrows in China". J. Virol. 79 (24): 15460–15466. doi: 10.1128/JVI.79.24.15460-15466.2005. PMC  1316012. PMID  16306617.
  49. ^ The World Health Organization Global Influenza Program Surveillance Network. (2005). "Evolution of H5N1 avian influenza viruses in Asia". Emerging Infectious Diseases. 11 (10): 1515–1521. doi: 10.3201/eid1110.050644. PMC  3366754. PMID  16318689. Figure 1 shows a diagramatic representation of the genetic relatedness of Asian H5N1 hemagglutinin genes from various isolates of the virus
  50. ^ CDC (2024-05-15). "Transmission of Bird Flu Viruses Between Animals and People". Centers for Disease Control and Prevention. Retrieved 2024-06-10.
  51. ^ Taubenberger, Jeffery K.; Morens, David M. (April 2010). "Influenza: the once and future pandemic". Public Health Reports. 125 (Suppl 3): 16–26. doi: 10.1177/00333549101250S305. ISSN  0033-3549. PMC  2862331. PMID  20568566.
  52. ^ Webster, R. G.; Bean, W. J.; Gorman, O. T.; Chambers, T. M.; Kawaoka, Y. (March 1992). "Evolution and ecology of influenza A viruses". Microbiological Reviews. 56 (1): 152–179. doi: 10.1128/mr.56.1.152-179.1992. ISSN  0146-0749. PMC  372859. PMID  1579108.
  53. ^ "Factsheet on swine influenza in humans and pigs". European Centre for Disease Control. 2017-06-15. Retrieved 2024-06-13.
  54. ^ Lee, Kelley; Fang, Jennifer (2013). Historical Dictionary of the World Health Organization. Rowman & Littlefield. ISBN  9780810878587.
  55. ^ "70 years of GISRS – the Global Influenza Surveillance & Response System". World Health Organization. 19 September 2022. Retrieved 2024-06-13.

Further reading

Retrieved from " https://en.wikipedia.org/?title=H5N1_genetic_structure&oldid=1236474865"
From Wikipedia, the free encyclopedia
See also: Influenza A virus subtype H5N1
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). [1] 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 [2] [3]

A/H5N1 virus is shed in the saliva, mucous, and feces of infected birds; other infected animals may shed bird flu viruses in respiratory secretions and other body fluids (such as milk). [4] The virus can spread rapidly through poultry flocks and among wild birds. [4] An estimated half a billion farmed birds have been slaughtered in efforts to contain the virus. [2]

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. [5] [6] Classification as either Low Pathogenic Avian Influenza (LPAI) or High Pathogenic Avian Influenza (HPAI) is based on the severity of symptoms in domestic chickens and does not predict the severity of symptoms in other species. [7] 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. [8]

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. [6] 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. [9] Between 2003 and May 2024, the World Health Organization has recorded 892 cases of confirmed H5N1 influenza, leading to 463 deaths. [10] The true fatality rate may be lower because some cases with mild symptoms may not have been identified as H5N1. [11]

A/H5N1 influenza virus was first identified in farmed birds in southern China in 1996. [12] 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. [13] Some strains of A/H5N1 which are highly pathogenic to chickens have adapted to cause mild symptoms in ducks and geese, [14] [7] and are able to spread rapidly through bird migration. [15] Mammal species that have been recorded with H5N1 infection include cows, seals, goats, and skunks. [16]

Due to the high lethality and virulence of HPAI A(H5N1), its worldwide presence, its increasingly diverse host reservoir, and its significant ongoing mutations, the H5N1 virus is regarded as the world's largest pandemic threat. [17] Domestic poultry may potentially be protected from specific strains of the virus by vaccination. [18] 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. [4] [19] [20]

Terminology

This section is an excerpt from Influenza A virus § Influenza virus nomenclature.

Due to the high variability of the virus, subtyping is not sufficient to uniquely identify a strain of influenza A virus. To unambiguously describe a specific isolate of virus, researchers use the Influenza virus nomenclature, [21] which describes, among other things, the subtype, year, and place of collection. Some examples include: [22]

  • A/Rio de Janeiro/62434/2021 (H3N2). [22]
    • The starting A indicates that the virus is an influenza A virus.
    • Rio de Janeiro indicates the place of collection. 62434 is a laboratory sequence number. 2021 (or just 21) indicates that the sample was collected in 2021. No species is mentioned so by default, the sample was collected from a human.
    • (H3N2) indicates the subtype of the virus.
  • A/swine/South Dakota/152B/2009 (H1N2). [22]
    • This example shows an additional field before the place: swine. It indicates that the sample was collected from a pig.
  • A/California/04/2009 A(H1N1)pdm09. [22]
    • This example carries an unusual designation in the last part: instead of a usual (H1N1), it uses A(H1N1)pdm09. This was in order to distinguish the Pandemic H1N1/09 virus lineage from older H1N1 viruses. [22]
This section is an excerpt from Avian influenza § Highly pathogenic avian influenza.

Because of the impact of avian influenza on economically important chicken farms, a classification system was devised in 1981 which divided avian virus strains as either highly pathogenic (and therefore potentially requiring vigorous control measures) or low pathogenic. The test for this is based solely on the effect on chickens - a virus strain is highly pathogenic avian influenza (HPAI) if 75% or more of chickens die after being deliberately infected with it. The alternative classification is low pathogenic avian influenza (LPAI). [23] This classification system has since been modified to take into account the structure of the virus' haemagglutinin protein. [24] Other species of birds, especially water birds, can become infected with HPAI virus without experiencing severe symptoms and can spread the infection over large distances; the exact symptoms depend on the species of bird and the strain of virus. [23] Classification of an avian virus strain as HPAI or LPAI does not predict how serious the disease might be if it infects humans or other mammals. [23] [25]

Since 2006, the World Organization for Animal Health requires all LPAI H5 and H7 detections to be reported because of their potential to mutate into highly pathogenic strains. [26]

Genome

All influenza A viruses including H5N1 have 11 genes on eight separate RNA segments:[ citation needed]

Two of the most important RNA molecules are HA and PB1. HA creates a surface antigen that is especially important in transmissibility. PB1 creates a viral polymerase molecule that is especially important in virulence.[ citation needed]

The HA RNA molecule contains the HA gene, which codes for hemagglutinin, which is an antigenic glycoprotein found on the surface of the influenza viruses and is responsible for binding the virus to the cell that is being infected. Hemagglutinin forms spikes at the surface of flu viruses that function to attach viruses to 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.[ citation needed]

One genetic factor in distinguishing between human flu viruses and avian flu viruses is that avian influenza HA bind alpha 2-3 sialic acid receptors while human influenza HA bind alpha 2-6 sialic acid receptors. Swine influenza viruses have the ability to bind both types of sialic acid receptors. Humans have avian-type receptors at very low densities and chickens have human-type receptors at very low densities. Some isolates taken from H5N1-infected human have been observed to have HA mutations at positions 182, 192, 223, 226, or 228 and these mutations have been shown to influence the selective binding of the virus to those previously mentioned sialic acid avian and/or human cell surface receptors. These are the types of mutations that can change a bird flu virus into a flu pandemic virus.[ citation needed]

A 2008 virulence study that mated in a laboratory an avian flu H5N1 virus that circulated in Thailand in 2004 and a human flu H3N2 virus recovered in Wyoming in 2003 produced 63 viruses representing various potential combinations of human and avian influenza A virus genes. One in five were lethal to mice at low doses. The virus that most closely matched H5N1 for virulence was one with the hemagglutinin (HA), the neuraminidase (NA) and the PB1 avian flu virus RNA molecules with their genes combined with the remaining five RNA molecules (PB2, PA, NP, M, and NS) with their genes from the human flu virus. Both the viruses from the 1957 pandemic and 1968 pandemic carried an avian flu virus PB1 gene. The authors suggest that picking up an avian flu virus PB1 gene may be a critical step in a potential flu pandemic virus arising through reassortment." [27]

PB1 codes for the PB1 protein and the PB1-F2 protein. The PB1 protein is a critical component of the viral polymerase. The PB1-F2 protein is encoded by an alternative open reading frame of the PB1 RNA segment and "interacts with 2 components of the mitochondrial permeability transition pore complex, ANT3 and VDCA1, [sensitizing] cells to apoptosis. [...] PB1-F2 likely contributes to viral pathogenicity and might have an important role in determining the severity of pandemic influenza." [28] This was discovered by Chen et al. and reported in Nature. [29] "After comparing viruses from the Hong Kong 1997 H5N1 outbreak, one amino acid change (N66S) was found in the PB1-F2 sequence at position 66 that correlated with pathogenicity. This same amino acid change (N66S) was also found in the PB1-F2 protein of the 1918 pandemic A/Brevig Mission/18 virus." [30]

Surface encoding gene segments

All influenza A viruses have two gene segments titled HA and NA which code for the antigenic proteins hemagglutin and neuraminidase which are located on the external envelope of the virus.

HA

HA codes for hemagglutinin, which is an antigenic glycoprotein found on the surface of the influenza viruses and is responsible for binding the virus to the cell that is being infected. Hemagglutinin forms spikes at the surface of flu viruses that function to attach viruses to 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 alpha 2-3 sialic acid receptors while human influenza HA bind alpha 2-6 sialic acid receptors. Swine influenza viruses have the ability to bind both types of sialic acid receptors." [31]

A mutation found in Turkey in 2006 "involves a substitution in one sample of an amino acid at position 223 of the haemoagglutinin receptor protein. This protein allows the flu virus to bind to the receptors on the surface of its host's cells. This mutation has been observed twice before — in a father and son in Hong Kong in 2003, and in one fatal case in Vietnam last year. It increases the virus's ability to bind to human receptors, and decreases its affinity for poultry receptors, making strains with this mutation better adapted to infecting humans."[ according to whom?] Another mutation in the same sample at position 153 has as yet unknown effects. [32]

Recent[ when?] research reveals that humans have avian type receptors at very low densities and chickens have human type receptors at very low densities. [33] Researchers "found that the mutations at two places in the gene, identified as 182 and 192, allow the virus to bind to both bird and human receptors." [34] [35] See research articles Host Range Restriction and Pathogenicity in the Context of Influenza Pandemic (Centers for Disease Control and Prevention, 2006) (by Gabriele Neumann and Yoshihiro Kawaoka) and Structure and Receptor Specificity of the Hemagglutinin from an H5N1 Influenza Virus (American Association for the Advancement of Science, 2006) (by James Stevens, Ola Blixt, Terrence M. Tumpey, Jeffery K. Taubenberger, James C. Paulson, Ian A. Wilson) for further details.

NA

NA codes for neuraminidase which is an antigenic glycoprotein enzyme found on the surface of the influenza viruses. It helps the release of progeny viruses from infected cells. Flu drugs Tamiflu and Relenza work by inhibiting some strains of neuraminidase. They were developed based on N2 and N9. "In the N1 form of the protein, a small segment called the 150-loop is inverted, creating a hollow pocket that does not exist in the N2 and N9 proteins. [...] When the researchers looked at how existing drugs interacted with the N1 protein, they found that, in the presence of neuraminidase inhibitors, the loop changed its conformation to one similar to that in the N2 and N9 proteins." [36]

Internal encoding gene segments

Influenza A viruses have the following RNA segments which code for internal viral proteins: M, NP, NS, PA, PB1, and PB2. [37]

Matrix encoding gene segments

  • 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.
    • M1 is a protein that binds to the viral RNA.
    • M2 is a protein 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. [38] The amino acid substitution (Ser31Asn) in M2 some H5N1 genotypes is associated with amantadine resistance. [39]

Nucleoprotein encoding gene segments.

  • NP codes for nucleoprotein.[ citation needed]
  • NS: NS codes for two nonstructural proteins (NS1 and NS2 - formerly called NEP). "[T]he pathogenicity of influenza virus was related to the nonstructural (NS) gene of the H5N1/97 virus". [40]
    • NS1: Non-structural: nucleus; effects on cellular RNA transport, splicing, translation. Anti-interferon protein. [41] The "NS1 of the highly pathogenic avian H5N1 viruses circulating in poultry and waterfowl in Southeast Asia might be responsible for an enhanced proinflammatory cytokine response (especially TNFa) induced by these viruses in human macrophages". [28] H5N1 NS1 is characterized by a single amino acid change at position 92. By changing the amino acid from glutamic acid to aspartic acid, the researchers were able to abrogate the effect of the H5N1 NS1. [This] single amino acid change in the NS1 gene greatly increased the pathogenicity of the H5N1 influenza virus." [42]
    • NEP: The "nuclear export protein (NEP, formerly referred to as the NS2 protein) mediates the export of vRNPs". [43]

Polymerase encoding gene segments

  • PA codes for the PA protein which is a critical component of the viral polymerase.
  • PB1 codes for the PB1 protein and the PB1-F2 protein.
    • The PB1 protein is a critical component of the viral polymerase.
    • The PB1-F2 protein is encoded by an alternative open reading frame of the PB1 RNA segment and "interacts with 2 components of the mitochondrial permeability transition pore complex, ANT3 and VDCA1, [sensitizing] cells to apoptosis. [...] PB1-F2 likely contributes to viral pathogenicity and might have an important role in determining the severity of pandemic influenza." [28] This was discovered by Chen et al. and reported in Nature. [29] "After comparing viruses from the Hong Kong 1997 H5N1 outbreak, one amino acid change (N66S) was found in the PB1-F2 sequence at position 66 that correlated with pathogenicity. This same amino acid change (N66S) was also found in the PB1-F2 protein of the 1918 pandemic A/Brevig Mission/18 virus." [30]
  • PB2 codes for the PB2 protein which is a critical component of the viral polymerase. As of 2005, 75% of H5N1 human virus isolates from Vietnam had a mutation consisting of Lysine at residue 627 in the PB2 protein; which is believed to cause high levels of virulence. [44] Until H5N1, all known avian influenza viruses had a Glu at position 627, while all human influenza viruses had a lysine. As of 2007, "The emergence of 3 (or more) substrains from the EMA [EMA=Europe, Middle East, Africa] clade represents multiple new opportunities for avian influenza (H5N1) to evolve into a human pandemic strain. In contrast to strains circulating in Southeast Asia, EMA viruses are derived from a progenitor that has the PB2 627K mutation. These viruses are expected to have enhanced replication characteristics in mammals, and indeed the spread of EMA has coincided with the rapid appearance of cases in mammals—including humans in Turkey, Egypt, Iraq, and Djibouti, and cats in Germany, Austria, and Iraq. Unfortunately, the EMA-type viruses appear to be as virulent as the exclusively Asian strains: of 34 human infections outside of Asia through mid-2006, 15 have been fatal." [45] Lys at PB2–627 is believed to confer to avian H5N1 viruses the advantage of efficient growth in the upper and lower respiratory tracts of mammals. [46]

Mutation

This section is an excerpt from Influenza A virus § Pandemic potential.
Influenza viruses have a relatively high mutation rate that is characteristic of RNA viruses. [47] The segmentation of the influenza A virus genome facilitates genetic recombination by segment reassortment in hosts who become infected with two different strains of influenza viruses at the same time. [48] [49] With reassortment between strains, an avian strain which does not affect humans may acquire characteristics from a different strain which enable it to infect and pass between humans - a zoonotic event. [50] It is thought that all influenza A viruses causing outbreaks or pandemics among humans since the 1900s originated from strains circulating in wild aquatic birds through reassortment with other influenza strains. [51] [52] It is possible (though not certain) that pigs may act as an intermediate host for reassortment. [53]
This section is an excerpt from Influenza A virus § Surveillance.
The Global Influenza Surveillance and Response System (GISRS) is a global network of laboratories that monitor the spread of influenza with the aim to provide the World Health Organization with influenza control information and to inform vaccine development. [54] Several millions of specimens are tested by the GISRS network annually through a network of laboratories in 127 countries. [55] As well as human viruses, GISRS monitors avian, swine, and other potentially zoonotic influenza viruses.

See also

References

  1. ^ "Influenza (Avian and other zoonotic)". who.int. World Health Organization. 3 October 2023. Retrieved 2024-05-06.
  2. ^ a b Bourk, India (26 April 2024). "'Unprecedented': How bird flu became an animal pandemic". bbc.com. BBC. Retrieved 2024-05-08.
  3. ^ Shao, Wenhan; Li, Xinxin; Goraya, Mohsan Ullah; Wang, Song; Chen, Ji-Long (2017-08-07). "Evolution of Influenza A Virus by Mutation and Re-Assortment". International Journal of Molecular Sciences. 18 (8): 1650. doi: 10.3390/ijms18081650. ISSN  1422-0067. PMC  5578040. PMID  28783091.
  4. ^ a b c "Prevention and Antiviral Treatment of Bird Flu Viruses in People | Avian Influenza (Flu)". cdc.gov. US: Centers for Disease Control. 2024-04-19. Retrieved 2024-05-08.
  5. ^ "Bird flu (avian influenza)". betterhealth.vic.gov.au. Victoria, Australia: Department of Health & Human Services. Retrieved 2024-05-09.
  6. ^ a b "Avian influenza: guidance, data and analysis". gov.uk. 2021-11-18. Retrieved 2024-05-09.
  7. ^ a b "Avian Influenza in Birds". cdc.gov. US: Centers for Disease Control and Prevention. 2022-06-14. Retrieved 2024-05-06.
  8. ^ "Bird flu (avian influenza): how to spot and report it in poultry or other captive birds". gov.uk. UK: Department for Environment, Food & Rural Affairs and Animal and Plant Health Agency. 2022-12-13. Retrieved 2024-05-06.
  9. ^ "Influenza Type A Viruses". cdc.gov. US: Centers for Disease Control and Prevention. 2024-02-01. Retrieved 2024-05-03.
  10. ^ "Avian influenza A(H5N1) virus". www.who.int. Retrieved 2024-05-28.
  11. ^ Li FC, Choi BC, Sly T, Pak AW (June 2008). "Finding the real case-fatality rate of H5N1 avian influenza". J Epidemiol Community Health. 62 (6): 555–9. doi: 10.1136/jech.2007.064030. PMID  18477756. S2CID  34200426.
  12. ^ "Emergence and Evolution of H5N1 Bird Flu | Avian Influenza (Flu)". cdc.gov. US: Centers for Disease Control and Prevention. 2023-06-06. Retrieved 2024-05-03.
  13. ^ Huang, Pan; Sun, Lujia; Li, Jinhao; et al. (2023-06-16). "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". Cell Discovery. 9 (1): 58. doi: 10.1038/s41421-023-00571-x. ISSN  2056-5968. PMC  10275984. PMID  37328456.
  14. ^ "Highlights in the History of Avian Influenza (Bird Flu) Timeline – 2020-2024 | Avian Influenza (Flu)". cdc.gov. US: Centers for Disease Control and Prevention. 2024-04-22. Retrieved 2024-05-08.
  15. ^ Caliendo, V.; Lewis, N. S.; Pohlmann, A.; et al. (2022-07-11). "Transatlantic spread of highly pathogenic avian influenza H5N1 by wild birds from Europe to North America in 2021". Scientific Reports. 12 (1): 11729. Bibcode: 2022NatSR..1211729C. doi: 10.1038/s41598-022-13447-z. ISSN  2045-2322. PMC  9276711. PMID  35821511.
  16. ^ "Bird flu is bad for poultry and cattle. Why it's not a dire threat for most of us — yet". NBC News. 2024-05-02. Retrieved 2024-05-09.
  17. ^ McKie, Robin (2024-04-20). "Next pandemic likely to be caused by flu virus, scientists warn". The Observer. ISSN  0029-7712. Retrieved 2024-05-09.
  18. ^ "Vaccination of poultry against highly pathogenic avian influenza – Available vaccines and vaccination strategies". efsa.europa.eu. 2023-10-10. Retrieved 2024-05-09.
  19. ^ "Two possible bird flu vaccines could be available within weeks, if needed". NBC News. 2024-05-01. Retrieved 2024-05-09.
  20. ^ "Avian influenza (bird flu) | European Medicines Agency". ema.europa.eu. Retrieved 2024-05-09.
  21. ^ "A revision of the system of nomenclature for influenza viruses: a WHO Memorandum". Bull World Health Organ. 58 (4): 585–591. 1980. PMC  2395936. PMID  6969132. This Memorandum was drafted by the signatories listed on page 590 on the occasion of a meeting held in Geneva in February 1980.
  22. ^ a b c d e "Technical note: Influenza virus nomenclature". Pan American Health Organization. 11 January 2023. Archived from the original on 10 August 2023. Retrieved 27 May 2024.
  23. ^ a b c Alexander DJ, Brown IH (April 2009). "History of highly pathogenic avian influenza". Revue Scientifique et Technique. 28 (1): 19–38. doi: 10.20506/rst.28.1.1856. PMID  19618616.
  24. ^ "Factsheet on A(H5N1)". www.ecdc.europa.eu. 2017-06-15. Retrieved 2024-05-21.
  25. ^ "Current U.S. Bird Flu Situation in Humans". U.S. Centers for Disease Control and Prevention (CDC). 2024-04-05. Retrieved 2024-05-22.
  26. ^ "National H5/H7 Avian Influenza surveillance plan". United States Department of Agriculture. Animal Plant Health Inspection Service. October 2013.
  27. ^ Canadian Press article Study shows hybrids of bird flu and human flu viruses fit well, could occur published June 1, 2008 Archived June 5, 2008, at the Wayback Machine
  28. ^ a b c García-Sastre A (January 2006). "Antiviral response in pandemic influenza viruses". Emerging Infect. Dis. 12 (1): 44–7. doi: 10.3201/eid1201.051186. PMC  3291409. PMID  16494716.
  29. ^ a b Weisan Chen; Paul A. Calvo; et al. (2001). "A novel influenza A virus mitochondrial protein that induces cell death". Nature Medicine. 7 (12): 1306–12. doi: 10.1038/nm1201-1306. PMID  11726970. S2CID  723233.
  30. ^ a b Scientist Live Archived 2007-10-20 at the Wayback Machine article A Single Mutation in the PB1-F2 of H5N1 (HK/97) and 1918 Influenza A Viruses Contributes to Increased Virulence published October 18, 2007
  31. ^ Alex Greninger (July 16, 2004). "The Definition and Measurement of Dangerous Research" (PDF). CISSM Working Paper. Archived from the original (PDF) on November 8, 2006. Retrieved 2006-12-09.
  32. ^ Butler D (January 2006). "Alarms ring over bird flu mutations". Nature. 439 (7074): 248–9. Bibcode: 2006Natur.439..248B. doi: 10.1038/439248a. PMID  16421529.
  33. ^ Influenza Report 2006 Online book page 51
  34. ^ CIDRAP article Study finds 2 mutations that help H5N1 infect humans published November 21, 2006
  35. ^ Bloomberg News articles Two Bird Flu Gene Mutations Might Lead to Faster Human Spread published November 15, 2006
  36. ^ Scidev.net News Archived 2008-02-05 at the Wayback Machine article Bird flu protein's 'pocket' could inspire better drugs published August 16, 2006
  37. ^ "The Threat of Pandemic Influenza: Are We Ready? Page 118".
  38. ^ Influenza virus replication in Medical Microbiology, 4th edition edited by Samuel Baron. 1996 Chapter 58. ISBN  0-9631172-1-1.
  39. ^ Guan Y, Poon LL, Cheung CY, et al. (May 2004). "H5N1 influenza: a protean pandemic threat". Proc. Natl. Acad. Sci. U.S.A. 101 (21): 8156–61. Bibcode: 2004PNAS..101.8156G. doi: 10.1073/pnas.0402443101. PMC  419573. PMID  15148370.
  40. ^ Lee CW, Suarez DL, Tumpey TM, et al. (March 2005). "Characterization of highly pathogenic H5N1 avian influenza A viruses isolated from South Korea". J. Virol. 79 (6): 3692–702. doi: 10.1128/JVI.79.6.3692-3702.2005. PMC  1075707. PMID  15731263.
    Also, Pandemic Influenza Archived 2010-01-06 at the Wayback Machine Center for Infectious Disease Research & Policy Academic Health Center -- University of Minnesota
  41. ^ NS1 described in Inhibition by the NS1 protein - Enhanced virulence/viral pathogenesis by enabling the virus to disarm the host cell type IFN defense system Pathobiologics International
  42. ^ "The Definition and Measurement of Dangerous Research by Alex Greninger" (PDF). Archived from the original (PDF) on 2006-03-06. Retrieved 2006-04-10.
  43. ^ Paragas J, Talon J, O'Neill RE, Anderson DK, García-Sastre A, Palese P (August 2001). "Influenza B and C virus NEP (NS2) proteins possess nuclear export activities". J. Virol. 75 (16): 7375–83. doi: 10.1128/JVI.75.16.7375-7383.2001. PMC  114972. PMID  11462009.
  44. ^ "The Threat of Pandemic Influenza: Are We Ready? Page 126".
  45. ^ Salzberg SL, Kingsford C, Cattoli G, et al. (May 2007). "Genome analysis linking recent European and African influenza (H5N1) viruses". Emerging Infect. Dis. 13 (5): 713–8. doi: 10.3201/eid1305.070013. PMC  2432181. PMID  17553249.
  46. ^ Scientist Live Archived 2007-10-18 at the Wayback Machine article Growth of H5N1 Influenza A Viruses in the Upper Respiratory Tracts of Mice published October 18, 2007
  47. ^ Sanjuán R, Nebot MR, Chirico N, Mansky LM, Belshaw R (October 2010). "Viral mutation rates". Journal of Virology. 84 (19): 9733–48. doi: 10.1128/JVI.00694-10. PMC  2937809. PMID  20660197.
  48. ^ Kou Z, Lei FM, Yu J, Fan ZJ, Yin ZH, Jia CX, Xiong KJ, Sun YH, Zhang XW, Wu XM, Gao XB, Li TX (2005). "New Genotype of Avian Influenza H5N1 Viruses Isolated from Tree Sparrows in China". J. Virol. 79 (24): 15460–15466. doi: 10.1128/JVI.79.24.15460-15466.2005. PMC  1316012. PMID  16306617.
  49. ^ The World Health Organization Global Influenza Program Surveillance Network. (2005). "Evolution of H5N1 avian influenza viruses in Asia". Emerging Infectious Diseases. 11 (10): 1515–1521. doi: 10.3201/eid1110.050644. PMC  3366754. PMID  16318689. Figure 1 shows a diagramatic representation of the genetic relatedness of Asian H5N1 hemagglutinin genes from various isolates of the virus
  50. ^ CDC (2024-05-15). "Transmission of Bird Flu Viruses Between Animals and People". Centers for Disease Control and Prevention. Retrieved 2024-06-10.
  51. ^ Taubenberger, Jeffery K.; Morens, David M. (April 2010). "Influenza: the once and future pandemic". Public Health Reports. 125 (Suppl 3): 16–26. doi: 10.1177/00333549101250S305. ISSN  0033-3549. PMC  2862331. PMID  20568566.
  52. ^ Webster, R. G.; Bean, W. J.; Gorman, O. T.; Chambers, T. M.; Kawaoka, Y. (March 1992). "Evolution and ecology of influenza A viruses". Microbiological Reviews. 56 (1): 152–179. doi: 10.1128/mr.56.1.152-179.1992. ISSN  0146-0749. PMC  372859. PMID  1579108.
  53. ^ "Factsheet on swine influenza in humans and pigs". European Centre for Disease Control. 2017-06-15. Retrieved 2024-06-13.
  54. ^ Lee, Kelley; Fang, Jennifer (2013). Historical Dictionary of the World Health Organization. Rowman & Littlefield. ISBN  9780810878587.
  55. ^ "70 years of GISRS – the Global Influenza Surveillance & Response System". World Health Organization. 19 September 2022. Retrieved 2024-06-13.

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