H5N1 Genetic Changes Inventory:
A Tool for Influenza Surveillance and Preparedness
The referenced hyperlinks was not provided by CDC (only Author year/PMID) so I did my best last year to find the journal articles, some are available with subscription and some are not!
References for easy viewing!
1 Li et al.2011 PB1-mediated virulence attenuation of H5N1 influenza virus in mice is associated with PB2. J Gen Virol June 2011 vol. 92 no. 6 1435-1444 ; DOI 10.1099/vir.0.030718-0 http://vir.sgmjournals.org/content/9....full.pdf+html
2 Manzoor et al.2009 PB2 Protein of a Highly Pathogenic Avian Influenza Virus Strain A/chicken/Yamaguchi/7/2004 (H5N1) Determines Its Replication Potential in Pigs. J Virol. 2009 Feb;83(4):1572-8. doi: 10.1128/JVI.01879-08
3 Yamada et al.2010 Biological and Structural Characterization of a Host-Adapting Amino Acid in Influenza Virus.PLoS Pathog 6(8): e1001034. doi:10.1371/journal.ppat.1001034 http://www.plospathogens.org/article...l.ppat.1001034
4 Hatta et al. 2007 Growth of H5N1 Influenza A Viruses in the Upper Respiratory Tracts of Mice.PLoS Pathog 3(10): e133. doi:10.1371/journal.ppat.0030133 http://www.plospathogens.org/article...l.ppat.0030133
5 Kim et al. 2010 Role of host-specific amino acids in the pathogenicity of avian H5N1 influenza viruses in mice.Gen Virol May 2010 vol. 91 no. 5 1284-1289, doi: 10.1099/vir.0.018143-0 http://www.plospathogens.org/article...l.ppat.0030133
6 Chen et al.2007 Polygenic virulence factors involved in pathogenesis of 1997 Hong Kong H5N1 influenza viruses in mice.Volume 128, Issues 1–2, September 2007, Pages 159–163, doi.org/10.1016/j.virusres.2007.04.017, http://www.ncbi.nlm.nih.gov/pubmed/17521765 (Abstract)
7 Hatta et al. 2001 Molecular Basis for High Virulence of Hong Kong H5N1 Influenza A Viruses. Science 7 September 2001: 1840-1842 http://www.columbia.edu/itc/biology/...ce293_1840.pdf
8 Shinya et al. PB2 amino acid at position 627 affects replicative efficiency, but not cell tropism, of Hong Kong H5N1 influenza A viruses in mice.Virology. 2004 Mar 15;320(2):258-66. http://www.ncbi.nlm.nih.gov/pubmed/15016548 (Abstract)
9 Fornek et al. 2009 A Single-Amino-Acid Substitution in a Polymerase Protein of an H5N1 Influenza Virus Is Associated with Systemic Infection and Impaired T-Cell Activation in Mice.J. Virol. November 2009 vol. 83 no. 21 11102-11115 doi: 10.1128/JVI.00994-09
10 Le et al. 2009 Selection of H5N1 Influenza Virus PB2 during Replication in Humans.J. Virol. May 2009 vol. 83 no. 10 5278-5281 doi: 10.1128/JVI.00063-09
11 Mase et al. 2006 Recent H5N1 avian Influenza A virus increases rapidly in virulence to mice after a single passage in mice.Gen Virol December 2006 vol. 87 no. 12 3655-3659,doi: 10.1099/vir.0.81843-0 http://vir.sgmjournals.org/content/8....full.pdf+html
12 Bortz et al. 2011 Host- and Strain-Specific Regulation of Influenza Virus Polymerase Activity by Interacting Cellular Proteins.16 August 2011 mBio vol. 2 no. 4 e00151-11 .doi: 10.1128/mBio.00151-11
13 Bogs et al. 2011 Reversion of PB2-627E to -627K during Replication of an H5N1 Clade 2.2 Virus in Mammalian Hosts Depends on the Origin of the Nucleoprotein.J. Virol. October 2011 vol. 85 no. 20 10691-10698; doi: 10.1128/JVI.00786-11
14 Herfst et al. 2012 Airborne Transmission of Influenza A/H5N1 Virus Between Ferrets.Science 336, 1534 (2012);DOI: 10.1126/science.1213362 http://www.sciencemag.org/content/33.../1534.full.pdf
13 Gao et al. 2009 Identification of Amino Acids in HA and PB2 Critical for the Transmission of H5N1 Avian Influenza Viruses in a Mammalian Host.PLoS Pathog 5(12): e1000709. doi:10.1371/journal.ppat.1000709 http://www.plospathogens.org/article...l.ppat.1000252
15 Steel et al. 2009 Transmission of Influenza Virus in a Mammalian Host Is Increased by PB2 Amino Acids 627K or 627E/701N.PLoS Pathog 5(1): e1000252. doi:10.1371/journal.ppat.1000252 http://www.plospathogens.org/article...l.ppat.1000252
16 Li et al. 2005 Molecular Basis of Replication of Duck H5N1 Influenza Viruses in a Mammalian Mouse Model. J Virol. 2005 September; 79(18): 12058–12064. doi: 10.1128/JVI.79.18.12058-12064.2005 http://www.plospathogens.org/article...l.ppat.1000252
17 Leung et al. Correlation between polymerase activity and pathogenicity in two duck H5N1 influenza viruses suggests that the polymerase contributes to pathogenicity.Virology. 2010 May 25;401(1):96-106.PMID: 20211480 http://www.ncbi.nlm.nih.gov/pubmed/20211480 (Abstract)
18 Li J et al. 2009 Single mutation at the amino acid position 627 of PB2 that leads to increased virulence of an H5N1 avian influenza virus during adaptation in mice can be compensated by multiple mutations at other sites of PB2.Virus Res. 2009 Sep;144(1-2):123-9. http://www.ncbi.nlm.nih.gov/pubmed/19393699 (Abstract)
19 D. J. Hulse-Post et al. 2007 Molecular Changes in the Polymerase Genes (PA and PB1) Associated with High Pathogenicity of H5N1 Influenza Virus in Mallard Ducks.J Virol. 2007 August; 81(16): 8515–8524. doi: 10.1128/JVI.00435-07 http://jvi.asm.org/content/81/16/8515.full.pdf+html
20 Salomon et al. 2006 The polymerase complex genes contribute to the high virulence of the human H5N1 influenza virus isolate A/Vietnam/1203/04.J Exp Med. 2006 March 20; 203(3): 689–697.doi: 10.1084/jem.20051938 http://jem.rupress.org/content/203/3/689.full.pdf+html
21 Xu et al. 2012 Amino acids 473V and 598P of PB1 from an avian-origin influenza A virus contribute to polymerase activity, especially in mammalian cells.J Gen Virol. 2012 Mar;93(Pt 3):531-40. http://www.ncbi.nlm.nih.gov/pubmed/22090209 (Abstract)
22 Schmolke M et al. 2011 Differential contribution of PB1-F2 to the virulence of highly pathogenic H5N1 influenza A virus in mammalian and avian species.PLoS Pathog 7(8): e1002186. doi:10.1371/journal.ppat.1002186 http://www.plospathogens.org/article...l.ppat.1002186
23 Conenello GM et al. 2007 Single Mutation in the PB1-F2 of H5N1 (HK/97) and 1918 Influenza A Viruses Contributes to Increased Virulence.PLoS Pathog 3(10): e141. doi:10.1371/journal.ppat.0030141 http://www.plospathogens.org/article...l.ppat.0030141
24 Conenello GM et al. 2011 A single N66S mutation in the PB1-F2 protein of influenza A virus increases virulence by inhibiting the early interferon response in vivo. J. Virol. January 2011 vol. 85 no. 2 652-662.doi: 10.1128/JVI.01987-10
Update 25 Pasricha et al. 2012 Comprehensive global amino acid sequence analysis of PB1F2 protein of influenza A H5N1 viruses and the influenza A virus subtypes responsible for the 20th-century pandemics. DOI: 10.1111/j.1750-2659.2012.00400.x http://onlinelibrary.wiley.com/doi/1...400.x/abstract
25 Su et al. 2008 Analysis of a point mutation in H5N1 avian influenza virus hemagglutinin in relation to virus entry into live mammalian cells.Arch Virol. 2008;153(12):2253-61. http://www.ncbi.nlm.nih.gov/pubmed/19020946 (Abstract)
26 Wang et al. 2010 Glycosylation at 158N of the Hemagglutinin Protein and Receptor Binding Specificity Synergistically Affect the Antigenicity and Immunogenicity of a Live Attenuated H5N1 A/Vietnam/1203/2004 Vaccine Virus in Ferrets.J. Virol. July 2010 vol. 84 no. 13 6570-6577 http://jvi.asm.org/content/84/13/6570.full.pdf+html
27 Yang et al. 2007 Immunization by Avian H5 Influenza Hemagglutinin Mutants with Altered Receptor Binding Specificity Vol. 317 no. 5839 pp. 825-828 DOI: 10.1126/science.1135165 http://www.sciencemag.org/content/317/5839/825
28 Naughtin et al. 2011 Neuraminidase inhibitor sensitivity and receptor-binding specificity of Cambodian clade 1 highly pathogenic H5N1 influenza virus.Antimicrob Agents Chemother. 2011 May; 55(5): 2004–2010.doi: 10.1128/AAC.01773-10 http://aac.asm.org/content/55/5/2004.full.pdf+html
29 Kongchanagul et al. 2008 Positive selection at the receptor-binding site of haemagglutinin H5 in viral sequences derived from human tissues.J Gen Virol. 2008 Aug;89(Pt 8):1805-10.doi: 10.1099/vir.0.2008/002469-0 http://vir.sgmjournals.org/content/89/8/1805.long
30 Yamada et al. 2006 Haemagglutinin mutations responsible for the binding of H5N1 influenza A viruses to human-type receptors.Nature. 2006 Nov 16;444(7117):378-82. http://www.ncbi.nlm.nih.gov/pubmed/17108965 (Abstract)
31 Chen et al. 2012 In vitro evolution of H5N1 avian influenza virus toward human-type receptor specificity.Virology. 2012 Jan 5;422(1):105-13. http://www.ncbi.nlm.nih.gov/pubmed/22056389(Abstract)
32 Chutinimitkul et al. 2010 In vitro assessment of attachment pattern and replication efficiency of H5N1 influenza A viruses with altered receptor specificity.J Virol. 2010 Jul;84(13):6825-33. http://www.ncbi.nlm.nih.gov/pmc/arti...df/2737-09.pdf
33 Watanabe et al. 2011 Acquisition of Human-Type Receptor Binding Specificity by New H5N1 Influenza Virus Sublineages during Their Emergence in Birds in Egypt.PLoS Pathog. 2011 May; 7(5): e1002068. doi: 10.1371/journal.ppat.1002068 http://www.ncbi.nlm.nih.gov/pmc/arti...at.1002068.pdf
34 Manz et al.2010 A polymorphism in the hemagglutinin of the human isolate of a highly pathogenic H5N1 influenza virus determines organ tropism in mice.J Virol. 2010 Aug;84(16):8316-21.doi: 10.1128/JVI.00850-10 http://www.ncbi.nlm.nih.gov/pmc/arti...df/0850-10.pdf
35 Auewarakul et al. 2007 An Avian Influenza H5N1 Virus That Binds to a Human-Type Receptor.J Virol. 2007 September; 81(18): 9950–9955.doi: 10.1128/JVI.00468-07 http://www.ncbi.nlm.nih.gov/pmc/arti...df/0468-07.pdf
36 Gambaryan et al. Evolution of the receptor binding phenotype of influenza A (H5) viruses. Virology. 2006 Jan 20;344(2):432-8. Epub 2005 Oct 13. http://www.ncbi.nlm.nih.gov/pubmed/16226289 (Abstract)
37 Shinya et al. 2010 A mutation in H5 haemagglutinin that conferred human receptor recognition is not maintained stably during duck passage. http://www.ncbi.nlm.nih.gov/pmc/arti...1/?tool=pubmed
38 Stevens et al. 2006 Structure and receptor specificity of the hemagglutinin from an H5N1 influenza virus. Vol. 312 no. 5772 pp. 404-410 ;DOI: 10.1126/science.1124513 http://www.sciencemag.org/content/312/5772/404.long
39 Bosch et al. 1981. Proteolytic cleavage of influenza virus hemagglutinins: primary structure of the connecting peptide between HA1 and HA2 determines proteolytic cleavability and pathogenicity of Avian influenza viruses.Virology. 1981 Sep;113(2):725-35. http://www.sciencedirect.com/science...42682281902014 (Abstract)
40 Perdue et al. 1997 Virulence-associated sequence duplication at the hemagglutinin cleavage site of avian influenza viruses.Virus Res. 1997 Jun;49(2):173-86. http://www.ncbi.nlm.nih.gov/pubmed/9213392 (Abstract)
41 Webster et al. Influenza virus A pathogenicity: the pivotal role of hemagglutinin.Cell. 1987 Aug 28;50(5):665-6. http://www.ncbi.nlm.nih.gov/pubmed/3304656 (Abstract)
42 Subbarao et al. 1998 Characterization of an avian influenza A (H5N1) virus isolated from a child with a fatal respiratory illness.Vol. 279 no. 5349 pp. 393-396 DOI: 10.1126/science.279.5349.393 http://www.sciencemag.org/content/279/5349/393.long
43 Horimoto and Kawaoka et al. 1994 Reverse Genetics Provides Direct Evidence for a Correlation of Hemagglutinin Cleavability and Virulence of an Avian Influenza A Virus. J Virol, May 1994, p. 3120-3128 http://www.ncbi.nlm.nih.gov/pmc/arti...00014-0356.pdf
44 Schrauwen et al.2012 The multibasic cleavage site in H5N1 virus is critical for systemic spread along the olfactory and hematogenous routes in ferrets.J Virol. 2012 Apr;86(7):3975-84. http://www.ncbi.nlm.nih.gov/pubmed/22278228 (Abstract)
45 Sugitan et al.2012 The multibasic cleavage site of the hemagglutinin of highly pathogenic A/Vietnam/1203/2004 (H5N1) avian influenza virus acts as a virulence factor in a host-specific manner in mammals.J Virol. 2012 Mar;86(5):2706-14 http://www.ncbi.nlm.nih.gov/pubmed?term=22205751 (Abstract)
46 Zhang et al. 2012 A Single Amino Acid at the Hemagglutinin Cleavage Site Contributes to the Pathogenicity and Neurovirulence of H5N1 Influenza Virus in Mice. J Virol. 2012 Jun;86(12):6924-31. http://www.ncbi.nlm.nih.gov/pubmed?term=22496231 (Abstract)
47 Reed et al. 2009 Amino Acid Residues in the Fusion Peptide Pocket Regulate the pH of Activation of the H5N1 Influenza Virus Hemagglutinin Protein. J Virol., Apr. 2009, p. 3568–3580 doi: 10.1128/JVI.02238-08
49 Krenn et al. 2011 Single HA2 mutation increases the infectivity and immunogenicity of a live attenuated H5N1 intranasal influenza vaccine candidate lacking NS1.PLoS ONE 6(4): e18577. doi:10.1371/journal.pone.0018577 http://www.ncbi.nlm.nih.gov/pmc/arti...ne.0018577.pdf
50 Ilyushina et al. 2008 Human-Like Receptor Specificity Does Not Affect the Neuraminidase-Inhibitor Susceptibility of H5N1 Influenza Viruses.PLoS Pathog 4(4): e1000043. doi:10.1371/journal.ppat.1000043 http://www.plospathogens.org/article...l.ppat.1000043
51 Yen et al. 2009 Changes in H5N1 influenza virus hemagglutinin receptor binding domain affect systemic spread.Proc Natl Acad Sci U S A. 2009 Jan 6;106(1):286-91 http://www.ncbi.nlm.nih.gov/pmc/arti...pdf/zpq286.pdf
52 Stevens et al. 2008 Recent avian H5N1 viruses exhibit increased propensity for acquiring human receptor specificity.Mol Biol. 2008 September 19; 381(5): 1382–1394. doi:10.1016/j.jmb.2008.04.016. http://www.ncbi.nlm.nih.gov/pmc/arti...nihms47345.pdf
53 Maines et al. 2011 Effect of receptor binding domain mutations on receptor binding and transmissibility of avian influenza H5N1 viruses.Virology. 2011 Apr 25;413(1):139-47. http://www.ncbi.nlm.nih.gov/pubmed/21397290 (Abstract)
54 Harvey et al. 2004 Restrictions to the adaptation of influenza a virus h5 hemagglutinin to the human host. J Virol. 2004 Jan;78(1):502-7. DOI: 10.1128/JVI.78.1.502–507.2004 http://www.ncbi.nlm.nih.gov/pmc/arti...9/pdf/1273.pdf
55 Ramos et al. 2011 Effects of receptor binding specificity of avian influenza virus on the human innate immune response.J Virol. 2011 May;85(9):4421-31. doi:10.1128/JVI.02356-10 http://www.ncbi.nlm.nih.gov/pmc/arti...df/zjv4421.pdf
56 Ayora-Talavera et al. 2009 Mutations in H5N1 influenza virus hemagglutinin that confer binding to human tracheal airway epithelium.PLoS ONE 4(11): e7836. doi:10.1371/journal.pone.0007836 http://www.ncbi.nlm.nih.gov/pmc/arti...ne.0007836.pdf
57 Matsuoka et al. 2009 Neuraminidase stalk length and additional glycosylation of the hemagglutinin influence the virulence of influenza H5N1 viruses for mice. J Virol. 2009 May;83(9):4704-8. doi:10.1128/JVI.01987-08 http://www.ncbi.nlm.nih.gov/pmc/arti...df/1987-08.pdf
58 Zhou et al.2009 The special neuraminidase stalk-motif responsible for increased virulence and pathogenesis of H5N1 influenza A virus. PLoS ONE 4(7): e6277. doi:10.1371/journal.pone.0006277 http://www.ncbi.nlm.nih.gov/pmc/arti...ne.0006277.pdf
59 Hurt et al.2007 Susceptibility of highly pathogenic A(H5N1) avian influenza viruses to the neuraminidase inhibitors and adamantanes.Antiviral Res. 2007 Mar;73(3):228-31 http://www.ncbi.nlm.nih.gov/pubmed/17112602 (Abstract)
60 Boltz et al. 2010 Emergence of H5N1 avian influenza viruses with reduced sensitivity to neuraminidase inhibitors and novel reassortants in Lao People's Democratic Republic.Journal of General Virology (2010), 91, 949–959.DOI 10.1099/vir.0.017459-0 http://www.ncbi.nlm.nih.gov/pmc/arti...58/pdf/949.pdf
61 Ilyushina et al. 2010 Effect of Neuraminidase Inhibitor–Resistant Mutations on Pathogenicity of Clade 2.2 A/Turkey/15/06 (H5N1) Influenza Virus in Ferrets. PLoS Pathog 6(5): e1000933. doi:10.1371/journal.ppat.1000933 http://www.plospathogens.org/article...l.ppat.1000933
62 Le et al.2008 Influenza A H5N1 clade 2.3.4 virus with a different antiviral susceptibility profile replaced clade 1 virus in humans in northern Vietnam.PLoS ONE 3(10): e3339. doi:10.1371/journal.pone.0003339 http://www.plosone.org/article/info:...l.pone.0003339
63 Ilyushina et al.2012 Decreased neuraminidase activity is important for the adaptation of H5N1 influenza virus to human airway epithelium.J Virol. 2012 May;86(9):4724-33. http://www.ncbi.nlm.nih.gov/pubmed/22379077 (Abstract)
64 Hurt et al.2009 In vitro generation of neuraminidase inhibitor resistance in A(H5N1) influenza viruses. Antimicrob Agents Chemother. 2009 Oct;53(10):4433-40.doi:10.1128/AAC.00334-09 http://www.ncbi.nlm.nih.gov/pmc/arti...df/0334-09.pdf
65 Pizzorno et al. 2011 .Generation and Characterization of Recombinant Pandemic Influenza A(H1N1) Viruses Resistant to Neuraminidase Inhibitors. J Infect Dis. 2011 January 1; 203(1): 25–31. doi: 10.1093/infdis/jiq010 http://jid.oxfordjournals.org/content/203/1/25
66 Abed et al. 2006 Impact of neuraminidase mutations conferring influenza resistance to neuraminidase inhibitors in the N1 and N2 genetic backgrounds.Antivir Ther. 2006;11(8):971-6. http://www.ncbi.nlm.nih.gov/pubmed/17302366 (Abstract)
67 Hurt et al. 2010 Assessing the development of oseltamivir and zanamivir resistance in A(H5N1) influenza viruses using a ferret model. Antiviral Res. 2010 Sep;87(3):361-6. http://www.ncbi.nlm.nih.gov/pubmed/20603155 (Abstract)
68 Okomo-Adhiambo et al. 2009 Host cell selection of influenza neuraminidase variants: implications for drug resistance monitoring in A(H1N1) viruses. Antiviral Res. 2010 Feb;85(2):381-8. http://download.thelancet.com/flatco...irology-58.pdf
69 Hurt et al. 2009 Zanamivir-Resistant Influenza Viruses with a Novel Neuraminidase Mutation. J. Virol. 2009, 83(20):10366. DOI: 10.1128/JVI.01200-09. http://jvi.asm.org/content/83/20/10366.full.pdf+html
70 Wibawa et al. 2011
71 Nguyen et al. 2010 Recovery of a multidrug-resistant strain of pandemic influenza A 2009 (H1N1) virus carrying a dual H275Y/I223R mutation from a child after prolonged treatment with oseltamivir.Clin Infect Dis. (2010) 51 (8): 983-984. doi: 10.1086/656439 http://cid.oxfordjournals.org/conten....full.pdf+html
72 Hurt et al. 2011 Increased detection in Australia and Singapore of a novel influenza A(H1N1)2009 variant with reduced oseltamivir and zanamivir sensitivity due to a S247N neuraminidase mutation. http://www.eurosurveillance.org/View...rticleId=19884
73 Gubareva et al. 2001 Selection of influenza virus mutants in experimentally infected volunteers treated with oseltamivir. J Infect Dis. 2001 Feb 15;183(4):523-31.doi: 10.1086/318537 http://jid.oxfordjournals.org/conten....full.pdf+html
74 Le et al. 2005 Avian flu: isolation of drug-resistant H5N1 virus.Nature. 2005 Oct 20;437(7062):1108 http://www.nature.com/nature/journal...f/4371108a.pdf (Abstract)
75 de Jong et al. 2005 Oseltamivir resistance during treatment of influenza A (H5N1) infection.N Engl J Med 2005; 353:2667-2672,De 22, 2005 http://www.nejm.org/doi/full/10.1056...4512#t=article (see Supplementary Material for strains)
76 Govorkova et al. 2007 Efficacy of Oseltamivir Therapy in Ferrets Inoculated with Different Clades of H5N1 Influenza Virus. Antimicrob. Agents Chemother, Apr. 2007, p. 1414–1424.doi:10.1128/AAC.01312-06 http://aac.asm.org/content/51/4/1414.full.pdf+html
77 Iatsyshina et al. 2008 Isolation and molecular characterization of the influenza virus A/H5N1 strains isolated during outbreak of avian influenza among birds in the European part of Russia in 2005: strain with ozeltamivir-resistance mutation was found Mol Gen Mikrobiol Virusol. 2008;(1):26-34. http://www.ncbi.nlm.nih.gov/pubmed/18368779 (Abstract)
78 Hill et al. Evolution of drug resistance in multiple distinct lineages of H5N1 avian influenza.Infect Genet Evol. 2009 Mar;9(2):169-78. http://www.ncbi.nlm.nih.gov/pubmed/19022400 (Abstract)
79 Yen et al. 2007 Neuraminidase inhibitor-resistant recombinant A/Vietnam/1203/04 (H5N1) influenza viruses retain their replication efficiency and pathogenicity in vitro and in vivo.J. Virol. November 2007 vol. 81 no. 22 12418-12426 doi: 10.1128/JVI.01067-07
80 Earhart et al. 2009 Oseltamivir resistance mutation N294S in human influenza A(H5N1) virus in Egypt. J Infect Public Health. 2009;2(2):74-80. http://www.ncbi.nlm.nih.gov/pubmed/20701864 (Abstract)
81 Kiso et al. 2011 Effect of an asparagine-to-serine mutation at position 294 in neuraminidase on the pathogenicity of highly pathogenic H5N1 influenza A virus.J. Virol. May 2011 vol. 85 no. 10 4667-4672 doi: 10.1128/JVI.00047-11
82 Fan et al., 2009 Two amino acid residues in the matrix protein M1 contribute to the virulence difference of H5N1 avian influenza viruses in mice.Virology. 2009 Feb 5;384(1):28-32.doi.org/10.1016/j.virol.2008.11.044 http://www.ncbi.nlm.nih.gov/pubmed/19117585 (Abstract)
83 Smeenk, 1996 Mutations in the hemagglutinin and matrix genes of a virulent influenza virus variant, A/FM/1/47-MA, control different stages in pathogenesis.doi.org/10.1016/0168-1702(96)01329-9 http://www.ncbi.nlm.nih.gov/pubmed/8879138 (Abstract)
84 Brown, 1999 Genetic analysis of mouse-adapted influenza A virus identifies roles for the NA, PB1, and PB2 genes in virulence. doi.org/10.1016/S0168-1702(99)00027-1 http://www.ncbi.nlm.nih.gov/pubmed/10426210 (Abstract)
85 Lan et al., 2010 A comprehensive surveillance of adamantane resistance among human influenza A virus isolated from mainland China between 1956 and 2009. Antivir Ther. 2010;15(6):853-9. http://www.ncbi.nlm.nih.gov/pubmed/20834097 (Abstract)
86 Abed et al. 2005 Generation and characterization of recombinant influenza A (H1N1) viruses harboring amantadine resistance mutations. Antimicrob. Agents Chemother. 2005, 49(2):556. DOI:10.1128/AAC.49.2.556-559.2005. http://aac.asm.org/content/49/2/556.full.pdf+html
87 Cheung et al. 2006 Distribution of amantadine-resistant H5N1 avian influenza variants in Asia. J Infect Dis. 2006 Jun 15;193(12):1626-9.doi: 10.1086/504723 http://jid.oxfordjournals.org/content/193/12/1626.long
88 Ilyushina et al. 2005 Detection of amantadine-resistant variants among avian influenza viruses isolated in North America and Asia. Virology. 2005 Oct 10;341(1):102-6. doi.org/10.1016/j.virol.2005.07.003 http://www.ncbi.nlm.nih.gov/pubmed/16081121 (Abstract)
89 Bean et al. 1989 Biologic potential of amantadine-resistant influenza A virus in an avian model. J Infect Dis. 1989 Jun;159(6):1050-6.doi: 10.1093/infdis/159.6.1050 http://www.ncbi.nlm.nih.gov/pubmed/2723453 (Abstract)
90 He et al. 2008 Amantadine-resistance among H5N1 avian influenza viruses isolated in Northern China. Antiviral Res. 2008 Jan;77(1):72-6. doi.org/10.1016/j.antiviral.2007.08.007 http://www.ncbi.nlm.nih.gov/pubmed/17897729 (Abstract)
91 Cinatl et al. 2007 A Threat of Avian influenza A (h5N1),part III: anitviral therapy Medical Microbiology and Immunology (2007) Volume: 196, Issue: 4, Pages: 203-212 DOI: 10.1007/s00430-007-0048-z http://www.springerlink.com/content/41xpm470518281m7/ (Abstract)
92 Puthavathana et al. 2005 Molecular characterization of the complete genome of human influenza H5N1 virus isolates from Thailand. J. Gen Virol February 2005 vol. 86 no. 2 423-433 doi: 10.1099/vir.0.80368-0 http://vir.sgmjournals.org/content/86/2/423.long
93 Buranathai et al. 2007 Surveillance activities and molecular analysis of H5N1 highly pathogenic avian influenza viruses from Thailand, 2004-2005.Avian Diseases, Volume 51, issue s1 (March 2007), p. 194-200.DOI: 10.1637/7594-040306R.1 http://www.ncbi.nlm.nih.gov/pubmed/17494553 (Abstract)
92 Gabriel et al., 2008 Interaction of Polymerase Subunit PB2 and NP with Importin α1 Is a Determinant of Host Range of Influenza A Virus. PLoS Pathog 4(2): e11. doi:10.1371/journal.ppat.0040011 http://www.plospathogens.org/article...l.ppat.0040011
93 Jiao et al. 2008 A Single-Amino-Acid Substitution in the NS1 Protein Changes the Pathogenicity of H5N1 Avian Influenza Viruses in Mice. J Virol. 2008 February; 82(3): 1146–1154 doi: 10.1128/JVI.01698-07
94 Long et al. 2008 Virulence of H5N1 avian influenza virus enhanced by a 15-nucleotide deletion in the viral nonstructural gene. Virus Genes Volume 36, Number 3 (2008), 471-478, DOI: 10.1007/s11262-007-0187-8 http://www.ncbi.nlm.nih.gov/pubmed/18317917 (Abstract)
95 Seo et al. 2002 Lethal H5N1 influenza viruses escape host anti-viral cytokine responses.Nat Med. 2002 Sep;8(9):950-4. doi:10.1038/nm757 http://www.ncbi.nlm.nih.gov/pubmed/12195436 (abstract)
96 Kuo and Krug et al. 2009 Influenza A Virus Polymerase Is an Integral Component of the CPSF30-NS1A Protein Complex in Infected Cells. J. Virol. February 2009 vol. 83 no. 4 1611-1616 doi: 10.1128/JVI.01491-08
97 Spesock et al. 2011 The Virulence of 1997 H5N1 Influenza Viruses in the Mouse Model Is Increased by Correcting a Defect in Their NS1 Proteins. J. Virol. July 2011 vol. 85 no. 14 7048-7058 http://jvi.asm.org/content/85/14/7048.full.pdf+html
98 Imai et al. 2010 The HA and NS Genes of Human H5N1 Influenza A Virus Contribute to High Virulence in Ferrets. PLoS Pathog 6(9): e1001106. doi:10.1371/journal.ppat.1001106 http://www.plospathogens.org/article...l.ppat.1001106
99 Jackson et al. 2008 A new influenza virus virulence determinant: The NS1 protein four C-terminal residues modulate pathogenicity.PNAS March 18, 2008 vol. 105 no. 11 4381-4386 doi: 10.1073/pnas.0800482105 http://www.pnas.org/content/105/11/4381.full.pdf+html
for NA also see Amino acid substitutions in the NAs of variants in clinical samples or isolates causing reduced antiviral susceptibility www.isirv.org/avg
A Tool for Influenza Surveillance and Preparedness
The referenced hyperlinks was not provided by CDC (only Author year/PMID) so I did my best last year to find the journal articles, some are available with subscription and some are not!
References for easy viewing!
1 Li et al.2011 PB1-mediated virulence attenuation of H5N1 influenza virus in mice is associated with PB2. J Gen Virol June 2011 vol. 92 no. 6 1435-1444 ; DOI 10.1099/vir.0.030718-0 http://vir.sgmjournals.org/content/9....full.pdf+html
2 Manzoor et al.2009 PB2 Protein of a Highly Pathogenic Avian Influenza Virus Strain A/chicken/Yamaguchi/7/2004 (H5N1) Determines Its Replication Potential in Pigs. J Virol. 2009 Feb;83(4):1572-8. doi: 10.1128/JVI.01879-08
3 Yamada et al.2010 Biological and Structural Characterization of a Host-Adapting Amino Acid in Influenza Virus.PLoS Pathog 6(8): e1001034. doi:10.1371/journal.ppat.1001034 http://www.plospathogens.org/article...l.ppat.1001034
4 Hatta et al. 2007 Growth of H5N1 Influenza A Viruses in the Upper Respiratory Tracts of Mice.PLoS Pathog 3(10): e133. doi:10.1371/journal.ppat.0030133 http://www.plospathogens.org/article...l.ppat.0030133
5 Kim et al. 2010 Role of host-specific amino acids in the pathogenicity of avian H5N1 influenza viruses in mice.Gen Virol May 2010 vol. 91 no. 5 1284-1289, doi: 10.1099/vir.0.018143-0 http://www.plospathogens.org/article...l.ppat.0030133
6 Chen et al.2007 Polygenic virulence factors involved in pathogenesis of 1997 Hong Kong H5N1 influenza viruses in mice.Volume 128, Issues 1–2, September 2007, Pages 159–163, doi.org/10.1016/j.virusres.2007.04.017, http://www.ncbi.nlm.nih.gov/pubmed/17521765 (Abstract)
7 Hatta et al. 2001 Molecular Basis for High Virulence of Hong Kong H5N1 Influenza A Viruses. Science 7 September 2001: 1840-1842 http://www.columbia.edu/itc/biology/...ce293_1840.pdf
8 Shinya et al. PB2 amino acid at position 627 affects replicative efficiency, but not cell tropism, of Hong Kong H5N1 influenza A viruses in mice.Virology. 2004 Mar 15;320(2):258-66. http://www.ncbi.nlm.nih.gov/pubmed/15016548 (Abstract)
9 Fornek et al. 2009 A Single-Amino-Acid Substitution in a Polymerase Protein of an H5N1 Influenza Virus Is Associated with Systemic Infection and Impaired T-Cell Activation in Mice.J. Virol. November 2009 vol. 83 no. 21 11102-11115 doi: 10.1128/JVI.00994-09
10 Le et al. 2009 Selection of H5N1 Influenza Virus PB2 during Replication in Humans.J. Virol. May 2009 vol. 83 no. 10 5278-5281 doi: 10.1128/JVI.00063-09
11 Mase et al. 2006 Recent H5N1 avian Influenza A virus increases rapidly in virulence to mice after a single passage in mice.Gen Virol December 2006 vol. 87 no. 12 3655-3659,doi: 10.1099/vir.0.81843-0 http://vir.sgmjournals.org/content/8....full.pdf+html
12 Bortz et al. 2011 Host- and Strain-Specific Regulation of Influenza Virus Polymerase Activity by Interacting Cellular Proteins.16 August 2011 mBio vol. 2 no. 4 e00151-11 .doi: 10.1128/mBio.00151-11
13 Bogs et al. 2011 Reversion of PB2-627E to -627K during Replication of an H5N1 Clade 2.2 Virus in Mammalian Hosts Depends on the Origin of the Nucleoprotein.J. Virol. October 2011 vol. 85 no. 20 10691-10698; doi: 10.1128/JVI.00786-11
14 Herfst et al. 2012 Airborne Transmission of Influenza A/H5N1 Virus Between Ferrets.Science 336, 1534 (2012);DOI: 10.1126/science.1213362 http://www.sciencemag.org/content/33.../1534.full.pdf
13 Gao et al. 2009 Identification of Amino Acids in HA and PB2 Critical for the Transmission of H5N1 Avian Influenza Viruses in a Mammalian Host.PLoS Pathog 5(12): e1000709. doi:10.1371/journal.ppat.1000709 http://www.plospathogens.org/article...l.ppat.1000252
15 Steel et al. 2009 Transmission of Influenza Virus in a Mammalian Host Is Increased by PB2 Amino Acids 627K or 627E/701N.PLoS Pathog 5(1): e1000252. doi:10.1371/journal.ppat.1000252 http://www.plospathogens.org/article...l.ppat.1000252
16 Li et al. 2005 Molecular Basis of Replication of Duck H5N1 Influenza Viruses in a Mammalian Mouse Model. J Virol. 2005 September; 79(18): 12058–12064. doi: 10.1128/JVI.79.18.12058-12064.2005 http://www.plospathogens.org/article...l.ppat.1000252
17 Leung et al. Correlation between polymerase activity and pathogenicity in two duck H5N1 influenza viruses suggests that the polymerase contributes to pathogenicity.Virology. 2010 May 25;401(1):96-106.PMID: 20211480 http://www.ncbi.nlm.nih.gov/pubmed/20211480 (Abstract)
18 Li J et al. 2009 Single mutation at the amino acid position 627 of PB2 that leads to increased virulence of an H5N1 avian influenza virus during adaptation in mice can be compensated by multiple mutations at other sites of PB2.Virus Res. 2009 Sep;144(1-2):123-9. http://www.ncbi.nlm.nih.gov/pubmed/19393699 (Abstract)
19 D. J. Hulse-Post et al. 2007 Molecular Changes in the Polymerase Genes (PA and PB1) Associated with High Pathogenicity of H5N1 Influenza Virus in Mallard Ducks.J Virol. 2007 August; 81(16): 8515–8524. doi: 10.1128/JVI.00435-07 http://jvi.asm.org/content/81/16/8515.full.pdf+html
20 Salomon et al. 2006 The polymerase complex genes contribute to the high virulence of the human H5N1 influenza virus isolate A/Vietnam/1203/04.J Exp Med. 2006 March 20; 203(3): 689–697.doi: 10.1084/jem.20051938 http://jem.rupress.org/content/203/3/689.full.pdf+html
21 Xu et al. 2012 Amino acids 473V and 598P of PB1 from an avian-origin influenza A virus contribute to polymerase activity, especially in mammalian cells.J Gen Virol. 2012 Mar;93(Pt 3):531-40. http://www.ncbi.nlm.nih.gov/pubmed/22090209 (Abstract)
22 Schmolke M et al. 2011 Differential contribution of PB1-F2 to the virulence of highly pathogenic H5N1 influenza A virus in mammalian and avian species.PLoS Pathog 7(8): e1002186. doi:10.1371/journal.ppat.1002186 http://www.plospathogens.org/article...l.ppat.1002186
23 Conenello GM et al. 2007 Single Mutation in the PB1-F2 of H5N1 (HK/97) and 1918 Influenza A Viruses Contributes to Increased Virulence.PLoS Pathog 3(10): e141. doi:10.1371/journal.ppat.0030141 http://www.plospathogens.org/article...l.ppat.0030141
24 Conenello GM et al. 2011 A single N66S mutation in the PB1-F2 protein of influenza A virus increases virulence by inhibiting the early interferon response in vivo. J. Virol. January 2011 vol. 85 no. 2 652-662.doi: 10.1128/JVI.01987-10
Update 25 Pasricha et al. 2012 Comprehensive global amino acid sequence analysis of PB1F2 protein of influenza A H5N1 viruses and the influenza A virus subtypes responsible for the 20th-century pandemics. DOI: 10.1111/j.1750-2659.2012.00400.x http://onlinelibrary.wiley.com/doi/1...400.x/abstract
25 Su et al. 2008 Analysis of a point mutation in H5N1 avian influenza virus hemagglutinin in relation to virus entry into live mammalian cells.Arch Virol. 2008;153(12):2253-61. http://www.ncbi.nlm.nih.gov/pubmed/19020946 (Abstract)
26 Wang et al. 2010 Glycosylation at 158N of the Hemagglutinin Protein and Receptor Binding Specificity Synergistically Affect the Antigenicity and Immunogenicity of a Live Attenuated H5N1 A/Vietnam/1203/2004 Vaccine Virus in Ferrets.J. Virol. July 2010 vol. 84 no. 13 6570-6577 http://jvi.asm.org/content/84/13/6570.full.pdf+html
27 Yang et al. 2007 Immunization by Avian H5 Influenza Hemagglutinin Mutants with Altered Receptor Binding Specificity Vol. 317 no. 5839 pp. 825-828 DOI: 10.1126/science.1135165 http://www.sciencemag.org/content/317/5839/825
28 Naughtin et al. 2011 Neuraminidase inhibitor sensitivity and receptor-binding specificity of Cambodian clade 1 highly pathogenic H5N1 influenza virus.Antimicrob Agents Chemother. 2011 May; 55(5): 2004–2010.doi: 10.1128/AAC.01773-10 http://aac.asm.org/content/55/5/2004.full.pdf+html
29 Kongchanagul et al. 2008 Positive selection at the receptor-binding site of haemagglutinin H5 in viral sequences derived from human tissues.J Gen Virol. 2008 Aug;89(Pt 8):1805-10.doi: 10.1099/vir.0.2008/002469-0 http://vir.sgmjournals.org/content/89/8/1805.long
30 Yamada et al. 2006 Haemagglutinin mutations responsible for the binding of H5N1 influenza A viruses to human-type receptors.Nature. 2006 Nov 16;444(7117):378-82. http://www.ncbi.nlm.nih.gov/pubmed/17108965 (Abstract)
31 Chen et al. 2012 In vitro evolution of H5N1 avian influenza virus toward human-type receptor specificity.Virology. 2012 Jan 5;422(1):105-13. http://www.ncbi.nlm.nih.gov/pubmed/22056389(Abstract)
32 Chutinimitkul et al. 2010 In vitro assessment of attachment pattern and replication efficiency of H5N1 influenza A viruses with altered receptor specificity.J Virol. 2010 Jul;84(13):6825-33. http://www.ncbi.nlm.nih.gov/pmc/arti...df/2737-09.pdf
33 Watanabe et al. 2011 Acquisition of Human-Type Receptor Binding Specificity by New H5N1 Influenza Virus Sublineages during Their Emergence in Birds in Egypt.PLoS Pathog. 2011 May; 7(5): e1002068. doi: 10.1371/journal.ppat.1002068 http://www.ncbi.nlm.nih.gov/pmc/arti...at.1002068.pdf
34 Manz et al.2010 A polymorphism in the hemagglutinin of the human isolate of a highly pathogenic H5N1 influenza virus determines organ tropism in mice.J Virol. 2010 Aug;84(16):8316-21.doi: 10.1128/JVI.00850-10 http://www.ncbi.nlm.nih.gov/pmc/arti...df/0850-10.pdf
35 Auewarakul et al. 2007 An Avian Influenza H5N1 Virus That Binds to a Human-Type Receptor.J Virol. 2007 September; 81(18): 9950–9955.doi: 10.1128/JVI.00468-07 http://www.ncbi.nlm.nih.gov/pmc/arti...df/0468-07.pdf
36 Gambaryan et al. Evolution of the receptor binding phenotype of influenza A (H5) viruses. Virology. 2006 Jan 20;344(2):432-8. Epub 2005 Oct 13. http://www.ncbi.nlm.nih.gov/pubmed/16226289 (Abstract)
37 Shinya et al. 2010 A mutation in H5 haemagglutinin that conferred human receptor recognition is not maintained stably during duck passage. http://www.ncbi.nlm.nih.gov/pmc/arti...1/?tool=pubmed
38 Stevens et al. 2006 Structure and receptor specificity of the hemagglutinin from an H5N1 influenza virus. Vol. 312 no. 5772 pp. 404-410 ;DOI: 10.1126/science.1124513 http://www.sciencemag.org/content/312/5772/404.long
39 Bosch et al. 1981. Proteolytic cleavage of influenza virus hemagglutinins: primary structure of the connecting peptide between HA1 and HA2 determines proteolytic cleavability and pathogenicity of Avian influenza viruses.Virology. 1981 Sep;113(2):725-35. http://www.sciencedirect.com/science...42682281902014 (Abstract)
40 Perdue et al. 1997 Virulence-associated sequence duplication at the hemagglutinin cleavage site of avian influenza viruses.Virus Res. 1997 Jun;49(2):173-86. http://www.ncbi.nlm.nih.gov/pubmed/9213392 (Abstract)
41 Webster et al. Influenza virus A pathogenicity: the pivotal role of hemagglutinin.Cell. 1987 Aug 28;50(5):665-6. http://www.ncbi.nlm.nih.gov/pubmed/3304656 (Abstract)
42 Subbarao et al. 1998 Characterization of an avian influenza A (H5N1) virus isolated from a child with a fatal respiratory illness.Vol. 279 no. 5349 pp. 393-396 DOI: 10.1126/science.279.5349.393 http://www.sciencemag.org/content/279/5349/393.long
43 Horimoto and Kawaoka et al. 1994 Reverse Genetics Provides Direct Evidence for a Correlation of Hemagglutinin Cleavability and Virulence of an Avian Influenza A Virus. J Virol, May 1994, p. 3120-3128 http://www.ncbi.nlm.nih.gov/pmc/arti...00014-0356.pdf
44 Schrauwen et al.2012 The multibasic cleavage site in H5N1 virus is critical for systemic spread along the olfactory and hematogenous routes in ferrets.J Virol. 2012 Apr;86(7):3975-84. http://www.ncbi.nlm.nih.gov/pubmed/22278228 (Abstract)
45 Sugitan et al.2012 The multibasic cleavage site of the hemagglutinin of highly pathogenic A/Vietnam/1203/2004 (H5N1) avian influenza virus acts as a virulence factor in a host-specific manner in mammals.J Virol. 2012 Mar;86(5):2706-14 http://www.ncbi.nlm.nih.gov/pubmed?term=22205751 (Abstract)
46 Zhang et al. 2012 A Single Amino Acid at the Hemagglutinin Cleavage Site Contributes to the Pathogenicity and Neurovirulence of H5N1 Influenza Virus in Mice. J Virol. 2012 Jun;86(12):6924-31. http://www.ncbi.nlm.nih.gov/pubmed?term=22496231 (Abstract)
47 Reed et al. 2009 Amino Acid Residues in the Fusion Peptide Pocket Regulate the pH of Activation of the H5N1 Influenza Virus Hemagglutinin Protein. J Virol., Apr. 2009, p. 3568–3580 doi: 10.1128/JVI.02238-08
49 Krenn et al. 2011 Single HA2 mutation increases the infectivity and immunogenicity of a live attenuated H5N1 intranasal influenza vaccine candidate lacking NS1.PLoS ONE 6(4): e18577. doi:10.1371/journal.pone.0018577 http://www.ncbi.nlm.nih.gov/pmc/arti...ne.0018577.pdf
50 Ilyushina et al. 2008 Human-Like Receptor Specificity Does Not Affect the Neuraminidase-Inhibitor Susceptibility of H5N1 Influenza Viruses.PLoS Pathog 4(4): e1000043. doi:10.1371/journal.ppat.1000043 http://www.plospathogens.org/article...l.ppat.1000043
51 Yen et al. 2009 Changes in H5N1 influenza virus hemagglutinin receptor binding domain affect systemic spread.Proc Natl Acad Sci U S A. 2009 Jan 6;106(1):286-91 http://www.ncbi.nlm.nih.gov/pmc/arti...pdf/zpq286.pdf
52 Stevens et al. 2008 Recent avian H5N1 viruses exhibit increased propensity for acquiring human receptor specificity.Mol Biol. 2008 September 19; 381(5): 1382–1394. doi:10.1016/j.jmb.2008.04.016. http://www.ncbi.nlm.nih.gov/pmc/arti...nihms47345.pdf
53 Maines et al. 2011 Effect of receptor binding domain mutations on receptor binding and transmissibility of avian influenza H5N1 viruses.Virology. 2011 Apr 25;413(1):139-47. http://www.ncbi.nlm.nih.gov/pubmed/21397290 (Abstract)
54 Harvey et al. 2004 Restrictions to the adaptation of influenza a virus h5 hemagglutinin to the human host. J Virol. 2004 Jan;78(1):502-7. DOI: 10.1128/JVI.78.1.502–507.2004 http://www.ncbi.nlm.nih.gov/pmc/arti...9/pdf/1273.pdf
55 Ramos et al. 2011 Effects of receptor binding specificity of avian influenza virus on the human innate immune response.J Virol. 2011 May;85(9):4421-31. doi:10.1128/JVI.02356-10 http://www.ncbi.nlm.nih.gov/pmc/arti...df/zjv4421.pdf
56 Ayora-Talavera et al. 2009 Mutations in H5N1 influenza virus hemagglutinin that confer binding to human tracheal airway epithelium.PLoS ONE 4(11): e7836. doi:10.1371/journal.pone.0007836 http://www.ncbi.nlm.nih.gov/pmc/arti...ne.0007836.pdf
57 Matsuoka et al. 2009 Neuraminidase stalk length and additional glycosylation of the hemagglutinin influence the virulence of influenza H5N1 viruses for mice. J Virol. 2009 May;83(9):4704-8. doi:10.1128/JVI.01987-08 http://www.ncbi.nlm.nih.gov/pmc/arti...df/1987-08.pdf
58 Zhou et al.2009 The special neuraminidase stalk-motif responsible for increased virulence and pathogenesis of H5N1 influenza A virus. PLoS ONE 4(7): e6277. doi:10.1371/journal.pone.0006277 http://www.ncbi.nlm.nih.gov/pmc/arti...ne.0006277.pdf
59 Hurt et al.2007 Susceptibility of highly pathogenic A(H5N1) avian influenza viruses to the neuraminidase inhibitors and adamantanes.Antiviral Res. 2007 Mar;73(3):228-31 http://www.ncbi.nlm.nih.gov/pubmed/17112602 (Abstract)
60 Boltz et al. 2010 Emergence of H5N1 avian influenza viruses with reduced sensitivity to neuraminidase inhibitors and novel reassortants in Lao People's Democratic Republic.Journal of General Virology (2010), 91, 949–959.DOI 10.1099/vir.0.017459-0 http://www.ncbi.nlm.nih.gov/pmc/arti...58/pdf/949.pdf
61 Ilyushina et al. 2010 Effect of Neuraminidase Inhibitor–Resistant Mutations on Pathogenicity of Clade 2.2 A/Turkey/15/06 (H5N1) Influenza Virus in Ferrets. PLoS Pathog 6(5): e1000933. doi:10.1371/journal.ppat.1000933 http://www.plospathogens.org/article...l.ppat.1000933
62 Le et al.2008 Influenza A H5N1 clade 2.3.4 virus with a different antiviral susceptibility profile replaced clade 1 virus in humans in northern Vietnam.PLoS ONE 3(10): e3339. doi:10.1371/journal.pone.0003339 http://www.plosone.org/article/info:...l.pone.0003339
63 Ilyushina et al.2012 Decreased neuraminidase activity is important for the adaptation of H5N1 influenza virus to human airway epithelium.J Virol. 2012 May;86(9):4724-33. http://www.ncbi.nlm.nih.gov/pubmed/22379077 (Abstract)
64 Hurt et al.2009 In vitro generation of neuraminidase inhibitor resistance in A(H5N1) influenza viruses. Antimicrob Agents Chemother. 2009 Oct;53(10):4433-40.doi:10.1128/AAC.00334-09 http://www.ncbi.nlm.nih.gov/pmc/arti...df/0334-09.pdf
65 Pizzorno et al. 2011 .Generation and Characterization of Recombinant Pandemic Influenza A(H1N1) Viruses Resistant to Neuraminidase Inhibitors. J Infect Dis. 2011 January 1; 203(1): 25–31. doi: 10.1093/infdis/jiq010 http://jid.oxfordjournals.org/content/203/1/25
66 Abed et al. 2006 Impact of neuraminidase mutations conferring influenza resistance to neuraminidase inhibitors in the N1 and N2 genetic backgrounds.Antivir Ther. 2006;11(8):971-6. http://www.ncbi.nlm.nih.gov/pubmed/17302366 (Abstract)
67 Hurt et al. 2010 Assessing the development of oseltamivir and zanamivir resistance in A(H5N1) influenza viruses using a ferret model. Antiviral Res. 2010 Sep;87(3):361-6. http://www.ncbi.nlm.nih.gov/pubmed/20603155 (Abstract)
68 Okomo-Adhiambo et al. 2009 Host cell selection of influenza neuraminidase variants: implications for drug resistance monitoring in A(H1N1) viruses. Antiviral Res. 2010 Feb;85(2):381-8. http://download.thelancet.com/flatco...irology-58.pdf
69 Hurt et al. 2009 Zanamivir-Resistant Influenza Viruses with a Novel Neuraminidase Mutation. J. Virol. 2009, 83(20):10366. DOI: 10.1128/JVI.01200-09. http://jvi.asm.org/content/83/20/10366.full.pdf+html
70 Wibawa et al. 2011
71 Nguyen et al. 2010 Recovery of a multidrug-resistant strain of pandemic influenza A 2009 (H1N1) virus carrying a dual H275Y/I223R mutation from a child after prolonged treatment with oseltamivir.Clin Infect Dis. (2010) 51 (8): 983-984. doi: 10.1086/656439 http://cid.oxfordjournals.org/conten....full.pdf+html
72 Hurt et al. 2011 Increased detection in Australia and Singapore of a novel influenza A(H1N1)2009 variant with reduced oseltamivir and zanamivir sensitivity due to a S247N neuraminidase mutation. http://www.eurosurveillance.org/View...rticleId=19884
73 Gubareva et al. 2001 Selection of influenza virus mutants in experimentally infected volunteers treated with oseltamivir. J Infect Dis. 2001 Feb 15;183(4):523-31.doi: 10.1086/318537 http://jid.oxfordjournals.org/conten....full.pdf+html
74 Le et al. 2005 Avian flu: isolation of drug-resistant H5N1 virus.Nature. 2005 Oct 20;437(7062):1108 http://www.nature.com/nature/journal...f/4371108a.pdf (Abstract)
75 de Jong et al. 2005 Oseltamivir resistance during treatment of influenza A (H5N1) infection.N Engl J Med 2005; 353:2667-2672,De 22, 2005 http://www.nejm.org/doi/full/10.1056...4512#t=article (see Supplementary Material for strains)
76 Govorkova et al. 2007 Efficacy of Oseltamivir Therapy in Ferrets Inoculated with Different Clades of H5N1 Influenza Virus. Antimicrob. Agents Chemother, Apr. 2007, p. 1414–1424.doi:10.1128/AAC.01312-06 http://aac.asm.org/content/51/4/1414.full.pdf+html
77 Iatsyshina et al. 2008 Isolation and molecular characterization of the influenza virus A/H5N1 strains isolated during outbreak of avian influenza among birds in the European part of Russia in 2005: strain with ozeltamivir-resistance mutation was found Mol Gen Mikrobiol Virusol. 2008;(1):26-34. http://www.ncbi.nlm.nih.gov/pubmed/18368779 (Abstract)
78 Hill et al. Evolution of drug resistance in multiple distinct lineages of H5N1 avian influenza.Infect Genet Evol. 2009 Mar;9(2):169-78. http://www.ncbi.nlm.nih.gov/pubmed/19022400 (Abstract)
79 Yen et al. 2007 Neuraminidase inhibitor-resistant recombinant A/Vietnam/1203/04 (H5N1) influenza viruses retain their replication efficiency and pathogenicity in vitro and in vivo.J. Virol. November 2007 vol. 81 no. 22 12418-12426 doi: 10.1128/JVI.01067-07
80 Earhart et al. 2009 Oseltamivir resistance mutation N294S in human influenza A(H5N1) virus in Egypt. J Infect Public Health. 2009;2(2):74-80. http://www.ncbi.nlm.nih.gov/pubmed/20701864 (Abstract)
81 Kiso et al. 2011 Effect of an asparagine-to-serine mutation at position 294 in neuraminidase on the pathogenicity of highly pathogenic H5N1 influenza A virus.J. Virol. May 2011 vol. 85 no. 10 4667-4672 doi: 10.1128/JVI.00047-11
82 Fan et al., 2009 Two amino acid residues in the matrix protein M1 contribute to the virulence difference of H5N1 avian influenza viruses in mice.Virology. 2009 Feb 5;384(1):28-32.doi.org/10.1016/j.virol.2008.11.044 http://www.ncbi.nlm.nih.gov/pubmed/19117585 (Abstract)
83 Smeenk, 1996 Mutations in the hemagglutinin and matrix genes of a virulent influenza virus variant, A/FM/1/47-MA, control different stages in pathogenesis.doi.org/10.1016/0168-1702(96)01329-9 http://www.ncbi.nlm.nih.gov/pubmed/8879138 (Abstract)
84 Brown, 1999 Genetic analysis of mouse-adapted influenza A virus identifies roles for the NA, PB1, and PB2 genes in virulence. doi.org/10.1016/S0168-1702(99)00027-1 http://www.ncbi.nlm.nih.gov/pubmed/10426210 (Abstract)
85 Lan et al., 2010 A comprehensive surveillance of adamantane resistance among human influenza A virus isolated from mainland China between 1956 and 2009. Antivir Ther. 2010;15(6):853-9. http://www.ncbi.nlm.nih.gov/pubmed/20834097 (Abstract)
86 Abed et al. 2005 Generation and characterization of recombinant influenza A (H1N1) viruses harboring amantadine resistance mutations. Antimicrob. Agents Chemother. 2005, 49(2):556. DOI:10.1128/AAC.49.2.556-559.2005. http://aac.asm.org/content/49/2/556.full.pdf+html
87 Cheung et al. 2006 Distribution of amantadine-resistant H5N1 avian influenza variants in Asia. J Infect Dis. 2006 Jun 15;193(12):1626-9.doi: 10.1086/504723 http://jid.oxfordjournals.org/content/193/12/1626.long
88 Ilyushina et al. 2005 Detection of amantadine-resistant variants among avian influenza viruses isolated in North America and Asia. Virology. 2005 Oct 10;341(1):102-6. doi.org/10.1016/j.virol.2005.07.003 http://www.ncbi.nlm.nih.gov/pubmed/16081121 (Abstract)
89 Bean et al. 1989 Biologic potential of amantadine-resistant influenza A virus in an avian model. J Infect Dis. 1989 Jun;159(6):1050-6.doi: 10.1093/infdis/159.6.1050 http://www.ncbi.nlm.nih.gov/pubmed/2723453 (Abstract)
90 He et al. 2008 Amantadine-resistance among H5N1 avian influenza viruses isolated in Northern China. Antiviral Res. 2008 Jan;77(1):72-6. doi.org/10.1016/j.antiviral.2007.08.007 http://www.ncbi.nlm.nih.gov/pubmed/17897729 (Abstract)
91 Cinatl et al. 2007 A Threat of Avian influenza A (h5N1),part III: anitviral therapy Medical Microbiology and Immunology (2007) Volume: 196, Issue: 4, Pages: 203-212 DOI: 10.1007/s00430-007-0048-z http://www.springerlink.com/content/41xpm470518281m7/ (Abstract)
92 Puthavathana et al. 2005 Molecular characterization of the complete genome of human influenza H5N1 virus isolates from Thailand. J. Gen Virol February 2005 vol. 86 no. 2 423-433 doi: 10.1099/vir.0.80368-0 http://vir.sgmjournals.org/content/86/2/423.long
93 Buranathai et al. 2007 Surveillance activities and molecular analysis of H5N1 highly pathogenic avian influenza viruses from Thailand, 2004-2005.Avian Diseases, Volume 51, issue s1 (March 2007), p. 194-200.DOI: 10.1637/7594-040306R.1 http://www.ncbi.nlm.nih.gov/pubmed/17494553 (Abstract)
92 Gabriel et al., 2008 Interaction of Polymerase Subunit PB2 and NP with Importin α1 Is a Determinant of Host Range of Influenza A Virus. PLoS Pathog 4(2): e11. doi:10.1371/journal.ppat.0040011 http://www.plospathogens.org/article...l.ppat.0040011
93 Jiao et al. 2008 A Single-Amino-Acid Substitution in the NS1 Protein Changes the Pathogenicity of H5N1 Avian Influenza Viruses in Mice. J Virol. 2008 February; 82(3): 1146–1154 doi: 10.1128/JVI.01698-07
94 Long et al. 2008 Virulence of H5N1 avian influenza virus enhanced by a 15-nucleotide deletion in the viral nonstructural gene. Virus Genes Volume 36, Number 3 (2008), 471-478, DOI: 10.1007/s11262-007-0187-8 http://www.ncbi.nlm.nih.gov/pubmed/18317917 (Abstract)
95 Seo et al. 2002 Lethal H5N1 influenza viruses escape host anti-viral cytokine responses.Nat Med. 2002 Sep;8(9):950-4. doi:10.1038/nm757 http://www.ncbi.nlm.nih.gov/pubmed/12195436 (abstract)
96 Kuo and Krug et al. 2009 Influenza A Virus Polymerase Is an Integral Component of the CPSF30-NS1A Protein Complex in Infected Cells. J. Virol. February 2009 vol. 83 no. 4 1611-1616 doi: 10.1128/JVI.01491-08
97 Spesock et al. 2011 The Virulence of 1997 H5N1 Influenza Viruses in the Mouse Model Is Increased by Correcting a Defect in Their NS1 Proteins. J. Virol. July 2011 vol. 85 no. 14 7048-7058 http://jvi.asm.org/content/85/14/7048.full.pdf+html
98 Imai et al. 2010 The HA and NS Genes of Human H5N1 Influenza A Virus Contribute to High Virulence in Ferrets. PLoS Pathog 6(9): e1001106. doi:10.1371/journal.ppat.1001106 http://www.plospathogens.org/article...l.ppat.1001106
99 Jackson et al. 2008 A new influenza virus virulence determinant: The NS1 protein four C-terminal residues modulate pathogenicity.PNAS March 18, 2008 vol. 105 no. 11 4381-4386 doi: 10.1073/pnas.0800482105 http://www.pnas.org/content/105/11/4381.full.pdf+html
for NA also see Amino acid substitutions in the NAs of variants in clinical samples or isolates causing reduced antiviral susceptibility www.isirv.org/avg