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Host adaptation and transmission of influenza A viruses in mammals

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Pages 1-10 | Received 23 Sep 2015, Accepted 02 Nov 2015, Published online: 25 Jan 2019

  • Tong S, Zhu X, Li Y et al.New world bats harbor diverse influenza a viruses. PLoS Pathog2013;9: e1003657.
  • World Health Organization. Influenza (seasonal).Fact sheet No. 211.Geneva: WHO, 2009.Available at http://www.who.int/mediacentre/factsheets/fs211/en/index.html (accessed 9 December 2013).
  • Taubenberger JK, Morens DM.1918 Influenza: the mother of all pandemics. Emerg Infect Dis2006;12: 15–22.
  • Scholtissek C, Rohde W, von Hoyningen V, Rott R.On the origin of the human influenza virus subtypes H2N2 and H3N2. Virology1978;87: 13–20.
  • Neumann G, Noda T, Kawaoka Y.Emergence and pandemic potential of swine-origin H1N1 influenza virus. Nature2009;459: 931–939.
  • Smith GJ, Bahl J, Vijaykrishna D et al.Dating the emergence of pandemic influenza viruses. Proc Natl Acad Sci USA2009;106: 11709–11712.
  • Qi L, Davis AS, Jagger BW et al.Analysis by single-gene reassortment demonstrates that the 1918 influenza virus is functionally compatible with a low-pathogenicity avian influenza virus in mice. J Virol2012;86: 9211–9220.
  • Kilbourne ED.Influenza pandemics of the 20th century. Emerg Infect Dis2006;12: 9–14.
  • Nakajima K, Desselberger U, Palese P.Recent human influenza A (H1N1) viruses are closely related genetically to strains isolated in 1950. Nature1978;274: 334–339.
  • Dawood FS, Jain S, Finelli L et al.Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med2009;360: 2605–2615.
  • Hancock K, Veguilla V, Lu X et al.Cross-reactive antibody responses to the 2009 pandemic H1N1 influenza virus. N Engl J Med2009;361: 1945–1952.
  • Garten RJ, Davis CT, Russell CA et al.Antigenic and genetic characteristics of swine-origin 2009 A(H1N1) influenza viruses circulating in humans. Science2009;325: 197–201.
  • World Health Organization. Influenza at the human–animal interface.Geneva: WHO, 2013.Available at http://www.who.int/influenza/human_animal_interface/Influenza_Summary_IRA_HA_interface_7October13.pdf (accessed 7 October 2013).
  • Imai M, Watanabe T, Hatta M et al.Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets. Nature2012;486: 420–428.
  • Herfst S, Schrauwen EJ, Linster M et al.Airborne transmission of influenza A/H5N1 virus between ferrets. Science2012;336: 1534–1541.
  • Zhang Y, Zhang Q, Kong H et al.H5N1 hybrid viruses bearing 2009/H1N1 virus genes transmit in guinea pigs by respiratory droplet. Science2013;340: 1459–1463.
  • Ostrowsky B, Huang A, Terry W et al.Low pathogenic avian influenza A (H7N2) virus infection in immunocompromised adult, New York, USA, 2003. Emerg Infect Dis2012;18: 1128–1131.
  • Tweed SA, Skowronski DM, David ST et al.Human illness from avian influenza H7N3, British Columbia. Emerg Infect Dis2004;10: 2196–2199.
  • Fouchier RA, Schneeberger PM, Rozendaal FW et al.Avian influenza A virus (H7N7) associated with human conjunctivitis and a fatal case of acute respiratory distress syndrome. Proc Natl Acad Sci USA2004;101: 1356–1361.
  • Gao R, Cao B, Hu Y et al.Human infection with a novel avian-origin influenza A (H7N9) virus. N Engl J Med2013;368: 1888–1897.
  • Centers for Disease Prevention.Notes from the field: Highly pathogenic avian influenza A (H7N3) virus infection in two poultry workers—Jalisco, Mexico, July 2012. MMWR Morb Mortal Wkly Rep2012;61: 726–727.
  • Richard M, Schrauwen EJ, de Graaf M et al.Limited airborne transmission of H7N9 influenza A virus between ferrets. Nature2013;501: 560–563.
  • Zhu H, Wang D, Kelvin DJ et al.Infectivity, transmission, and pathology of human H7N9 influenza in ferrets and pigs. Science2013;341: 183–186.
  • Watanabe T, Kiso M, Fukuyama S et al.Characterization of H7N9 influenza A viruses isolated from humans. Nature2013;501: 551–555.
  • Belser JA, Gustin KM, Pearce MB et al.Pathogenesis and transmission of avian influenza A (H7N9) virus in ferrets and mice. Nature2013;501: 556–559.
  • Butt KM, Smith GJ, Chen H et al.Human infection with an avian H9N2 influenza A virus in Hong Kong in 2003. J Clin Microbiol2005;43: 5760–5767.
  • Peiris M, Yuen KY, Leung CW et al.Human infection with influenza H9N2. Lancet1999;354: 916–917.
  • Cheng VC, Chan JF, Wen X et al.Infection of immunocompromised patients by avian H9N2 influenza A virus. J Infect2011;62: 394–399.
  • Sorrell EM, Wan H, Araya Y, Song H, Perez DR.Minimal molecular constraints for respiratory droplet transmission of an avian-human H9N2 influenza A virus. Proc Natl Acad Sci USA2009;106: 7565–7570.
  • Yuan J, Zhang L, Kan X et al.Origin and molecular characteristics of a novel 2013 avian influenza A H6N1 virus causing human infection in Taiwan. Clin Infect Dis2013;57: 1367–1368.
  • Arzey GG, Kirkland PD, Arzey KE et al.Influenza virus A (H10N7) in chickens and poultry abattoir workers, Australia. Emerg Infect Dis2012;18: 814–816.
  • Centers for Disease Control and Prevention. Reported infections with variant influenza viruses in the United States since 2005.Atlanta, GA: CDC, 2013.Available at http://www.cdc.gov/flu/swineflu/variant-cases-us.htm (accessed 5 November 2013).
  • Pearce MB, Jayaraman A, Pappas C et al.Pathogenesis and transmission of swine origin A(H3N2)v influenza viruses in ferrets. Proc Natl Acad Sci USA2012;109: 3944–3949.
  • Pascua PN, Song MS, Lee JH et al.Virulence and transmissibility of H1N2 influenza virus in ferrets imply the continuing threat of triple-reassortant swine viruses. Proc Natl Acad Sci USA2012;109: 15900–15905.
  • Hatchette TF, Walker D, Johnson C, Baker A, Pryor SP, Webster RG.Influenza A viruses in feral Canadian ducks: extensive reassortment in nature. J Gen Virol2004;85(Pt 8): 2327–2337.
  • de Jong JC, Claas EC, Osterhaus AD, Webster RG, Lim WL.A pandemic warning? Nature1997;389: 554.
  • Kandun IN, Wibisono H, Sedyaningsih ER et al.Three Indonesian clusters of H5N1 virus infection in 2005. N Engl J Med2006;355: 2186–2194.
  • Wang H, Feng Z, Shu Y et al.Probable limited person-to-person transmission of highly pathogenic avian influenza A (H5N1) virus in China. Lancet2008;371: 1427–1434.
  • Ungchusak K, Auewarakul P, Dowell SF et al.Probable person-to-person transmission of avian influenza A (H5N1). N Engl J Med2005;352: 333–340.
  • Lam TT, Wang J, Shen Y et al.The genesis and source of the H7N9 influenza viruses causing human infections in China. Nature2013;502: 241–244.
  • Qi X, Qian YH, Bao CJ et al.Probable person to person transmission of novel avian influenza A (H7N9) virus in Eastern China, 2013: epidemiological investigation. BMJ2013;347: f4752.
  • de Wit E, Fouchier RA.Emerging influenza. J Clin Virol2008;41: 1–6.
  • Liu D, Shi W, Shi Y et al.Origin and diversity of novel avian influenza A H7N9 viruses causing human infection: phylogenetic, structural, and coalescent analyses. Lancet2013;381: 1926–1932.
  • Matrosovich MN, Krauss S, Webster RG.H9N2 influenza A viruses from poultry in Asia have human virus-like receptor specificity. Virology2001;281: 156–162.
  • Gillim-Ross L, Santos C, Chen Z et al.Avian influenza h6 viruses productively infect and cause illness in mice and ferrets. J Virol2008;82: 10854–10863.
  • Munster VJ, Baas C, Lexmond P et al.Spatial, temporal, and species variation in prevalence of influenza A viruses in wild migratory birds. PLoS Pathog2007;3: e61.
  • Krauss S, Obert CA, Franks J et al.Influenza in migratory birds and evidence of limited intercontinental virus exchange. PLoS Pathog2007;3: e167.
  • Ma W, Vincent AL, Gramer MR et al.Identification of H2N3 influenza A viruses from swine in the United States. Proc Natl Acad Sci USA2007;104: 20949–20954.
  • Centers for Disease Control and Prevention. H1N2 variant virus detected in Minnesota. Atlanta, GA: CDC, 2012.Available at http://www.cdc.gov/flu/spotlights/h1n2v-cases-mn.htm (accessed 7 September 2012).
  • Nelson MI, Vincent AL, Kitikoon P, Holmes EC, Gramer MR.Evolution of novel reassortant A/H3N2 influenza viruses in North American swine and humans, 2009–2011. J Virol2012;86: 8872–8878.
  • Shu B, Garten R, Emery S et al.Genetic analysis and antigenic characterization of swine origin influenza viruses isolated from humans in the United States, 1990–2010. Virology2012;422: 151–160.
  • Hatta M, Gao P, Halfmann P, Kawaoka Y.Molecular basis for high virulence of Hong Kong H5N1 influenza A viruses. Science2001;293: 1840–1842.
  • Rimmelzwaan GF, Kuiken T, van Amerongen G, Bestebroer TM, Fouchier RA, Osterhaus AD.Pathogenesis of influenza A (H5N1) virus infection in a primate model. J Virol2001;75: 6687–6691.
  • Schrauwen EJ, Herfst S, Leijten LM et al.The multibasic cleavage site in H5N1 virus is critical for systemic spread along the olfactory and hematogenous routes in ferrets. J Virol2012;86: 3975–3984.
  • Suguitan AL Jr, Matsuoka Y, Lau YF et al.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 Virol2012;86: 2706–2714.
  • Schrauwen EJ, Bestebroer TM, Munster VJ et al.Insertion of a multibasic cleavage site in the haemagglutinin of human influenza H3N2 virus does not increase pathogenicity in ferrets. J Gen Virol2011;92(Pt 6): 1410–1415.
  • Kilander A, Rykkvin R, Dudman SG, Hungnes O.Observed association between the HA1 mutation D222G in the 2009 pandemic influenza A(H1N1) virus and severe clinical outcome, Norway 2009–2010. Euro Surveill2010;15: 19498.
  • Chutinimitkul S, Herfst S, Steel J et al.Virulence-associated substitution D222G in the hemagglutinin of 2009 pandemic influenza A(H1N1) virus affects receptor binding. J Virol2010 Nov;84: 11802–11813.
  • Chutinimitkul S, van Riel D, Munster VJ et al.In vitro assessment of attachment pattern and replication efficiency of H5N1 influenza A viruses with altered receptor specificity. J Virol2010;84: 6825–6833.
  • Yamada S, Suzuki Y, Suzuki T et al.Haemagglutinin mutations responsible for the binding of H5N1 influenza A viruses to human-type receptors. Nature2006;444: 378–382.
  • Watanabe Y, Ibrahim MS, Ellakany HF et al.Acquisition of human-type receptor binding specificity by new H5N1 influenza virus sublineages during their emergence in birds in Egypt. PLoS Pathog2011;7: e1002068.
  • van Riel D, Leijten LM, de Graaf M et al.Novel avian-origin influenza A (H7N9) virus attaches to epithelium in both upper and lower respiratory tract of humans. Am J Pathol2013;183: 1137–1143.
  • Shinya K, Ebina M, Yamada S, Ono M, Kasai N, Kawaoka Y.Avian flu: influenza virus receptors in the human airway. Nature2006;440: 435–436.
  • Sun X, Jayaraman A, Maniprasad P et al.N-linked glycosylation of the hemagglutinin protein influences virulence and antigenicity of the 1918 pandemic and seasonal H1N1 influenza A viruses. J Virol2013;87: 8756–8766.
  • Zhang Y, Zhu J, Li Y et al.Glycosylation on hemagglutinin affects the virulence and pathogenicity of pandemic H1N1/2009 influenza A virus in mice. PLoS ONE2013;8: e61397.
  • Wang W, Lu B, Zhou H et al.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 Virol2010;84: 6570–6577.
  • Chen H, Bright RA, Subbarao K et al.Polygenic virulence factors involved in pathogenesis of 1997 Hong Kong H5N1 influenza viruses in mice. Virus Res2007;128: 159–163.
  • Wagner R, Matrosovich M, Klenk HD.Functional balance between haemagglutinin and neuraminidase in influenza virus infections. Rev Med Virol2002;12: 159–166.
  • de Wit E, Munster VJ, van Riel D et al.Molecular determinants of adaptation of highly pathogenic avian influenza H7N7 viruses to efficient replication in the human host. J Virol2010;84: 1597–1606.
  • Munier S, Larcher T, Cormier-Aline F et al.A genetically engineered waterfowl influenza virus with a deletion in the stalk of the neuraminidase has increased virulence for chickens. J Virol2010;84: 940–952.
  • Matsuoka Y, Swayne DE, Thomas C et al.Neuraminidase stalk length and additional glycosylation of the hemagglutinin influence the virulence of influenza H5N1 viruses for mice. J Virol2009;83: 4704–4708.
  • Gabriel G, Klingel K, Otte A et al.Differential use of importin-alpha isoforms governs cell tropism and host adaptation of influenza virus. Nat Commun2011;2: 156.
  • Mehle A, Doudna JA.Adaptive strategies of the influenza virus polymerase for replication in humans. Proc Natl Acad Sci USA2009;106: 21312–21316.
  • Subbarao EK, London W, Murphy BR.A single amino acid in the PB2 gene of influenza A virus is a determinant of host range. J Virol1993;67: 1761–1764.
  • Steel J, Lowen AC, Mubareka S, Palese P.Transmission of influenza virus in a mammalian host is increased by PB2 amino acids 627K or 627E/701N. PLoS Pathog2009;5: e1000252.
  • Li Z, Chen H, Jiao P et al.Molecular basis of replication of duck H5N1 influenza viruses in a mammalian mouse model. J Virol2005;79: 12058–12064.
  • Gabriel G, Herwig A, Klenk HD.Interaction of polymerase subunit PB2 and NP with importin alpha1 is a determinant of host range of influenza A virus. PLoS Pathog2008;4: e11.
  • Le QM, Ito M, Muramoto Y et al.Pathogenicity of highly pathogenic avian H5N1 influenza A viruses isolated from humans between 2003 and 2008 in northern Vietnam. J Gen Virol2010;91(Pt 10): 2485–2490.
  • Herfst S, Chutinimitkul S, Ye J et al.Introduction of virulence markers in PB2 of pandemic swine-origin influenza virus does not result in enhanced virulence or transmission. J Virol2010;84: 3752–3758.
  • Manz B, Schwemmle M, Brunotte L.Adaptation of avian influenza a virus polymerase in mammals to overcome the host species barrier. J Virol2013;87: 7200–7209.
  • Conenello GM, Zamarin D, Perrone LA, Tumpey T, Palese P.A single mutation in the PB1-F2 of H5N1 (HK/97) and 1918 influenza A viruses contributes to increased virulence. PLoS Pathog2007;3: 1414–1421.
  • Varga ZT, Ramos I, Hai R et al.The influenza virus protein PB1-F2 inhibits the induction of type I interferon at the level of the MAVS adaptor protein. PLoS Pathog2011;7: e1002067.
  • McAuley JL, Chipuk JE, Boyd KL, van de Velde N, Green DR, McCullers JA.PB1-F2 proteins from H5N1 and 20 century pandemic influenza viruses cause immunopathology. PLoS Pathog2010;6: e1001014.
  • Hai R, Schmolke M, Varga ZT et al.PB1-F2 expression by the 2009 pandemic H1N1 influenza virus has minimal impact on virulence in animal models. J Virol2010;84: 4442–4450.
  • McAuley JL, Hornung F, Boyd KL et al.Expression of the 1918 influenza A virus PB1-F2 enhances the pathogenesis of viral and secondary bacterial pneumonia. Cell Host Microbe2007;2: 240–249.
  • Jagger BW, Wise HM, Kash JC et al.An overlapping protein-coding region in influenza A virus segment 3 modulates the host response. Science2012;337: 199–204.
  • Shi M, Jagger BW, Wise HM, Digard P, Holmes EC, Taubenberger JK.Evolutionary conservation of the PA-X open reading frame in segment 3 of influenza A virus. J Virol2012;86: 12411–12413.
  • Garcia-Sastre A.Induction and evasion of type I interferon responses by influenza viruses. Virus Res2011;162: 12–18.
  • Garcia-Sastre A, Egorov A, Matassov D et al.Influenza A virus lacking the NS1 gene replicates in interferon-deficient systems. Virology1998;252: 324–330.
  • Peiris JS, Yu WC, Leung CW et al.Re-emergence of fatal human influenza A subtype H5N1 disease. Lancet2004;363: 617–619.
  • Seo SH, Hoffmann E, Webster RG.Lethal H5N1 influenza viruses escape host anti-viral cytokine responses. Nat Med2002;8: 950–954.
  • Obenauer JC, Denson J, Mehta PK et al.Large-scale sequence analysis of avian influenza isolates. Science2006;311: 1576–1580.
  • Jackson D, Hossain MJ, Hickman D, Perez DR, Lamb RA.A new influenza virus virulence determinant: the NS1 protein four C-terminal residues modulate pathogenicity. Proc Natl Acad Sci USA2008;105: 4381–4386.
  • Twu KY, Kuo RL, Marklund J, Krug RM.The H5N1 influenza virus NS genes selected after 1998 enhance virus replication in mammalian cells. J Virol2007;81: 8112–8121.
  • Hale BG, Steel J, Medina RA et al.Inefficient control of host gene expression by the 2009 pandemic H1N1 influenza A virus NS1 protein. J Virol2010;84: 6909–6922.
  • Finkelstein DB, Mukatira S, Mehta PK et al.Persistent host markers in pandemic and H5N1 influenza viruses. J Virol2007;81: 10292–10299.
  • Chen LM, Blixt O, Stevens J et al.In vitro evolution of H5N1 avian influenza virus toward human-type receptor specificity. Virology2012;422: 105–113.
  • Matrosovich M, Tuzikov A, Bovin N et al.Early alterations of the receptor-binding properties of H1, H2, and H3 avian influenza virus hemagglutinins after their introduction into mammals. J Virol2000;74: 8502–8512.
  • Pappas C, Viswanathan K, Chandrasekaran A et al.Receptor specificity and transmission of H2N2 subtype viruses isolated from the pandemic of 1957. PLoS ONE2010;5: e11158.doi: https://doi.org/10.1371/journal.pone.0011158.
  • Tumpey TM, Maines TR, van Hoeven N et al.A two-amino acid change in the hemagglutinin of the 1918 influenza virus abolishes transmission. Science2007;315: 655–659.
  • Maines TR, Chen LM, van Hoeven N et al.Effect of receptor binding domain mutations on receptor binding and transmissibility of avian influenza H5N1 viruses. Virology2011;413: 139–147.
  • Zhang W, Shi Y, Lu X, Shu Y, Qi J, Gao GF.An airborne transmissible avian influenza H5 hemagglutinin seen at the atomic level. Science2013;340: 1463–1467.
  • Lu X, Shi Y, Zhang W, Zhang Y, Qi J, Gao GF.Structure and receptor-binding properties of an airborne transmissible avian influenza A virus hemagglutinin H5 (VN1203mut). Protein Cell2013;4: 502–511.
  • Xiong X, Coombs PJ, Martin SR et al.Receptor binding by a ferret-transmissible H5 avian influenza virus. Nature2013;497: 392–396.
  • Rudneva IA, Ilyushina NA, Timofeeva TA, Webster RG, Kaverin NV.Restoration of virulence of escape mutants of H5 and H9 influenza viruses by their readaptation to mice. J Gen Virol2005;86(Pt 10): 2831–2838.
  • Gao Y, Zhang Y, Shinya K et al.Identification of amino acids in HA and PB2 critical for the transmission of H5N1 avian influenza viruses in a mammalian host. PLoS Pathog2009;5: e1000709.
  • Neumann G, Macken CA, Karasin AI, Fouchier RA, Kawaoka Y.Egyptian H5N1 influenza viruses-cause for concern? PLoS Pathog2012;8: e1002932.
  • Zhang Q, Shi J, Deng G et al.H7N9 influenza viruses are transmissible in ferrets by respiratory droplet. Science2013;341: 410–414.
  • Belser JA, Maines TR, Katz JM, Tumpey TM.Considerations regarding appropriate sample size for conducting ferret transmission experiments. Future Microbiol2013;8: 961–965.
  • Ruigrok RW, Martin SR, Wharton SA, Skehel JJ, Bayley PM, Wiley DC.Conformational changes in the hemagglutinin of influenza virus which accompany heat-induced fusion of virus with liposomes. Virology1986;155: 484–497.
  • Zaraket H, Bridges OA, Russell CJ.The pH of activation of the hemagglutinin protein regulates H5N1 influenza virus replication and pathogenesis in mice. J Virol2013;87: 4826–4834.
  • Zaraket H, Bridges OA, Duan S et al.Increased acid stability of the hemagglutinin protein enhances H5N1 influenza virus growth in the upper respiratory tract but is insufficient for transmission in ferrets. J Virol2013;87: 9911–9922.
  • Lowen AC, Steel J, Mubareka S, Carnero E, Garcia-Sastre A, Palese P.Blocking interhost transmission of influenza virus by vaccination in the guinea pig model. J Virol2009;83: 2803–2818.
  • Munster VJ, de Wit E, van den Brand JM et al.Pathogenesis and transmission of swine-origin 2009 A(H1N1) influenza virus in ferrets. Science2009;325: 481–483.
  • Zhou B, Pearce MB, Li Y et al.Asparagine substitution at PB2 residue 701 enhances the replication, pathogenicity, and transmission of the 2009 pandemic H1N1 influenza A virus. PLoS ONE2013;8: e67616.
  • Schrauwen EJ, Bestebroer TM, Rimmelzwaan GF, Osterhaus AD, Fouchier RA, Herfst S.Reassortment between Avian H5N1 and human influenza viruses is mainly restricted to the matrix and neuraminidase gene segments. PLoS ONE2013;8: e59889.
  • Jackson S, van Hoeven N, Chen LM et al.Reassortment between avian H5N1 and human H3N2 influenza viruses in ferrets: a public health risk assessment. J Virol2009;83: 8131–8140.
  • Maines TR, Chen LM, Matsuoka Y et al.Lack of transmission of H5N1 avian-human reassortant influenza viruses in a ferret model. Proc Natl Acad Sci USA2006;103: 12121–12126.
  • Lakdawala SS, Lamirande EW, Suguitan AL Jr et al.Eurasian-origin gene segments contribute to the transmissibility, aerosol release, and morphology of the 2009 pandemic H1N1 influenza virus. PLoS Pathog2011;7: e1002443.
  • Pascua PN, Song MS, Kwon HI et al.The homologous tripartite viral RNA polymerase of A/swine/Korea/CT1204/2009(H1N2) influenza virus synergistically drives efficient replication and promotes respiratory-droplet transmission in ferrets. J Virol2013;87: 10552–10562.
  • Blumenkrantz D, Roberts KL, Shelton H, Lycett S, Barclay WS.The short stalk length of highly pathogenic avian influenza H5N1 virus neuraminidase limits transmission of pandemic H1N1 virus in ferrets. J Virol2013;87: 10539–10551.
  • Kilbourne ED, Murphy JS.Genetic studies of influenza viruses. I. Viral morphology and growth capacity as exchangeable genetic traits. Rapid in ovo adaptation of early passage Asian strain isolates by combination with PR8. J Exp Med1960;111: 387–406.
  • Sorrell E, Schrauwen E, Linster M, de Graaf M, Herfst S, Fouchier R.Predicting ‘airborne’ influenza viruses: (trans-) mission impossible? Curr Opin Virol2011;1: 635–642.