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Insight into Influenza Viruses of Animals and Humans pp 115–131Cite as

Pathogenesis and Pathogenicity of Influenza Viruses

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Abstract

Influenza viruses can produce a wide variety of pathological lesions in different organs of poultry and mammals. Based on morphological, cellular and biochemical evidences in various animal models, the virus exerts pathological effect by two mechanisms, viz. necrosis and apoptosis. The tissue tropism of the influenza virus and tissue specific expression of virus receptors appears to play a pivotal role in pathogenesis. The mortality may be due to systemic viral spread, cytokine storm, or alveolar flooding due to inhibition of cellular sodium channels. The levels and functional potential of alveolar macrophages, various cytokines have a role in the influenza virus-induced pathology. Although all gene product of influenza virus contribute to pathogenicity, however, haemagglutinin plays a key role. The structure of the HA cleavage site is different in low pathogenic avian influenza viruses (LPAI) and highly pathogenic avian influenza viruses (HPAI). Also, the location of host proteases causing cleavage of these two type of the HA is different. The other important virulence determinant is the presence of a carbohydrate side chain nearby the cleavage site that interferes with the protease accessibility. The emergence of H5N1 in 1997, H1N1pdm in 2009 and now H7N9 influenza A viruses in 2013 provide lot of lessons to be learnt by understanding their pathogenesis and pathogenicity. Pathogenicity and transmissibility play a central role in the possibility and probability of a viral strain to emerge as a new influenza subtype in humans and act as a potentially pandemic influenza virus.

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References

  • Abed Y, Pizzorno A, Hamelin ME et al (2011) The 2009 pandemic H1N1 D222G hemagglutinin mutation alters receptor specificity and increases virulence in mice but not in ferrets. J Infect Dis 204:1008–1016

    Google Scholar 

  • Alexander DJ (2001) Orthomyxoviridae—avian influenza. In: Jordan F, Pattison M, Alexander D, Faragher T (eds) Poultry diseases, 5th Edn. W.B. Saunders, London, p 272–279

    Google Scholar 

  • Almond JW (1977) A single gene determines the host range of influenza virus. Nature 270:617–618

    Article  PubMed  CAS  Google Scholar 

  • Arankalle VA, Lole KS, Arya RP et al (2009) Role of host immune response and viral load in the differential outcome of pandemic H1N1 influenza virus infection in Indian patients. PLoS ONE 5:e13099

    Article  CAS  Google Scholar 

  • Barnard DL (2009) Animal models for the study of influenza pathogenesis and therapy. Antiviral Res 82:A110–A122

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Belser JA, Gustin KM, Pearce MB et al (2013a) Pathogenesis and transmission of avian influenza A (H7N9) virus in ferrets and mice. Nature doi:10.1038/nature12391 Published online10 July 2013

  • Belser JA, Davis CT, Balish A et al (2013b) Pathogenesis, transmissibility, and ocular tropism of a highly pathogenic avian influenza A (H7N3) virus associated with human conjunctivitis. J Virol 87(10):5746–5754

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Belser JA, Jayaraman A, Raman R et al (2011) Effect of D222G mutation in the hemagglutinin protein on receptor binding, pathogenesis and transmissibility of the 2009 pandemic H1N1 influenza virus. PLoS ONE 6:e25091

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Belser JA, Tumpey TM (2013) Tropism of H7N9 influenza viruses in the human respiratory tract. Lancet Respir Med 1(7):501–502. doi:10.1016/S2213-2600(13)70161

    Article  PubMed  Google Scholar 

  • Betts RJ, Mann TS, Henry PJ (2012) Inhibitory influence of the hexapeptidic sequence SLIGRL on influenza A virus infection in mice. J Pharmacol Exp Ther 343:725–735

    Article  PubMed  CAS  Google Scholar 

  • Boivin S, Hart DJ (2011) Interaction of the influenza A virus polymerase PB2 C-terminal region with importin alpha isoforms provides insights into host adaptation and polymerase assembly. J Biol Chem 286:10439–10448

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Bortz E, Westera L, Maamary J et al (2011) Host- and strain-specific regulation of influenza virus polymerase activity by interacting cellular proteins. MBio 2, doi:10.1128/mBio.00151-11

  • Bosch FX, Garten W, Klenk HD et al (1981) Proteolytic cleavage of influenza virus haemagglutinins: Primary structure of the connecting peptide between HA1 and HA2 determines proteolytic cleavability and pathogenicity of avian influenza viruses. Virology 113:725–735

    Article  PubMed  CAS  Google Scholar 

  • Bosch FX, Orlich M, Klenk HD et al (1979) The structure of the haemagglutinin, a determinant for pathogenicity of influenza viruses. Virology 95:197–207

    Article  PubMed  CAS  Google Scholar 

  • Camp JV, Chu YK, Chung DH et al (2013) Phenotypic differences in virulence and immune response in closely related clinical isolates of influenza A 2009 H1N1 pandemic viruses in mice. PLoS ONE 44:e56602. doi:10.1371/journal.pone.0056602

    Article  CAS  Google Scholar 

  • Chang SY, Lin PH, Tsai JC et al (2013) The first case of H7N9 influenza in Taiwan. Lancet 381:1621

    Article  PubMed  Google Scholar 

  • Cheung CY, Poon LL, Lau AS et al (2002) Induction of proinflamatory cytokines in human macrophages by influenza A (H5N1) viruses: a mechanism for the unusual severity of human disease? Lancet 360:1831–1837

    Article  PubMed  CAS  Google Scholar 

  • Chi Y, Zhu Y, Wen T et al (2013) Cytokine and chemokine levels in patients infected with the novel avian influenza A (H7N9) virus in China. J Infect Dis. doi: 10.1093/infdis/jit440

  • Chutinimitkul S, Herfst S, Steel J et al (2010) Virulence-associated substitution D222G in the hemagglutinin of 2009 pandemic influenza A(H1N1) virus affects receptor binding. J Virol 84:11802–11813

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Council of European Communities (1992) Council Directive of 19 May 1992 Introducing Community measures for the control of avian influenza 92/40/EC (OJ L 167, 22.06.92, p 1 amended by Accession Treaty of 1994). http://ec.europa.eu/food/animal/diseases/resources/92-40_en.pdf

  • Crescenzo-Chaigne B, van der Werf S, Naffakh N (2002) Differential effect of nucleotide substitutions in the 3’ arm of influenza A virus vRNA promoter on transcription/replication by avian and human polymerase complexes is related to the nature of PB2 amino acid 627. Virology 303:240–252

    Article  PubMed  CAS  Google Scholar 

  • Dawood FS, Jain S, Finelli L et al (2009) Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med 44:2605–2615

    Google Scholar 

  • de Wit E, Fouchier RA (2008) Emerging influenza. J Clin Virol 41:1–6

    Article  PubMed Central  PubMed  Google Scholar 

  • Deshpande KL, Fried VL, Ando M et al (1987) Glycosylation affects cleavage of an H5N2 influenza virus haemagglutinin and regulates virulence. Proc Natl Acad Sci USA 84:36–40

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Earnshaw WC, Martins LM, Kaufmann SH (1999) Mammalian caspases: structure, activation, substrates, and functions during apoptosis. Annu Rev Biochem 68:383–424

    Article  PubMed  CAS  Google Scholar 

  • ECDC (2013) Diagnostic preparedness in Europe for detection of avian influenza A(H7N9) viruses.(http://www.ecdc.europa.eu/en/publications/Publications/Forms/ECDC_DispForm.aspx?ID=1103)

  • Farooqui A, Leon AJ, Lei Y et al (2012) Heterogeneous virulence of pandemic 2009 influenza H1N1 virus in mice. Virol J 44:104. doi:10.1186/1743-422X-9-104

    Article  Google Scholar 

  • Fouchier RA, Schneeberger PM, Rozendaal FW et al (2004) Avian influenza A virus (H7N7) associated with human conjunctivitis and a fatal case of acute respiratory distress syndrome. Proc Natl Acad Sci USA 101:1356–1361

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Frankova V (1975) Inhalatory infection of mice with influenza Ao/PR8 virus. I. The site of primary virus replication and its spread in the respiratory tract. Acta Virol 19:29–34

    PubMed  CAS  Google Scholar 

  • Friesenhagen J, Boergeling Y, Hrincius E et al (2012) Highly pathogenic avian influenza viruses inhibit effective immune responses of human blood-derived macrophages. J Leukoc Biol 92(1):11–20

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Gabriel G, Dauber B, Wolff T et al (2005) The viral polymerase mediates adaptation of an avian influenza virus to a mammalian host. Proc Natl Acad Sci USA 102:18590–18595

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Gao R, Cao B, Hu Y et al (2013) Human infection with a novel avian-origin influenza A (H7N9) Virus. New Engl J Med 368(20):1888–1889

    Article  PubMed  CAS  Google Scholar 

  • Gao P, Watanabe S, Ito T et al (1999) Biological heterogeneity, including systemic replication in mice, of H5N1 influenza A virus isolates from humans in Hong Kong. J Virol 73:3184–3189

    PubMed Central  PubMed  CAS  Google Scholar 

  • García-Sastre A, Tscherne DM (2011) Virulence determinants of pandemic influenza viruses. J Clin Invest 121(1):6–13. doi:10.1172/JCI44947

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Garten W, Bosch FX, Linder D et al (1981) Proteolytic activation of the influenza virus haemagglutinin: The structure of the cleavage site and the enzymes involved in cleavage. Virology 115:361–374

    Article  PubMed  CAS  Google Scholar 

  • Giesendorf B, Bosch FX, Orlich M et al (1986) Studies on the temperature sensitivity of influenza A virus reassortants non-pathogenic for chicken. Virus Res 5:27–42

    Article  PubMed  CAS  Google Scholar 

  • Goto H, Kawaoka Y (1998) A novel mechanism for the acquisition of virulence by a human influenza A virus. Proc Natl Acad Sci USA 95:10224–10228

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Hatta M, Gao P, Halfmann P et al (2001) Molecular basis for high virulence of Hong Kong H5N1 influenza A viruses. Science 293:1840–1842

    Article  PubMed  CAS  Google Scholar 

  • Herfst S, Chutinimitkul S, Ye J et al (2010) Introduction of virulence markers in PB2 of pandemic swine-origin influenza virus does not result in enhanced virulence or transmission. J Virol 84:3752–3758

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Heui SS, Hoffmann E, Webster RG (2002) Lethal H5N1 influenza viruses escape host anti-viral cytokine responses. Nat Med 8:950–954

    Article  CAS  Google Scholar 

  • Hinshaw VS, Olsen CW, Dybdahl-Sissoko N et al (1994) Apoptosis: a mechanism of cell killing by influenza A and B viruses. J Virol 68:3667–3673

    PubMed Central  PubMed  CAS  Google Scholar 

  • Horimoto T, Kawaoka Y (1994) Reverse genetics provides direct evidence for a correlation of haemagglutinin cleavability and virulence of an avian influenza virus. J Virol 68:3120–3128

    PubMed Central  PubMed  CAS  Google Scholar 

  • Hu Y, Lu S, Song Z et al (2013) Association between adverse clinical outcome in human disease caused by novel influenza A H7N9 virus and sustained viral shedding and emergence of antiviral resistance. The Lancet. doi:10.1016/S0140-6736(13)61125-3

    PubMed  Google Scholar 

  • Hulse DJ, Webster RG, Russell RJ et al (2004) Molecular determinants within the surface proteins involved in the pathogenicity of H5N1 influenza viruses in chickens. J Virol 78:9954–9964

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Ito T, Kobayashi Y, Morita T et al (2002) Virulent influenza A viruses induce apoptosis in chickens. Virus Res 84:27–35

    Article  PubMed  CAS  Google Scholar 

  • Jackson D, Hossain MJ, Hickman D et al (2008) A new influenza virus virulence determinant: The NS1 protein four C-terminal residues modulate pathogenicity. Proc Natl Acad Sci USA 105:4381–4386

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Jiao P, Tian G, Li Y et al (2008) A single-amino-acid substitution in the NS1 protein changes the pathogenicity of H5N1 avian influenza viruses in mice. J Virol 82:1146–1154

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Julkunen I, Sareneva T, Pirhonen J et al (2001) Molecular pathogenesis of influenza A virus infection and virus-induced regulation of cytokine gene expression. Cytokine Growth Factor Rev 12(2–3):171–180

    Article  PubMed  CAS  Google Scholar 

  • Kageyama T, Fujisaki S, Takashita E et al (2013) Genetic analysis of novel avian A (H7N9) influenza viruses isolated from patients in China, February to April 2013. Euro Surveill 18(15):20453

    PubMed  CAS  Google Scholar 

  • Kajihara M, Sakoda Y, Soda K et al (2013) The PB2, PA, HA, NP, and NS genes of a highly pathogenic avian influenza virus A/whooper swan/Mongolia/3/2005 (H5N1) are responsible for pathogenicity in ducks. Virol J 10:45. doi:10.1186/1743-422X-10-45

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Katz JM, Lu X, Tumpey TM et al (2000) Molecular correlates of influenza A H5N1 virus pathogenesis in mice. J Virol 74:10807–10810

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Kawaoka Y, Webster RG (1988) Sequence requirements for cleavage activation of influenza virus haemagglutinin expressed in mammalian cells. Proc Natl Acad Sci USA 85:321–328

    Article  Google Scholar 

  • Kawaoka Y, Naeve CW, Webster RG (1984) Is virulence of H5N2 influenza viruses in chickens associated with loss of carbohydrate from the haemagglutinin? Virology 139:303–316

    Article  PubMed  CAS  Google Scholar 

  • Klenk HD (2005) Infection of the endothelium by influenza viruses. Thromb Haemost 94:262–265

    PubMed  CAS  Google Scholar 

  • Klenk HD, Rott R (1980) Cotranslational and post-translational processing of viral glycoproteins. Curr Top Microbiol Immunol 90:19–48

    PubMed  CAS  Google Scholar 

  • Klenk HD, Rott R (1988) The molecular biology of influenza virus pathogenicity. Adv Virus Res 34:247–281

    Google Scholar 

  • Klenk HD, Rott R, Orlich M et al (1975) Activation of influenza A viruses by trpsin treatment. Virology 68:426–439

    Article  PubMed  CAS  Google Scholar 

  • Korteweg C, Gu J (2008) Pathology, molecular biology, and pathogenesis of avian influenza A (H5N1) infection in humans. Am J Pathol 172:1155–1170

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Kuiken T, Riteau B, Fouchier RAM et al (2012) Pathogenesis of influenzavirus infections: the good, the bad and the ugly. Curr Opin Virol 2(3):276–286

    Article  PubMed  CAS  Google Scholar 

  • Lam WY, Tang JW, Yeung ACM et al (2008) Avian influenza virus A/HK/483/97(H5N1) NS1 protein induces apoptosis in human airway epithelial cells. J Virol 82:2741–2751

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Lamb RA (2013) Deadly H7N9 influenza virus: a pandemic in the making or a warning lesson?”. Am J Respir Crit Care Med 188(1):1–2

    Article  PubMed  Google Scholar 

  • Li Y, Zou W, Jia G et al (2013) The 2009 pandemic (H1N1) viruses isolated from pigs show enhanced pathogenicity in mice. Vet Res 44(1):41. doi:10.1186/1297-9716-44-41

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Li KS, Guan Y, Wang J et al (2004) Genesis of a highly pathogenic and potentially pandemic H5N1 influenza virus in eastern Asia. Nature 430:209–213

    Article  PubMed  CAS  Google Scholar 

  • Li S, Orlich M, Rott R (1990) Generation of seal influenza virus variants pathogenic for chickens because of haemagglutinin cleavage sites. J Virol 64:3297–3303

    PubMed Central  PubMed  CAS  Google Scholar 

  • Lin TY, Brass AL (2013) Host genetic determinants of influenza pathogenicity. Curr Opin Virol 3(5):531–536

    Article  PubMed  CAS  Google Scholar 

  • Ling MT, Tu W, Han Y et al (2012) Mannose-binding lectin contributes to deleterious inflammatory response in pandemic H1N1 and avian H9N2 infection. J Infect Dis 205(1):44–53. doi:10.1093/infdis/jir691

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Lipatov AS, Andreansky S, Webby RJ et al (2005) Pathogenesis of Hong Kong H5N1 influenza virus NS gene reassortants in mice: the role of cytokines and B- and T-cell responses. J Gen Virol 86:1121–1130

    Article  PubMed  CAS  Google Scholar 

  • Lipatov AS, Krauss S, Guan Y et al (2003) Neurovirulence in mice of H5N1 influenza virus genotypes isolated from Hong Kong poultry in 2001. J Virol 77:3816–3823

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Liu D, Shi W, Shi Y et al (2013) Origin and diversity of novel avian influenza A H7N9 viruses causing human infection: phylogenetic, structural and coalescent analyses. Lancet 381:1926–1932

    Article  PubMed  Google Scholar 

  • Liu Y, Childs RA, Matrosovich T et al (2010) Altered receptor specificity and cell tropism of D222G hemagglutinin mutants isolated from fatal cases of pandemic A(H1N1) 2009 influenza virus. J Virol 84:12069–12074

    Article  PubMed Central  PubMed  Google Scholar 

  • Lu X, Tumpey TM, Morken T et al (1999) A mouse model for the evaluation of pathogenesis and immunity to influenza A (H5N1) viruses isolated from humans. J Virol 73:5903–5911

    PubMed Central  PubMed  CAS  Google Scholar 

  • Ma W, Belisle SE, Mosier D et al (2011) 2009 pandemic H1N1 influenza virus causes disease and upregulation of genes related to inflammatory and immune responses, cell death, and lipid metabolism in pigs. J Virol 44:11626–11637. doi:10.1128/JVI.05705-11

    Article  CAS  Google Scholar 

  • Maines TR, Lu XH, Erb SM et al (2005) Avian influenza (H5N1) viruses isolated from humans in Asia in 2004 exhibit increased virulence in mammals. J Virol 79:11788–11800

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Mansfield KG (2007) Viral tropism and the pathogenesis of influenza in the mammalian host. Am J Pathol 171:1089–1092

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Manzoor R, Sakoda Y, Nomura N 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 83:1572–1578

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Martin CM, Cunin CM, Gottlieb LS et al (1959) Asian influenza A in Boston 1957-58. I. Observations in thirty-two influenza-associated fatal cases. Arch Intern Med 103:515–531

    Article  CAS  Google Scholar 

  • McAuley JL, Tate MD, MacKenzie-Kludas CJ (2013) Activation of the NLRP3 inflammasome by IAV virulence protein PB1-F2 contributes to severe pathophysiology and disease. PLoS Pathog 9(5):e1003392. doi:10.1371/journal.ppat.1003392.Epub

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Meunier I, von Messling V (2012) PB1-F2 modulates early host responses but does not affect the pathogenesis of H1N1 seasonal influenza virus. J Virol 86(8):4271–4278. doi:10.1128/JVI.07243-11

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Mok CK, Lee HH, Lestra M et al (2014) Amino-acid substitutions in polymerase basic protein 2 gene contributes to the pathogenicity of the novel A/H7N9 influenza virus in mammalian hosts. J Virol 2014 Jan 8. [Epub ahead of print]

    Google Scholar 

  • Morens DM, Taubenberger JK, Fauci AS (2013) H7N9 avian influenza A virus and the perpetual challenge of potential human pandemicity. mBio 4(4):e00445–13. doi:10.1128/mBio.00445-13

  • Mukherjee S, Majumdar S, Vipat VC et al (2012) Non structural protein of avian influenza A (H11N1) virus is a weaker suppressor of immune responses but capable of inducing apoptosis in host cells. Virol J 9(1):149

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Mulder J, Hers JFP (1972) Influenza. Wolters-Noordhoff, Groningen

    Google Scholar 

  • Neumann G, Kawaoka Y (2006) Host range restriction and pathogenicity in the context of influenza pandemic. Emerg Infect Dis 12:881–886

    Article  PubMed Central  PubMed  Google Scholar 

  • Ogiwara H, Yasui F, Munekata K et al (2014) Histopathological evaluation of the diversity of cells susceptible to H5N1 virulent avian influenza virus. Am J Pathol 184(1):171–183

    Article  PubMed  CAS  Google Scholar 

  • Nin N, Sanchez-Rodriguez C, Ver LS (2012) Lung histopathological findings in fatal pandemic influenza A (H1N1). Med Intensiva 36(1):24–31

    Article  PubMed  CAS  Google Scholar 

  • OIE (2005). www.oie.int

  • Ozawa M, Basnet S, Burley LM et al (2011) Impact of amino acid mutations in PB2, PB1-F2, and NS1 on the replication and pathogenicity of pandemic (H1N1) 2009 influenza viruses. J Virol 85(9):4596–4601

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Peiris JS, Yu WC, Leung CW et al (2004) Re-emergence of fatal human influenza A subtype H5N1 disease. Lancet 21:617–619

    Article  Google Scholar 

  • Peitsch C, Klenk HD, Garten W et al (2014) Activation of influenza A viruses by host proteases from swine airway epithelium. J Virol 88(1):282–291

    Article  PubMed  CAS  Google Scholar 

  • Perdue ML, Suarez DL (2000) Structural features of the avian influenza virus hemagglutinin that influence virulence. Vet Microbiol 74:77–86

    Article  PubMed  CAS  Google Scholar 

  • Ping J, Dankar SK, Forbes NE et al (2010) PB2 and hemagglutinin mutations are major determinants of host range and virulence in mouse-adapted influenza A virus. J Virol 84:10606–10618

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Pothlichet J, Meunier I, Davis BK et al (2013) Type I IFN triggers RIG-I/TLR3/NLRP3-dependent inflammasome activation in influenza A virus infected cells. PLoS Pathog 9(4):e1003256. doi: 10.1371/journal.ppat.1003256. Epub 2013 Apr 11

  • Puthavathana P, Auewarakul P, Charoenying PC et al (2005) Molecular characterization of complete genome of human influenza H5N1 virus isolate from Thailand. J Gen Virol 86:423–433

    Article  PubMed  CAS  Google Scholar 

  • Rajsbaum R, Albrecht RA, Wang MK et al (2012) Species-specific inhibition of RIG-I Ubiquitination and IFN induction by the influenza A Virus NS1 protein. PLoS Pathog 8:e1003059

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Reperant LA, van de Bildt MW, van Amerongen G et al (2011) Highly pathogenic avian influenza virus H5N1 infection in a long-distance migrant shorebird under migratory and non-migratory states. PLoS ONE 6(11):e27814

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Rimmelzwaan GF, Kuiken T, Amerongen GV et al (2001) Pathogenesis of influenza A (H5N1) virus infection in a primate model. J Virol 75:6687–6691

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Rodrigue-Gervais IG, Labbé K, Dagenais Maryse et al (2014) Cellular inhibitor of apoptosis protein cIAP2 protects against pulmonary tissue necrosis during influenza virus infection to promote host survival. Cell Host Microbe 15:23–35

    Article  PubMed  CAS  Google Scholar 

  • Rolling T, Koerner I, Zimmermann P et al (2009) Adaptive mutations resulting in enhanced polymerase activity contribute to high virulence of influenza A virus in mice. J Virol 83:6673–6680

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Rott R, Orlich M, Scholtissek C (1979) Correlation of pathogenicity and gene constellation of influenza A virus. III. Non-pathogenic recombimants derived from highly pathogenic parent strains. J Gen Virol 44:471–477

    Article  PubMed  CAS  Google Scholar 

  • Ru YX, Li YC, Zhao Y et al (2011) Multiple organ invasion by viruses: pathological characteristics in three fatal cases of the 2009 pandemic influenza A/H1N1. Ultrastruct Pathol 35:155–161. doi:10.3109/01913123.2011.574249

    Article  PubMed  Google Scholar 

  • Rudge JW, Coker R (2013) Human to human transmission of H7N9. Br Med J 347. BMJ 2013;347:f4730 doi: http://dx.doi.org/10.1136/bmj.f4730 (Published 6 August 2013)

  • Sakabe S, Ozawa M, Takano R et al (2011) Mutations in PA, NP, and HA of a pandemic (H1N1) 2009 influenza virus contribute to its adaptation to mice. Virus Res 158:124–129

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Schrauwen EJA, de Graaf M, Herfst S et al (2013) Determinants of virulence of influenza A virus. Eur J Clin Microbiol & Infect Dis 9:1–12

    Google Scholar 

  • Schultz CS, Koci M, Thompson E et al (2003) Examining the cellular pathways involved in influenza virus induced apoptosis. Avian Dis 47(Special issue):968–971

    Google Scholar 

  • Schultz-Cherry S, Krug RM, Hinshaw VS (1998) Induction of apoptosis by influenza virus. Semin Virol 8:491–495

    Article  CAS  Google Scholar 

  • Schultz-Cherry S, Dybdahl-Sissoko N, Neumann G et al (2001) Influenza virus NS1 protein induces apoptosis in cultured cells. J Virol 75(17):7875–7881

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Seo SH, Hoffmann E, Webster RG (2002) Lethal H5N1 influenza viruses escape host anti-viral cytokine responses. Nat Med 8:950–954

    Article  PubMed  CAS  Google Scholar 

  • Seo SH, Hoffmann E, Webster RG (2004) The NS1 gene of H5N1 influenza viruses circumvents host anti-viral cytokine responses. Virus Res 103:107–113

    Article  PubMed  CAS  Google Scholar 

  • Shiley KT, Nadolski G, Mickus T et al (E2010) Differences in the epidemiological characteristics and clinical outcomes of pandemic (H1N1) 2009 influenza, compared with seasonal influenza. Infect Cntrl Hosp Epidemiol 31:676–682

    Google Scholar 

  • Shinya K, Hamm S, Hatta M et al (2004) PB2 amino acid at position 627 affects replicative eficiency, but not cell tropism, of Hong Kong H5N1 influenza A viruses in mice. Virology 320:258–266

    Article  PubMed  CAS  Google Scholar 

  • Shortridge KF, Zhou NN, Guan Y et al (1998) Characterization of avian H5N1 influenza viruses from poultry in Hong Kong. Virology 252:331–342

    Article  PubMed  CAS  Google Scholar 

  • Soloff AC, Bissel SJ, Junecko BF et al (2014) Massive mobilization of dendritic cells in H5N1 influenza virus infection of nonhuman primates. J Infect Dis 2014 Jan 7. [Epub ahead of print]

    Google Scholar 

  • Song J, Feng H, Xu J et al (2011) The PA protein directly contributes to the virulence of H5N1 avian influenza viruses in domestic ducks. J Virol 85(5):2180–2188. doi:10.1128/JVI.01975-10

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Soubies SM, Volmer C, Croville G et al (2010) Species-specific contribution of the four C-terminal amino acids of influenza A virus NS1 protein to virulence. J Virol 84(13):6733–6747. doi:10.1128/JVI.02427-09

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Srinivasan K, Raman R, Jayaraman A et al (2013) Quantitative description of glycan-receptor binding of influenza A virus H7 hemagglutinin. PLoS ONE 8(2):e49597. doi: 10.1371/journal.pone.0049597

  • Stech O, Veits J, Weber S et al (2009) Acquisition of a polybasic hemagglutinin cleavage site by a low-pathogenic avian influenza virus is not sufficient for immediate transformation into a highly pathogenic strain. J Virol 83:5864–5868

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Suarez DL, Perdue ML, Cox N et al (1998) Comparison of highly virulent H5N1 influenza viruses isolated from humans and chickens from Hong Kong. J Virol 72:6678–6688

    PubMed Central  PubMed  CAS  Google Scholar 

  • Subbarao EK, London W, Murphy BR (1993) A single amino acid in the PB2 gene of influenza A virus is a determinant of host range. J Virol 67:1761–1764

    PubMed Central  PubMed  CAS  Google Scholar 

  • Swayne DE, Halvorson DA (2003) Influenza. In: Saif YM, Barnes HJ, Fadly AM, Glisson JR, McDougald LR, Swayne DE (eds) Diseases of Poultry, 11th edn. Iowa State University Press, Ames, pp 135–160

    Google Scholar 

  • Sweet C, Bird RA, Cavanagh D et al (1979) The local origin of the febrile response induced in ferrets during respiratory infection with a virulent influenza virus. Br J Exp Pathol 60:300–308

    PubMed Central  PubMed  CAS  Google Scholar 

  • Tateno I, Suzuki S, Nakamura S et al (1965) Rapid diagnosis of influenza by means of fluorescent antibody technic. I. Some basic informations. Jpn J Exp Med 35:383–400

    PubMed  CAS  Google Scholar 

  • Tran AT, Rahim MN, Ranadheera C et al (2013) Knockdown of specific host factors protects against influenza virus-induced cell death. Cell Death Dis 4(8):e769

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Tse LV, Hamilton AM, Friling T et al (2014) A novel activation mechanism of avian influenza virus H9N2 by furin. J Virol 88(3):1673–1683

    Article  PubMed  CAS  Google Scholar 

  • Tumpey TM, Garcia-Sastre A, Taubenberger JK et al (2005) Pathogenicity of influenza viruses with genes from the 1918 pandemic virus: functional roles of alveolar macrophages and neutrophils in limiting virus replication and mortality in mice. J Virol 79:14933–14944

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Uiprasertkul M, Kitphati R, Puthavathana P et al (2007) Apoptosis and pathogenesis of avian influenza A (H5N1) virus in humans. Emerg Infect Dis 13(5):708–712

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Uraki R, Kiso M, Shinya K et al (2013) Virulence determinants of pandemic A(H1N1)2009 influenza virus in a mouse model. J Virol 87(4):2226–2233

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • USAHA (1994) Report of the committee on transmisible diseases of poultry and other avian species. Criteria for determining that an AI virus causing an outbreak must be considered for eradication. In: Proceedings of the 98th annual meeting of US animal health association, p 522

    Google Scholar 

  • Van Campen H, Easterday BC, Hinshae VS (1989) Virulent avian influenza A viruses: Their effect on avian lymphocytes and macrophages in vivo and in vitro. J Gen Virol 70:2887–2895

    Article  PubMed  Google Scholar 

  • Van Riel D, Munster VJ, de Wit E et al (2007) Human and avian influenza viruses target different cells in the lower respiratory tract of humans and other mammals. Am J Pathol 171:1215–1223

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Vey M, Orlich M, Adler S et al (1992) Haemmagglutinin activation of pathogenic avian influenza viruses of sertype H7 requires the protease recognition motif R-X-K/R –R. Virology 188:408–413

    Article  PubMed  CAS  Google Scholar 

  • Walker JA, Kawaoka Y (1993) Importance of conserved amino acids at the cleavage site of haemagglutinin of virulent avian influenza A virus. J Gen Virol 74:311–314

    Article  PubMed  CAS  Google Scholar 

  • Wan H, Perez DR (2007) Amino acid 226 in the hemagglutinin of H9N2 influenza viruses determines cell tropism and replication in human airway epithelial cells. J Virol 81:5181–5191

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Wang Q, Zhang S, Jiang H et al (2012) PA from an H5N1 highly pathogenic avian influenza virus activates viral transcription and replication and induces apoptosis and interferon expression at an early stage of infection. Virol J 9(1):106

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Watanabe T, Shinya K, Watanabe S et al (2011) Avian-type receptor-binding ability can increase influenza virus pathogenicity in macaques. J Virol 85:13195–13203

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Webster RG, Rott R (1987) Influenza virus A pathogenicity: The pivotal role of hemagglutinin. Cell 50:665–666

    Article  PubMed  CAS  Google Scholar 

  • WHO (2013) Overview of the emergence and characteristics of the avian influenza A(H7N9) virus 1–38 http://www.who.int/influenza/human_animal_interface/influenza_h7n9/WHO_H7N9_review_31May13.pdf

  • Wood GW, McCauley JW, Bashiruddin JB et al (1993) Deduced amino acid sequences at the haemagglutinin cleavage site of avian influenza A viruses of H5 and H7 subtypes. Arch Virol 130:209–217

    Article  PubMed  CAS  Google Scholar 

  • Wu C, Cheng X, Wang X et al (2013) Clinical and molecular characteristics of the 2009 pandemic influenza H1N1 infection with severe or fatal disease from 2009 to 2011 in Shenzhen, China. J Med Virol 85(3):405–412. doi:10.1002/jmv.23295

    Article  PubMed  CAS  Google Scholar 

  • Xu L, Bao L, Deng W et al (2013) The mouse and ferret models for studying the novel avian-origin human influenza A (H7N9) virus. Virology Journal 10:1–10. doi:10.1186/1743-422X-10-253

    Article  CAS  Google Scholar 

  • Xu L, Bao L, Lv Q et al (2010) A single-amino-acid substitution in the HA protein changes the replication and pathogenicity of the 2009 pandemic A (H1N1) influenza viruses in vitro and in vivo. Virol J 7:325

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Xu L, Bao L, Zhou J et al (2011) Genomic polymorphism of the pandemic A (H1N1) influenza viruses correlates with viral replication, virulence, and pathogenicity in vitro and in vivo. PLoS ONE 44:e20698. doi:10.1371/journal.pone.0020698

    Article  CAS  Google Scholar 

  • Yamayoshi S, Yamada S, Fukuyama S et al (2014) Virulence-affecting amino acid changes in the PA protein of H7N9 influenza A viruses. J Virol JVI-03155

    Google Scholar 

  • Ye J, Sorrell EM, Cai Y et al (2010) Variations in the hemagglutinin of the 2009 H1N1 pandemic virus: Potential for strains with altered virulence phenotype? PLoS Pathog 6:e1001145

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Yen HL, Aldridge JR, Boon ACM et al (2009) Changes in H5N1 influenza virus hemagglutinin receptor binding domain affect systemic spread. Proc Natl Acad Sci USA 106:286–291

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Yuan R, Cui J, Zhang S et al (2014) Pathogenicity and transmission of H5N1 avian influenza viruses in different birds. Vet Microbiol 168(1):50–59

    Article  PubMed  Google Scholar 

  • Zablockiene B, Ambrozaitis A, Kacergius C et al (2012) Implication of nitric oxide in the pathogenesis of influenza virus infection. Biologija 58(1):15–25

    Article  CAS  Google Scholar 

  • Zamarin D, Ortigoza MB, Palese P (2006) Influenza A virus PB1-F2 protein contributes to viral pathogenesis in mice. J Virol 80:7976–7983

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Zambon MC (1999) Epidemiology and pathogenesis of influenza. J Antimicrob Chemother 44(suppl 2):3–9

    Article  PubMed  CAS  Google Scholar 

  • Zhang H, Hale BG, Xu K et al (2013) Viral and host factors required for avian H5N1 influenza A virus replication in mammalian cells. Viruses 5(6):1431–1446

    Article  PubMed Central  PubMed  Google Scholar 

  • Zhou B, Li Y, Halpin R et al (2011) PB2 residue 158 is a pathogenic determinant of pandemic H1N1 and H5 influenza A viruses in mice. J Virol 85:357–365

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Zhou J, Wang D, Gao R et al (2013) Biological features of novel avian influenza A (H7N9) virus. Nature 499(7459):500–503

    Article  PubMed  CAS  Google Scholar 

  • Zielecki F, Semmler I, Kalthoff D et al (2010) Virulence determinants of avian H5N1 influenza A virus in mammalian and avian hosts: role of the C-terminal ESEV motif in the viral NS1 protein. J Virol 84(20):10708–10718

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Zimmermann P, Manz B, Haller O et al (2011) The viral nucleoprotein determines Mx sensitivity of influenza A viruses. J Virol 85:8133–8140

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Zitzow LA, Rowe T, Morken T et al (2002) Pathogenesis of avian influenza A (H5N1) viruses in ferrets. J Virol 76:4420–4429

    Article  PubMed Central  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Veterinary Microbiology, LLR University of Veterinary and Animal Sciences, Hisar, 125004, Haryana, India

    Sanjay Kapoor

  2. Division of Pathology, Indian Veterinary Research Institute (IVRI), Izatnagar, Bareilly, 243122, Uttar Pradesh, India

    Kuldeep Dhama

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  1. Sanjay Kapoor
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Kapoor, S., Dhama, K. (2014). Pathogenesis and Pathogenicity of Influenza Viruses. In: Insight into Influenza Viruses of Animals and Humans. Springer, Cham. https://doi.org/10.1007/978-3-319-05512-1_8

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