Influenza Virus: A Brief Overview



Influenza is a major public health concern, infecting 5–15% of the global population annually. Influenza virus belongs to family Orthomyxoviridae, and has three types A, B and C. Infection by influenza virus A is most common and severe, generally found in humans. It spreads rapidly and affects human population across large geographical region within short period of time with varying degree of pathology from mild to severe. Wild aquatic birds and other animal species like birds, pigs, ferret, horses, seals, whales, mink, giant anteaters, cats and dogs are the reservoir for the influenza A virus. Influenza B and C viruses have very limited host range and appear predominantly in humans. Influenza virus gains pandemic potential through genetic reassortment called “genetic shift” with complete renewal of surface antigen and a small but gradual genetic change by mutations which make it to adapt efficiently in human population called “genetic drift”. Although, the epidemiology related to influenza infection has been studied from several years but some facts associated to disease transmission has poorly understood. This article reviews the important aspects of virological, epidemiological and clinical features related to influenza virus for better understanding of disease transmission and its pathogenesis.


Influenza virus H1N1 Pathogenesis Epidemiology Pandemic Swine flu 


  1. 1.
    Dawood F, Jain S, Finelli L et al., Novel Swine-Origin Influenza A (H1N1) Virus Investigation Team (2009) Emergence of a novel swine-origin influenza A (H1N1) virus in humans. N Engl J Med 360:2605–2615Google Scholar
  2. 2.
    Reed C, Angulo FJ, Swerdlow DL et al (2009) Estimates of the prevalence of pandemic (H1N1) 2009, United States, April–July 2009. Emerg Infect Dis 15:7–2004CrossRefGoogle Scholar
  3. 3.
    Donaldson LJ, Rutter PD, Ellis BM et al (2009) Mortality from pandemic A/H1N12009 influenza in England: public health surveillance study. Br Med J 339:b5213CrossRefGoogle Scholar
  4. 4.
    Li KS, Guan Y, Wang J et al (2004) Genesis of a highly pathogenic and potentially pandemic H5N1 influenza virus in eastern Asia. Nature 430:209–213PubMedCrossRefGoogle Scholar
  5. 5.
    Cox NJ, Subbarao K (2000) Global epidemiology of influenza: past and present. Annu Rev Med 51:407–421PubMedCrossRefGoogle Scholar
  6. 6.
    Treanor JJ (2005) Influenza virus. In: Mandell GL, Bennett JE, Dolin R (eds) Principles and practice of infectious diseases, vol 2. Elsevier, Philadelphia, pp 2060–2085Google Scholar
  7. 7.
    World Health Organization (2009) Pandemic influenza (H1N1) 2009 Update 75. Accessed 8 July 2011
  8. 8.
    Fields BN, Knipe DM, Howley PM (2007) Fields virology. Wolters Kluwer Health/Lippincott Williams & Wilkins, PhiladelphiaGoogle Scholar
  9. 9.
    Chen W et al (2007) A novel influenza A virus mitochondrial protein that induces cell death. Nat Med 7:1306–1312CrossRefGoogle Scholar
  10. 10.
    Matrosovich MN, Matrosovich TY, Gray T et al (2004) Human and avian influenza viruses target different cell types in cultures of human airway epithelium. Proc Natl Acad Sci USA 101:4620–4624PubMedCrossRefGoogle Scholar
  11. 11.
    Nayak DP, Hui EK, Barman S (2004) Assembly and budding of influenza virus. Virus Res 106:147–165PubMedCrossRefGoogle Scholar
  12. 12.
    Wilson IA, Skehel JJ, Wiley DC (1981) Structure of the haemagglutinin membrane glycoprotein of influenza virus at 3 Å resolutions. Nature 289:366–373PubMedCrossRefGoogle Scholar
  13. 13.
    Skehel JJ, Wiley DC (2000) Receptor binding and membrane fusion in virus entry: the influenza hemagglutinin. Annu Rev Biochem 69:531–569PubMedCrossRefGoogle Scholar
  14. 14.
    Harrison SC (2008) Viral membrane fusion. Nat Struct Mol Biol 15:690–698PubMedCrossRefGoogle Scholar
  15. 15.
    Pinto LH, Lamb RA (2006) The M2 proton channels of influenza A and B viruses. J Biol Chem 281:8997–9000PubMedCrossRefGoogle Scholar
  16. 16.
    Wang C, Lamb RA, Pinto LH (1995) Activation of the M2 ion channel of influenza virus: a role for the transmembrane domain histidine residue. Biophys J 69:1363–1371PubMedCrossRefGoogle Scholar
  17. 17.
    Wu WWW, Pante N (2009) The directionality of the nuclear transport of the influenza A genome is driven by selective exposure of nuclear localization sequences on nucleoprotein. Virol J 6:68PubMedCrossRefGoogle Scholar
  18. 18.
    Portela A, Digard P (2002) The influenza virus nucleoprotein: a multifunctional RNA binding protein pivotal to virus replication. J Gen Virol 83:723–734PubMedGoogle Scholar
  19. 19.
    Sanz-Ezquerro JJ, Zurcher T, de la Luna S, Ortin J, Nieto A (1996) The amino-terminal one-third of the influenza virus PA protein is responsible for the induction of proteolysis. J Virol 70:1905–1911PubMedGoogle Scholar
  20. 20.
    Ulmanen I, Broni BA, Krug RM (1981) The role of two of the influenza virus core P proteins in recognizing cap 1 structures (m 7 GpppNm) on RNAs and in initiating viral RNA transcription. Proc Natl Acad Sci USA 78:7355–7359PubMedCrossRefGoogle Scholar
  21. 21.
    Plotch SJ, Bouloy M, Ulmanen I, Krug RM (1981) A unique cap (m 7 GpppXm) dependent influenza virion endonuclease cleaves capped RNAs to generate the primers that initiate viral RNA transcription. Cell 23:847–858PubMedCrossRefGoogle Scholar
  22. 22.
    Hagen M, Chung TDDY, Butcher A, Krystal M (1991) Recombinant influenza virus polymerase: requirement of both 5 and 3 viral ends for endonuclease activity. J Virol 68:1509–1515Google Scholar
  23. 23.
    WHO (2005) Avian influenza: assessing the pandemic threat. WHO, GenevaGoogle Scholar
  24. 24.
    Lazzari S, Stohr K (2004) Avian influenza and influenza pandemics. Bull World Health Organ 82:242PubMedGoogle Scholar
  25. 25.
    Simonsen L, Clarke MJ, Schonberger LB, Arden NH, Cox NJ, Fukuda K (1998) Pandemic versus epidemic influenza mortality: a pattern of changing age distribution. J Infect Dis 178:53–60PubMedGoogle Scholar
  26. 26.
    Glezen WP (1996) Emerging infections: pandemic influenza. Epidemiol Rev 18:64–76PubMedGoogle Scholar
  27. 27.
    Morens DM, Taubenberger JK, Fauci AS (2009) The persistent legacy of the 1918 influenza virus. N Engl J Med 361:225–229PubMedCrossRefGoogle Scholar
  28. 28.
    Brockwell-Staats C, Webster RG, Webby RJ (2009) Diversity of influenza viruses in swine and the emergence of a novel human pandemic influenza A (H1N1). Influenza Other Respi Viruses 3:207–213PubMedCrossRefGoogle Scholar
  29. 29.
    World Health Organization (WHO) (2009) World now at the start of 2009 influenza pandemic. Accessed 8 July 2011
  30. 30.
    Fraser C, Donnelly CA, Cauchemez S et al (2009) Pandemic potential of a strain of influenza A (H1N1): early findings. Science 324:1557PubMedCrossRefGoogle Scholar
  31. 31.
    Hancock K, Veguilla V, Lu X et al (2009) Cross-reactive antibody responses to the 2009 pandemic H1N1 influenza virus. N Engl J Med 361:1–8CrossRefGoogle Scholar
  32. 32.
    Gras S, Kedzierski L, Valkenburg S et al (2010) Cross-reactive CD81 T-cell immunity between the pandemic H1N1–2009 and H1N1–1918 influenza A viruses. Proc Natl Acad Sci USA 107:12599–12604PubMedCrossRefGoogle Scholar
  33. 33.
    Garten RJ, Davis CT, Russell CA, Shu B, Lindstrom S, Balish A et al (2009) Antigenic and genetic characteristics of swine-origin 2009 A (H1N1) influenza viruses circulating in humans. Science 325:197–201PubMedCrossRefGoogle Scholar
  34. 34.
    Sym D, Patel PM, Chaar GM (2009) Seasonal, avian and novel H1N1 influenza: prevention and treatment modalities. Ann Pharmacother 43:2001–2011PubMedCrossRefGoogle Scholar
  35. 35.
    Debre R, Couvreur J (1970) Influenza: clinical features. In: Debre R, Celers J (eds) Clinical virology: the evaluation and management of human viral infections. WB Saunders, Philadelphia, pp 507–515Google Scholar
  36. 36.
    Harper SA, Bradley JS, Englund JA et al (2009) Seasonal influenza in adults and children: diagnosis, treatment, chemoprophylaxis and institutional outbreak management: clinical practice guidelines of the Infectious Diseases Society of America. Clin Infect Dis 48:1003–1032PubMedCrossRefGoogle Scholar
  37. 37.
    Cunha BA (2010) Pneumonia essentials, 3rd edn. Jones & Bartlett, SudburyGoogle Scholar
  38. 38.
    Jain S, Kamimoto L, Bramley AM et al (2009) Hospitalized patients with 2009 H1N1 influenza in the United States, April–June 2009. N Engl J Med 361:1935–1944PubMedCrossRefGoogle Scholar
  39. 39.
    Munster VJ, de Wit E, van den Brand JM et al (2009) Pathogenesis and transmission of swine origin 2009 A(H1N1) influenza virus in ferrets. Science 325:481–483PubMedGoogle Scholar
  40. 40.
    Shieh WJ, Blau DM, Denison AM et al (2010) Pandemic influenza A (H1N1): pathology and pathogenesis of 100 fatal cases in the United States. Am J Pathol 177:166–175PubMedCrossRefGoogle Scholar
  41. 41.
    Gill JR, Sheng Z, Ely SF et al (2010) Pulmonary pathological findings of fatal 2009 pandemic influenza A/H1N1 viral infections. Arch Pathol Lab Med 134:225–243Google Scholar
  42. 42.
    Bender BS, Small PA Jr (1992) Influenza: pathogenesis and host defense. Semin Respir Infect 7:38–45PubMedGoogle Scholar
  43. 43.
    Fesq H, Bacher M, Nain M, Gemsa D (1994) Programmed cell death (apoptosis) in human monocytes infected by influenza A virus. Immunobiology 190:175–182PubMedCrossRefGoogle Scholar
  44. 44.
    Julkunen I, Melen K, Nyqvist M, Pirhonen J, Sareneva T, Matikainen S (2000) Inflammatory responses in influenza A virus infection. Vaccine 19(Suppl 1):S32–S37PubMedCrossRefGoogle Scholar
  45. 45.
    Julkunen I, Sareneva T, Pirhonen J, Ronni T, Melen K, Matikainen S (2001) Molecular pathogenesis of influenza A virus infection and virus-induced regulation of cytokine gene expression. Cytokine Growth Factor Rev 12:171–180PubMedCrossRefGoogle Scholar
  46. 46.
    Woo PC, Tung ET, Chan KH, Lau CC, Lau SK, Yuen KY et al (2010) Cytokine profiles induced by the novel swine-origin influenza A/H1N1 virus: implications for treatment strategies. J Infect Dis 201:346–353PubMedCrossRefGoogle Scholar
  47. 47.
    Hung KK, Li IF et al (2010) Delayed clearance of viral load and marked cytokine activation in severe cases of pandemic H1N1 2009 influenza virus infection. Clin Infect Dis 50:850–859PubMedCrossRefGoogle Scholar
  48. 48.
    Cheung CY, Poon LL, Lau AS, Luk W, Lau YL, Shortridge KF, Gordon S, Guan Y, Peiris JS (2002) Induction of proinflammatory cytokines in human macrophages by influenza A (H5N1) viruses: a mechanism for the unusual severity of human disease?. Lancet 360:1831–1837PubMedCrossRefGoogle Scholar
  49. 49.
    Perrone LA, Plowden JK, Garcia-Sastre A, Katz JM, Tumpey TM (2008) H5N1 and 1918 pandemic influenza virus infection results in early and excessive infiltration of macrophages and neutrophils in the lungs of mice. PLoS Pathog 4:E1000115PubMedCrossRefGoogle Scholar
  50. 50.
    Guan Y, Poon LL, Cheung CY, Ellis TM, Lim W, Lipatov AS, Chan KH, Sturm-Ramirez KM, Cheung CL, Leung YH et al (2004) H5N1 influenza: a protean pandemic threat. Proc Natl Acad Sci USA 101:8156–8161PubMedCrossRefGoogle Scholar
  51. 51.
    Kochs G, Garcia-Sastre A, Martinez-Sobrido L (2007) Multiple anti-interferon actions of the influenza A virus NS1 protein. J Virol 81:7011–7021PubMedCrossRefGoogle Scholar
  52. 52.
    Lee SM, Cheung CY, Nicholls JM, Hui KP, Leung CY, Uiprasertkul M, Tipoe GL, Lau YL, Poon LL, Ip NY et al (2008) Hyperinduction of cyclooxygenase-2-mediated proinflammatory cascade: a mechanism for the pathogenesis of avian influenza H5N1 infection. J Infect Dis 198:525–535PubMedCrossRefGoogle Scholar
  53. 53.
    Hui KPY, Lee SMY, Cheung C, Ng IHY, Poon LLM et al (2009) Induction of proinflammatory cytokines in primary human macrophages by influenza A virus (H5N1) Is selectively regulated by IFN regulatory factor 3 and p38 MAPK. J Immunol 182:1088–1098PubMedGoogle Scholar
  54. 54.
    Centers for Disease Control and Prevention (CDC) (2009) Interim guidance for the detection of novel influenza A virus using rapid influenza diagnostic tests. CDC, AtlantaGoogle Scholar
  55. 55.
    Centers for Disease Control and Prevention (CDC) (2009) Interim recommendations for clinical use of influenza diagnostic tests during 2009–10 influenza season. Accessed 8 July 2011
  56. 56.
    Palese P, Shaw ML (2007) Orthomyxoviridae: the viruses and their replication. In: Knipe DM, Howley PM (eds) Fields virology. Lippincott Williams & Wilkins, Philadelphia, pp 1647–1689Google Scholar
  57. 57.
    CDC (2009) Update: influenza activity—United States, September 28, 2008–April 4, 2009, and composition of the 2009–2010 influenza vaccine. Morb Mortal Wkly Rep 58:369–374Google Scholar
  58. 58.
    Le MT, Wertheim HF, Nguyen HD 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:e3339PubMedCrossRefGoogle Scholar
  59. 59.
    Le QM, Kiso M, Someya K et al (2005) Avian flu: isolation of drug-resistant H5N1 virus. Nature 437:1108PubMedCrossRefGoogle Scholar
  60. 60.
    Itoh Y, Shinya K, Kiso M et al (2009) In vitro and in vivo characterization of new swine-origin H1N1 influenza viruses. Nature 460:1021–1025PubMedGoogle Scholar
  61. 61.
    CDC (2009) Update: drug susceptibility of swine-origin influenza A (H1N1) viruses, April 2009. Morb Mortal Wkly Rep 58:433–435Google Scholar
  62. 62.
    World Health Organization (WHO) (2009) Pandemic (H1N1) 2009—update 70 virological surveillance data. Accessed 8 July 2011
  63. 63.
    Hoffmann HH, Palese P, Shaw ML (2008) Modulation of influenza virus replication by alteration of sodium ion transport and protein kinase C activity. Antivir Res 80:124–134PubMedCrossRefGoogle Scholar
  64. 64.
    Ludwig S (2009) Targeting cell signalling pathways to fight the flu: towards a paradigm change in anti-influenza therapy. J Antimicrob Chemother 64:1–4PubMedCrossRefGoogle Scholar
  65. 65.
    WHO information meeting on influenza vaccine composition for the Northern Hemisphere 2009–2010 and round-table discussion on matters relating to influenza vaccine development and production. WHO headquarters, Executive Board Room, GenevaGoogle Scholar
  66. 66.
    Barr IG, McCauley J, Cox N, Daniels R et al (2010) Epidemiological, antigenic and genetic characteristics of seasonal influenza A(H1N1), A(H3N2) and B influenza viruses: basis for the WHO recommendation on the composition of influenza vaccines for use in the 2009–2010 Northern Hemisphere season. Vaccine 28:1156–1167Google Scholar
  67. 67.
    CDC article (2009) 2008–2009 influenza season week 21 ending May 30, 2009. Accessed 5 June 2009
  68. 68.
    WHO. Recommended composition of influenza virus vaccines for use in the 2010 southern hemisphere influenza seasonGoogle Scholar
  69. 69.
    Centres for Disease Control and Prevention (2009) Update: Influenza A (H1N1) 2009 monovalent vaccines. Morb Mortal Wkly Rep 58:1100–1101Google Scholar
  70. 70.
    Johnson NP, Mueller J (2002) Updating the accounts: global mortality of the 1918–1920 “Spanish” influenza pandemic. Bull Hist Med 76:105–115PubMedCrossRefGoogle Scholar

Copyright information

© The National Academy of Sciences, India 2012

Authors and Affiliations

  1. 1.Postgraduate Department of MicrobiologyCSM Medical UniversityLucknowIndia

Personalised recommendations