Archives of Virology

, Volume 154, Issue 3, pp 409–419

Multiorgan distribution of human influenza A virus strains observed in a mouse model

  • T. Fislová
  • M. Gocník
  • T. Sládková
  • V. Ďurmanová
  • J. Rajčáni
  • E. Varečková
  • V. Mucha
  • F. Kostolanský
Original Article

Abstract

Multiorgan spread and pathogenesis of influenza infection with three human influenza A viruses was studied in mice. Mouse-adapted viruses A/Dunedin/4/73(H3N2), A/Mississippi/1/85(H3N2), and A/PR/8/34(H1N1) differed considerably in virulence (p.f.u./LD50): 79,000 p.f.u. for Dunedin, 5,000 p.f.u. for Mississippi, and 65 p.f.u. for PR/8, which qualified Dunedin as low virulent, Mississippi as intermediate, and PR/8 as highly virulent. All three viruses were detected in lungs, heart, and thymus by cultivation and RT-PCR. Moreover, vRNA of all viruses was found in liver and spleen, of Dunedin and PR/8 also in kidneys and that of Dunedin and Mississippi in blood. Only vRNA of Dunedin was demonstrated in brain. Lung damage accompanied by histopathological changes and thymus reduction were most extensive after infection with the highly virulent virus PR/8. We assume that the ability to spread to multiple organs may be a more common property of influenza viruses in mammalian hosts than previously believed.

References

  1. 1.
    Lu X, Tumpey TM, Morken T, Zaki SR, Cox NJ, Katz JM (1999) A mouse model for the evaluation of pathogenesis and immunity to influenza A (H5N1) viruses isolated from humans. J Virol 73:5903–5911PubMedGoogle Scholar
  2. 2.
    Gao P, Watanabe S, Ito T, Goto H, Wells K, McGregor M, Cooley AJ, Kawaoka Y (1999) Biological heterogeneity, including systemic replication in mice, of H5N1 influenza A virus isolates from humans in Hong Kong. J Virol 73:3184–3189PubMedGoogle Scholar
  3. 3.
    Nishimura H, Itamura S, Iwasaki T, Kurata T, Tashiro M (2000) Characterization of human influenza A (H5N1) virus infection in mice: neuro-, pneumo- and adipotropic infection. J Gen Virol 81:2503–2510PubMedGoogle Scholar
  4. 4.
    Bright RA, Cho DS, Rowe T, Katz JM (2003) Mechanisms of pathogenicity of influenza A (H5N1) viruses in mice. Avian Dis 47:1131–1134PubMedCrossRefGoogle Scholar
  5. 5.
    Skehel JJ, Wiley DC (2000) Receptor binding and membrane fusion in virus entry: the influenza Hemagglutinin. Annu Rev Biochem 69:531–569PubMedCrossRefGoogle Scholar
  6. 6.
    Ward AC (1997) Virulence of influenza A virus for mouse lungs. Virus Genes 14:187–194PubMedCrossRefGoogle Scholar
  7. 7.
    Brown EG (2000) Influenza virus genetics. Biomed & Pharmacother 54:196–209CrossRefGoogle Scholar
  8. 8.
    Reina J (2002) Factors affecting the virulence and pathogenicity of avian and human viral strains (influenza virus type A). Enferm Infecc Microbiol Clin 20:346–353PubMedGoogle Scholar
  9. 9.
    Matrosovich MN, Matrosovich TY, Gray T, Roberts NA, Klenk HD (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
  10. 10.
    Matrosovich MN, Matrosovich TY, Uhlendorff J, Garten W, Klenk HD (2007) Avian-virus-like receptor specificity of the hemagglutinin impedes influenza virus replication in cultures of human airway epithelium. Virology 362:384–390CrossRefGoogle Scholar
  11. 11.
    Yokota S (2003) Influenza-associated encephalopathy-pathophysiology and disease mechanisms. Nippon Rinsho 61:1953–1958PubMedGoogle Scholar
  12. 12.
    Togashi T, Matsuzono Y, Narita M, Morishima T (2004) Influenza-associated acute encephalopathy in Japanese children in 1994–2002. Virus Res 103:75–78PubMedCrossRefGoogle Scholar
  13. 13.
    Salonen O, Koshkiniemi M, Saari A, Myllylä V, Pyhälä R, Airaksinen L, Vaheri A (1997) Myelitis associated with influenza A virus infection. J Neurovirol 3:83–85PubMedCrossRefGoogle Scholar
  14. 14.
    Agyeman P, Duppenthaler A, Heininger U, Aebi C (2004) Influenza-associated myositis in children. Infection 32:199–203PubMedCrossRefGoogle Scholar
  15. 15.
    Sano T (2006) Influenza myocarditis and pericarditis. Nippon Rinsho 64:1916–1920PubMedGoogle Scholar
  16. 16.
    Reye RDK, Morgan G, Basal J (1963) Encephalopathy and fatty degeneration of the viscera. A disease entity in childhood. Lancet 2:749–762PubMedCrossRefGoogle Scholar
  17. 17.
    Tsuruoka H, Xu H, Kuroda K, Hosaka Y (1997) Viremia in influenza: detection by polymerase chain reaction. Nippon Rinsho 55:2714–2718PubMedGoogle Scholar
  18. 18.
    Wright PF, Neumann G, Kawaoka Y (2001) Orthomyxoviruses, Chap. 48. In: Knipe DM, Howley PM (eds) Fields virology, vol 2, 5th edn. Lippincott Willaims & Wilkins, Philadelphia, pp 1691–1740Google Scholar
  19. 19.
    Russ G, Varečková E, Styk B (1974) Steric effects in the reaction of influenza virus neuraminidase with antibodies. Acta Virol 18:299–306Google Scholar
  20. 20.
    Kostolanský F, Mucha V, Slováková R, Varečková E (2002) Natural influenza A virus infection of mice elicits strong antibody response to HA2 glycopolypeptide. Acta Virol 46:229–236PubMedGoogle Scholar
  21. 21.
    Varečková E, Wharton SA, Mucha V, Gocník M, Kostolanský F (2003) A monoclonal antibody specific to the HA2 glycoprotein of influenza A virus hemagglutinin that inhibits its fusion activity reduces replication of the virus. Acta Virol 47:229–236PubMedGoogle Scholar
  22. 22.
    Tkáčová M, Varečková E, Baker IC, Love JM, Ziegler T (1997) Evaluation of monoclonal antibodies for subtyping of currently circulating human type A influenza viruses. J Clin Microbiol 35:1196–1198PubMedGoogle Scholar
  23. 23.
    Varečková E, Betáková T, Soláriková L, Kostolanský F, Waris M, Russ G (1995) Preparation of monoclonal antibodies for the diagnosis of influenza A infection using different immunization protocols. J Immunol Method 180:107–116CrossRefGoogle Scholar
  24. 24.
    Varečková E, Blaškovičová H, Gocník M, Mikas J, Adamčáková J, Fislová T, Kostolanský F, Mucha V (2006) Evaluation of clinical specimens for influenza A positivity using various diagnostic methods. Acta Virol 50:181–186PubMedGoogle Scholar
  25. 25.
    Tkáčová M, Varečková E (1996) A sensitive one-step immunocapture EIA for rapid diagnosis of influenza A. J Virol Methods 60:65–71PubMedCrossRefGoogle Scholar
  26. 26.
    Van Reeth K (2000) Cytokines in the pathogenesis of influenza. Vet Microbiol 74:109–116PubMedCrossRefGoogle Scholar
  27. 27.
    La Gruta NL, Kedzierska K, Stambas J, Doherty PC (2007) A question of self-preservation: immunopathology in influenza virus infection. Immunol Cell Biol 85:85–92PubMedCrossRefGoogle Scholar
  28. 28.
    Semenkov VF, Ageeva ON, Lavrov VF, Korotkov AA, Khodakova LP (1985) Effect of the host’s body genotype and phenotype on the manifestation of the pathogenetic properties of the influenza virus. Vopr Virusol 30:159–163PubMedGoogle Scholar
  29. 29.
    Wyde PR, Couch RB, Mackler BF, Cate TR, Levy BM (1977) Effets of low- and high-passage influenza virus infection in normal and nude mice. Infect Immun 15:221–229PubMedGoogle Scholar
  30. 30.
    Surh CD, Sprent J (1994) T-cell apoptosis detected in situ during positive and negative selection in the thymus. Nature 372:100–103PubMedCrossRefGoogle Scholar
  31. 31.
    Mori I, Komatsu T, Takeuchi K, Nakakuki K, Sudo M, Kimura Y (1995) In vivo induction of apoptosis by influenza virus. J Gen Virol 76:2869–2873PubMedCrossRefGoogle Scholar
  32. 32.
    Maines TR, Lu XH, Erb SM, Edwards L, Guarner J, Greer PW, Nguyen DC, Szretter KJ, Chen LM, Thawatsupha P, Chittaganpitch M, Waicharoen S, Nguyen DT, Nguyen T, Nguyen HH, Kim JH, Hoang LT, Kang C, Phuong LS, Lim W, Zaki S, Donis RO, Cox NJ, Katz JM, Tumpey TM (2005) Avian influenza (H5N1) viruses isolated from humans in Asia in 2004 exhibit increased virulence in mammals. J Virol 79:11788–11800PubMedCrossRefGoogle Scholar
  33. 33.
    Madjid M, Aboshady I, Awan I, Litovsky S, Casscells SW (2004) Influenza and cardiovascular disease: is there a causal relatonship? Tex Heart Inst J 31:4–13PubMedGoogle Scholar
  34. 34.
    Nolte KB, Alakija P, Oty G, Shaw MW, Subbarao K, Guarner J, Shieh WJ, Dawson JE, Morken T, Cox NJ, Zaki SR (2000) Influenza A virus infection complicated by fatal myocarditis. Am J Forensic Med Pathol 21:375–379PubMedCrossRefGoogle Scholar
  35. 35.
    Burch GE, Walsh JJ, Mogabgab W (1961) A study of the response of the cardiovascular system to Asian influenza. Am Rev Respir Dis 83:68–78PubMedGoogle Scholar
  36. 36.
    Greaves K, Oxford JS, Price CP, Clarke GH, Crake T (2003) The prevalence of myocarditis and skeletal muscle injury during acute viral infection in adults: measurement of cardiac troponins I and T in 152 patients with acute influenza infection. Arch Intern Med 163:165–168PubMedCrossRefGoogle Scholar
  37. 37.
    Beigel JH, Farrar J, Han AM, Hayden FG, Hyer R, de Jong MD, Lochindarat S, Nguyen TK, Nguyen TH, Tran TH, Nicoll A, Touch S, Yuen KY (2005) Avian influenza A (H5N1) infection in humans. N Engl J Med 353:1374–1385PubMedCrossRefGoogle Scholar
  38. 38.
    Mori SI, Nagashima M, Sasaki Y, Mori K, Tabei Y, Yoshida Y, Yamazaki K, Hirata I, Sekine H, Ito T, Suzuki S (1999) A novel amino acid substitution at the receptor-binding site on the hemagglutinin of H3N2 influenza A viruses isolated from 6 cases with acute encephalopathy during the 1997–1998 season in Tokyo. Arch Virol 144:147–155PubMedCrossRefGoogle Scholar
  39. 39.
    Takahashi M, Yamada M, Toyoda T (2001) Detection of viral antigens in the encephalopathy brain by influenza A virus. International Congress Series 1219:615–622CrossRefGoogle Scholar
  40. 40.
    Lipatov AS, Krauss S, Guan Y, Peiris M, Rehg JE, Perez DR, Webster RG (2003) Neurovirulence in mice of H5N1 influenza virus genotypes isolated from Hong Kong poultry in 2001. J Virol 77:3816–3823PubMedCrossRefGoogle Scholar
  41. 41.
    Tanaka H, Park CH, Ninomiya A, Ozaki H, Takada A, Umemura T, Kida H (2003) Neurotropism of the 1997 Hong Kong H5N1 influenza virus in mice. Vet Microbiol 95:1–13PubMedCrossRefGoogle Scholar
  42. 42.
    Muramoto Y, Le TQ, Phuong LS, Nguyen T, Nguyen TH, Sakai-Tagawa Y, Horimoto T, Kida H, Kawaoka Y (2006) Pathogenicity of H5N1 influenza A viruses isolated in Vietnam between late 2003 and 2005. J Vet Med Sci 68:735–737PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • T. Fislová
    • 1
  • M. Gocník
    • 1
  • T. Sládková
    • 1
  • V. Ďurmanová
    • 1
  • J. Rajčáni
    • 1
  • E. Varečková
    • 1
  • V. Mucha
    • 1
  • F. Kostolanský
    • 1
  1. 1.Institute of Virology, Slovak Academy of SciencesBratislavaSlovak Republic

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