Multiorgan distribution of human influenza A virus strains observed in a mouse model
- 246 Downloads
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.
KeywordsInfluenza Influenza Virus Avian Influenza MDCK Cell Influenza Infection
The authors are thankful to Jana Mesárošová and Matilda Némethová for their excellent technical assistance and Katarína Polčicová for reading the manuscript. This work was supported by the Scientific Grant Agency of the Ministry of Education of the Slovak Republic and the Slovak Academy of Sciences, grant nos. 2/7065/27, 2/6077/27, 2/0154/09 and by the Slovak Research and Development Agencyn under contract no. APVV-51-021605.
- 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.Russ G, Varečková E, Styk B (1974) Steric effects in the reaction of influenza virus neuraminidase with antibodies. Acta Virol 18:299–306Google Scholar
- 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
- 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