Pandemic Swine-Origin H1N1 Influenza A Virus Isolates Show Heterogeneous Virulence in Macaques

被引:81
作者
Safronetz, David [1 ]
Rockx, Barry [1 ]
Feldmann, Friederike [1 ]
Belisle, Sarah E. [4 ,5 ]
Palermo, Robert E. [4 ,5 ]
Brining, Douglas [2 ]
Gardner, Don [2 ]
Proll, Sean C. [4 ,5 ]
Marzi, Andrea [1 ]
Tsuda, Yoshimi [1 ]
LaCasse, Rachel A. [2 ]
Kercher, Lisa [2 ]
York, Anthony [1 ]
Korth, Marcus J. [4 ,5 ]
Long, Dan [2 ]
Rosenke, Rebecca [2 ]
Shupert, W. Lesley [1 ]
Aranda, Celia Alpuche [6 ]
Mattoon, John S. [7 ]
Kobasa, Darwyn [8 ]
Kobinger, Gary [8 ]
Li, Yan [8 ]
Taubenberger, Jeffery K. [3 ]
Richt, Juergen A. [9 ]
Parnell, Michael [2 ]
Ebihara, Hideki [1 ]
Kawaoka, Yoshihiro [10 ,11 ,12 ,13 ]
Katze, Michael G. [4 ,5 ]
Feldmann, Heinz [1 ]
机构
[1] Virol Lab, Hamilton, MT USA
[2] Rocky Mt Vet Branch, Hamilton, MT USA
[3] NIAID, Infect Dis Lab, Bethesda, MD 20892 USA
[4] Univ Washington, Sch Med, Dept Microbiol, Seattle, WA 98195 USA
[5] Univ Washington, Washington Natl Primate Res Ctr, Seattle, WA 98195 USA
[6] Inst Diagnost & Referencia Epidemiol, Mexico City 11340, DF, Mexico
[7] Washington State Univ, Dept Vet Clin Sci, Pullman, WA 99164 USA
[8] Publ Hlth Agcy Canada, Natl Microbiol Lab, Winnipeg, MB, Canada
[9] Kansas State Univ, Coll Vet Med, Dept Diagnost Med & Pathobiol, Manhattan, KS 66506 USA
[10] Univ Tokyo, Inst Med Sci, Dept Microbiol & Immunol, Div Virol, Tokyo 1088639, Japan
[11] Univ Wisconsin, Sch Vet Med, Dept Pathobiol Sci, Influenza Res Inst, Madison, WI 53706 USA
[12] ERATO Infect Induced Host Responses Project, Kawaguchi, Saitama 3320012, Japan
[13] Hokkaido Univ, Creat Res Initiat, Sapporo, Hokkaido 0600818, Japan
基金
美国国家卫生研究院; 日本科学技术振兴机构;
关键词
IMMUNE-RESPONSE; INFECTION; DISEASE; PATHOGENESIS; HEMAGGLUTININ; TRANSMISSION; POLYMERASE; PATHOLOGY; GENOMICS; EFFICACY;
D O I
10.1128/JVI.01848-10
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
The first influenza pandemic of the new millennium was caused by a newly emerged swine-origin influenza virus (SOIV) (H1N1). This new virus is characterized by a previously unknown constellation of gene segments derived from North American and Eurasian swine lineages and the absence of common markers predictive of human adaptation. Overall, human infections appeared to be mild, but an alarming number of young individuals presented with symptoms atypical for seasonal influenza. The new SOIV also showed a sustained human-to-human transmissibility and higher reproduction ratio than common seasonal viruses, altogether indicating a higher pathogenic potential for this newly emerged virus. To study the virulence of the SOIV, we used a recently established cynomolgus macaque model and compared parameters of clinical disease, virology, host responses, and pathology/histopathology with a current seasonal H1N1 virus. We here show that infection of macaques with two genetically similar but clinically distinct SOIV isolates from the early stage of the pandemic (A/Mexico/4108/2009 and A/Mexico/InDRE4487/2009) resulted in upper and lower respiratory tract infections and clinical disease ranging from mild to severe pneumonia that was clearly advanced over the mild infection caused by A/Kawasaki/UTK-4/2009, a current seasonal strain. Unexpectedly, we observed heterogeneity among the two SOIV isolates in virus replication, host transcriptional and cytokine responses, and disease progression, demonstrating a higher pathogenic potential for A/Mexico/InDRE4487/2009. Differences in virulence may explain more severe disease, as was seen with certain individuals infected with the emerged pandemic influenza virus. Thus, the nonhuman primate model closely mimics influenza in humans.
引用
收藏
页码:1214 / 1223
页数:10
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