{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T22:52:10Z","timestamp":1777503130720,"version":"3.51.4"},"reference-count":38,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2011,2,1]],"date-time":"2011-02-01T00:00:00Z","timestamp":1296518400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2011,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>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.<\/jats:p>","DOI":"10.1128\/jvi.01848-10","type":"journal-article","created":{"date-parts":[[2010,11,18]],"date-time":"2010-11-18T03:27:16Z","timestamp":1290050836000},"page":"1214-1223","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":81,"title":["Pandemic Swine-Origin H1N1 Influenza A Virus Isolates Show Heterogeneous Virulence in Macaques"],"prefix":"10.1128","volume":"85","author":[{"given":"David","family":"Safronetz","sequence":"first","affiliation":[{"name":"Laboratory of Virology (Hamilton, Montana)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barry","family":"Rockx","sequence":"additional","affiliation":[{"name":"Laboratory of Virology (Hamilton, Montana)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Friederike","family":"Feldmann","sequence":"additional","affiliation":[{"name":"Laboratory of Virology (Hamilton, Montana)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah E.","family":"Belisle","sequence":"additional","affiliation":[{"name":"Department of Microbiology, School of Medicine"},{"name":"Washington National Primate Research Center, University of Washington, Seattle, Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert E.","family":"Palermo","sequence":"additional","affiliation":[{"name":"Department of Microbiology, School of Medicine"},{"name":"Washington National Primate Research Center, University of Washington, Seattle, Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Douglas","family":"Brining","sequence":"additional","affiliation":[{"name":"Rocky Mountain Veterinary Branch (Hamilton, Montana)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Don","family":"Gardner","sequence":"additional","affiliation":[{"name":"Rocky Mountain Veterinary Branch (Hamilton, Montana)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sean C.","family":"Proll","sequence":"additional","affiliation":[{"name":"Department of Microbiology, School of Medicine"},{"name":"Washington National Primate Research Center, University of Washington, Seattle, Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Marzi","sequence":"additional","affiliation":[{"name":"Laboratory of Virology (Hamilton, Montana)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshimi","family":"Tsuda","sequence":"additional","affiliation":[{"name":"Laboratory of Virology (Hamilton, Montana)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel A.","family":"LaCasse","sequence":"additional","affiliation":[{"name":"Rocky Mountain Veterinary Branch (Hamilton, Montana)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Kercher","sequence":"additional","affiliation":[{"name":"Rocky Mountain Veterinary Branch (Hamilton, Montana)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anthony","family":"York","sequence":"additional","affiliation":[{"name":"Laboratory of Virology (Hamilton, Montana)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcus J.","family":"Korth","sequence":"additional","affiliation":[{"name":"Department of Microbiology, School of Medicine"},{"name":"Washington National Primate Research Center, University of Washington, Seattle, Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Long","sequence":"additional","affiliation":[{"name":"Rocky Mountain Veterinary Branch (Hamilton, Montana)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca","family":"Rosenke","sequence":"additional","affiliation":[{"name":"Rocky Mountain Veterinary Branch (Hamilton, Montana)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W. 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Santo Tomas, Delegacio\u0301n Muguel Hidalgo, Mexico City, CP 11340, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John S.","family":"Mattoon","sequence":"additional","affiliation":[{"name":"Department of Veterinary Clinical Sciences, Washington State University, Pullman, Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Darwyn","family":"Kobasa","sequence":"additional","affiliation":[{"name":"National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary","family":"Kobinger","sequence":"additional","affiliation":[{"name":"National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[{"name":"National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffery K.","family":"Taubenberger","sequence":"additional","affiliation":[{"name":"Laboratory of Infectious Diseases (Bethesda, Maryland), Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ju\u0308rgen A.","family":"Richt","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, Kansas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Parnell","sequence":"additional","affiliation":[{"name":"Rocky Mountain Veterinary Branch (Hamilton, Montana)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideki","family":"Ebihara","sequence":"additional","affiliation":[{"name":"Laboratory of Virology (Hamilton, Montana)"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshihiro","family":"Kawaoka","sequence":"additional","affiliation":[{"name":"Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan"},{"name":"Influenza Research Institute, Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin"},{"name":"ERATO Infection-Induced Host Responses Project, Saitama 332-0012 Japan"},{"name":"Creative Research Initiative, Sousei, Hokkaido University, Sapporo 060-0818, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael G.","family":"Katze","sequence":"additional","affiliation":[{"name":"Department of Microbiology, School of Medicine"},{"name":"Washington National Primate Research Center, University of Washington, Seattle, Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heinz","family":"Feldmann","sequence":"additional","affiliation":[{"name":"Laboratory of Virology (Hamilton, Montana)"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","first-page":"19237","volume":"14","year":"2009","unstructured":"Anonymous. 2009. 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