Cited by 88Influenza Virus Research StudiesRespiratory viral infections researchVirology and Viral Diseases

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

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Safronetz, David, Rockx, Barry, Feldmann, Friederike, Belisle, Sarah E., Palermo, Robert E., Brining, Douglas, Gardner, Don, Proll, Sean C. +21 more·2011·Journal of Virology

Abstract

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.

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Crossref · 10.1128/jvi.01848-10

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  • In a macaque infection model, clinically distinct Mexican isolates of SOIV showed an increase in IL-6, TNF, and IL-1beta gene expression in the lungs and pronounced levels of IL-6 and MCP-1 in the plasma.

    “In a macaque infection model, clinically distinct Mexican isolates of SOIV showed an increase in IL-6, TNF, and IL-1␤ gene expression in the lungs and pronounced levels of IL-6 and MCP-1 in the plasma (123).”

    From Into the Eye of the Cytokine Storm (2012) · cites this paper as [123]

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Authors
Safronetz, D., Rockx, B., Feldmann, F., Belisle, S. E., Palermo, R. E., Brining, D., Gardner, D., Proll, S. C., Marzi, A., Tsuda, Y., LaCasse, R. A., Kercher, L., York, A., Korth, M. J., Long, D., Rosenke, R., Shupert, W. L., Aranda, C. A., Mattoon, J. S., Kobasa, D., Kobinger, G., Li, Y., Taubenberger, J. K., Richt, J. A., Parnell, M., Ebihara, H., Kawaoka, Y., Katze, M. G., & Feldmann, H.
Affiliations
  • Laboratory of Virology (Hamilton, Montana)
  • University of Washington (US)
  • Rocky Mountain Veterinary Branch (Hamilton, Montana)
  • Instituto de Diagnóstico y Referencia Epidemiológicos, Prolongación de Carpio No. 470, 3er Piso, Col. Santo Tomas, Delegación Muguel Hidalgo, Mexico City, CP 11340, Mexico
  • Washington State University (US)
  • Public Health Agency of Canada (CA)
  • National Institutes of Health (US)
  • Department of Diagnostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, Kansas
  • University of Wisconsin–Madison (US)
Venue
Journal of Virology
Published
2011-02
Volume
85
Issue
3
Pages
1214-1223
ISSN
  • 0022-538X (ISSN-L)
  • 1098-5514
OpenAlex
W2061904548
Cited by
86
References
39
Citations by year
2025: 2 · 2023: 2 · 2022: 1 · 2021: 1 · 2020: 5 · 2019: 6 · 2018: 6 · 2017: 4 · 2016: 2 · 2015: 9 · 2014: 12 · 2013: 9 · 2012: 19
FWCI
8.87
Type
journal article
Language
en
Open access
Locations
  • Journal of Virology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
Funders
  • Division of Intramural Research, National Institute of Allergy and Infectious Diseases
  • University of Washington
  • Public Health Agency of Canada
  • Public Health Agency
  • National Institutes of Health (HHSN272200800060C, HHSN266200700010C, 8r24od011157-10)
  • Japan Science and Technology Agency
  • National Institute of Allergy and Infectious Diseases (HHSN266200700010C, HHSN272200800060C)
  • National Center for Research Resources (R24RR016354, P51RR000166)
  • Exploratory Research for Advanced Technology
  • NHLBI Division of Intramural Research
Topics
  • Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
  • Health Sciences › Medicine › Epidemiology › Respiratory viral infections research
  • Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
Keywords
virulence, cynomolgus macaque model, nonhuman primate model, pneumonia, respiratory infections, host transcriptional response, cytokine response, viral replication, disease progression, histopathology
MeSH terms
Animals, Child, Preschool, Disease Models, Animal, Humans, Influenza, Human, Macaca, Male, Orthomyxoviridae Infections, Pneumonia, Viral, Respiratory Tract Infections, Severity of Illness Index, Genetic Variation, Virulence, Cytokines, Primate Diseases, Disease Progression, Gene Expression Profiling, Influenza A Virus, H1N1 Subtype

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