tetano
Editor, Senior Moderator
J Virol. 2010 Nov 17. [Epub ahead of print]
Pandemic Swine-Origin H1N1 Influenza A Isolates Show Heterogeneous Virulence in Macaques.
Safronetz D, Rockx B, Feldmann F, Belisle SE, Palermo RE, Brining D, Gardner D, Proll SC, Marzi A, Tsuda Y, Lacasse RA, Kercher L, York A, Korth MJ, Long D, Rosenke R, Shupert WL, Alpuche Aranda C, Mattoon JS, Kobasa D, Kobinger G, Li Y, Taubenberger JK, Richt JA, Parnell M, Ebihara H, Kawaoka Y, Katze MG, Feldmann H.
Laboratory of Virology (Hamilton, MT), Rocky Mountain Veterinary Branch (Hamilton, MT), and Laboratory of Infectious Diseases (Bethesda, MD), Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, USA; Department of Microbiology, School of Medicine and Washington National Primate Research Center, University of Washington, Seattle, WA, USA; Instituto de Diagn?stico y Referencia Epidemiol?gicos (InDRE), Prolongaci?n de Carpio No. 470, 3er piso, Col. Santo Tomas, Delegaci?n Muguel Hidalgo, Mexico City, CP 11340, Mexico; Department of Veterinary Clinical Sciences, Washington State University, Pullman, WA, USA; SpecialPathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada; Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA; Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan; Influenza Research Institute, Dept. of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53711, USA; ERATO Infection-Induced Host Responses Project, Saitama 332-0012 Japan; Creative Research Initiative, Sousei, Hokkaido University, Sapporo 060-0818, Japan.
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. Here we 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 infection 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.
PMID: 21084481 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/21084481
Pandemic Swine-Origin H1N1 Influenza A Isolates Show Heterogeneous Virulence in Macaques.
Safronetz D, Rockx B, Feldmann F, Belisle SE, Palermo RE, Brining D, Gardner D, Proll SC, Marzi A, Tsuda Y, Lacasse RA, Kercher L, York A, Korth MJ, Long D, Rosenke R, Shupert WL, Alpuche Aranda C, Mattoon JS, Kobasa D, Kobinger G, Li Y, Taubenberger JK, Richt JA, Parnell M, Ebihara H, Kawaoka Y, Katze MG, Feldmann H.
Laboratory of Virology (Hamilton, MT), Rocky Mountain Veterinary Branch (Hamilton, MT), and Laboratory of Infectious Diseases (Bethesda, MD), Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, USA; Department of Microbiology, School of Medicine and Washington National Primate Research Center, University of Washington, Seattle, WA, USA; Instituto de Diagn?stico y Referencia Epidemiol?gicos (InDRE), Prolongaci?n de Carpio No. 470, 3er piso, Col. Santo Tomas, Delegaci?n Muguel Hidalgo, Mexico City, CP 11340, Mexico; Department of Veterinary Clinical Sciences, Washington State University, Pullman, WA, USA; SpecialPathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada; Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA; Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan; Influenza Research Institute, Dept. of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53711, USA; ERATO Infection-Induced Host Responses Project, Saitama 332-0012 Japan; Creative Research Initiative, Sousei, Hokkaido University, Sapporo 060-0818, Japan.
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. Here we 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 infection 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.
PMID: 21084481 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/21084481