Transmission and Pathogenesis of Swine-Origin 2009 A(H1N1) Influenza Viruses in Ferrets and Mice -- Maines et al., 10.1126/science.1177238 -- Science
Reports
Submitted on June 3, 2009
Accepted on June 23, 2009
Transmission and Pathogenesis of Swine-Origin 2009 A(H1N1) Influenza Viruses in Ferrets and Mice
Taronna R. Maines 1, Akila Jayaraman 2, Jessica A. Belser 3, Debra A. Wadford 1, Claudia Pappas 1, Hui Zeng 1, Kortney M. Gustin 1, Melissa B. Pearce 1, Karthik Viswanathan 2, Zachary H. Shriver 2, Rahul Raman 2, Nancy J. Cox 1, Ram Sasisekharan 2, Jacqueline M. Katz 1, Terrence M. Tumpey 1*
1 Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
2 Harvard-MIT Division of Health Sciences and Technology and Koch Institute for Integrative Cancer Research, Department of Biological Engineering, Massachusetts Institute of Technology, E25-519, Cambridge, MA 02139, USA.
3 Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA.
* To whom correspondence should be addressed. Terrence M. Tumpey , E-mail: tft9@cdc.gov
Recent reports of mild to severe influenza-like illness in humans caused by a novel swine-origin 2009 A(H1N1) influenza virus underscore the need to better understand the pathogenesis and transmission of these viruses in mammals. Here, selected 2009 A(H1N1) isolates were assessed for their ability to cause disease in mice and ferrets, and compared with a contemporary seasonal H1N1 virus for their ability to transmit by respiratory droplets to na?ve ferrets. In contrast to seasonal influenza H1N1 virus, 2009 A(H1N1) viruses caused increased morbidity, replicated to higher titers in lung tissue, and were recovered from the intestinal tract of intranasally inoculated ferrets. The 2009 A(H1N1) viruses exhibited less efficient respiratory droplet transmission in ferrets in comparison to the high-transmissible phenotype of a seasonal H1N1 virus. Transmission of the 2009 A(H1N1) viruses was further corroborated by characterizing the binding specificity of the viral hemagglutinin to the sialylated glycan receptors (in the human host) using dose-dependent direct receptor binding and human lung tissue binding assays.
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<cite cite="http://www.sciencemag.org/cgi/content/abstract/sci;1177238v1?maxtoshow=&HITS=10&hits=10&RESULTFOR MAT=&fulltext=pandemic+influenza&searchid=1&FIRSTI NDEX=0&sortspec=date&resourcetype=HWCIT">Transmission and Pathogenesis of Swine-Origin 2009 A(H1N1) Influenza Viruses in Ferrets and Mice -- Maines et al., 10.1126/science.1177238 -- Science</cite>
Submitted on June 3, 2009
Accepted on June 23, 2009
Transmission and Pathogenesis of Swine-Origin 2009 A(H1N1) Influenza Viruses in Ferrets and Mice
Taronna R. Maines 1, Akila Jayaraman 2, Jessica A. Belser 3, Debra A. Wadford 1, Claudia Pappas 1, Hui Zeng 1, Kortney M. Gustin 1, Melissa B. Pearce 1, Karthik Viswanathan 2, Zachary H. Shriver 2, Rahul Raman 2, Nancy J. Cox 1, Ram Sasisekharan 2, Jacqueline M. Katz 1, Terrence M. Tumpey 1*
1 Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
2 Harvard-MIT Division of Health Sciences and Technology and Koch Institute for Integrative Cancer Research, Department of Biological Engineering, Massachusetts Institute of Technology, E25-519, Cambridge, MA 02139, USA.
3 Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA.
* To whom correspondence should be addressed. Terrence M. Tumpey , E-mail: tft9@cdc.gov
Recent reports of mild to severe influenza-like illness in humans caused by a novel swine-origin 2009 A(H1N1) influenza virus underscore the need to better understand the pathogenesis and transmission of these viruses in mammals. Here, selected 2009 A(H1N1) isolates were assessed for their ability to cause disease in mice and ferrets, and compared with a contemporary seasonal H1N1 virus for their ability to transmit by respiratory droplets to na?ve ferrets. In contrast to seasonal influenza H1N1 virus, 2009 A(H1N1) viruses caused increased morbidity, replicated to higher titers in lung tissue, and were recovered from the intestinal tract of intranasally inoculated ferrets. The 2009 A(H1N1) viruses exhibited less efficient respiratory droplet transmission in ferrets in comparison to the high-transmissible phenotype of a seasonal H1N1 virus. Transmission of the 2009 A(H1N1) viruses was further corroborated by characterizing the binding specificity of the viral hemagglutinin to the sialylated glycan receptors (in the human host) using dose-dependent direct receptor binding and human lung tissue binding assays.
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