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BIOLOGICAL SCIENCES / MICROBIOLOGY
Lack of transmission of H5N1 avian–human reassortant influenza viruses in a ferret model
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*Influenza Branch, Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333; Centro Nacional de Biotecnologia, Consejo Superior de Investigaciones Científicas, 28049 Madrid, Spain; ||National Institute of Hygiene and Epidemiology, Hanoi, Vietnam; and **Center for Biomedical and Pharmaceutical Research and Development, Ministry of Health, Jakarta 10560, Indonesia
Communicated by Peter Palese, Mount Sinai School of Medicine, New York, NY, June 23, 2006 (received for review May 23, 2006)
Avian influenza A H5N1 viruses continue to spread globally among birds, resulting in occasional transmission of virus from infected poultry to humans. Probable human-to-human transmission has been documented rarely, but H5N1 viruses have not yet acquired the ability to transmit efficiently among humans, an essential property of a pandemic virus. The pandemics of 1957 and 1968 were caused by avian–human reassortant influenza viruses that had acquired human virus-like receptor binding properties. However, the relative contribution of human internal protein genes or other molecular changes to the efficient transmission of influenza viruses among humans remains poorly understood. Here, we report on a comparative ferret model that parallels the efficient transmission of H3N2 human viruses and the poor transmission of H5N1 avian viruses in humans. In this model, an H3N2 reassortant virus with avian virus internal protein genes exhibited efficient replication but inefficient transmission, whereas H5N1 reassortant viruses with four or six human virus internal protein genes exhibited reduced replication and no transmission. These findings indicate that the human virus H3N2 surface protein genes alone did not confer efficient transmissibility and that acquisition of human virus internal protein genes alone was insufficient for this 1997 H5N1 virus to develop pandemic capabilities, even after serial passages in a mammalian host. These results highlight the complexity of the genetic basis of influenza virus transmissibility and suggest that H5N1 viruses may require further adaptation to acquire this essential pandemic trait.
transmissibility | pandemic virus properties | pandemic influenza | animal model | receptor specificity
Present address: Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences Animal Influenza Laboratory, Harbin, Heilongjiang 150001, China.
Present address: Emerging Pathogens Department, Southern Research Institute, Birmingham, AL 35205.
¶Present address: Centro Nacional de Microbiologia, Instituto de Salud Carlos III, Majadahonda, 28220 Madrid, Spain.
Present address: Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
Author contributions: T.R.M., T.R., N.J.C., K.S., and J.M.K. designed research; T.R.M. and L.-M.C. performed research; Y.M., H.C., J.O., A.F., N.T.H., L.Q.M., E.R.S., R.O.D., and S.H. contributed new reagents/analytic tools; T.R.M., K.S., and J.M.K. analyzed data; and T.R.M., T.M.T., K.S., and J.M.K. wrote the paper.
Conflict of interest statement: No conflicts declared.
To whom correspondence should be addressed. E-mail: jkatz{at}cdc.gov
© 2006 by The National Academy of Sciences of the USA
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