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Journal of Virology, July 2007, p. 6890-6898, Vol. 81, No. 13
0022-538X/07/$08.00+0     doi:10.1128/JVI.00170-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Inefficient Transmission of H5N1 Influenza Viruses in a Ferret Contact Model{triangledown}

Hui-Ling Yen,1 Aleksandr S. Lipatov,1,¶ Natalia A. Ilyushina,1 Elena A. Govorkova,1 John Franks,1 Neziha Yilmaz,2 Alan Douglas,3 Alan Hay,3 Scott Krauss,1 Jerold E. Rehg,4 Erich Hoffmann,1 and Robert G. Webster1*

Departments of Infectious Diseases (Division of Virology),1 Pathology, St. Jude Children's Research Hospital, Memphis, Tennessee,4 Department of Virology, Refik Saydam Hygiene Institute, Sihhiye-Ankara, Turkey,2 Division of Virology, National Institute for Medical Research, London, United Kingdom3

Received 25 January 2007/ Accepted 16 April 2007

The abilities to infect and transmit efficiently among humans are essential for a novel influenza A virus to cause a pandemic. To evaluate the pandemic potential of widely disseminated H5N1 influenza viruses, a ferret contact model using experimental groups comprised of one inoculated ferret and two contact ferrets was used to study the transmissibility of four human H5N1 viruses isolated from 2003 to 2006. The effects of viral pathogenicity and receptor binding specificity (affinity to synthetic sialosaccharides with {alpha}2,3 or {alpha}2,6 linkages) on transmissibility were assessed. A/Vietnam/1203/04 and A/Vietnam/JP36-2/05 viruses, which possess "avian-like" {alpha}2,3-linked sialic acid (SA) receptor specificity, caused neurological symptoms and death in ferrets inoculated with 103 50% tissue culture infectious doses. A/Hong Kong/213/03 and A/Turkey/65-596/06 viruses, which show binding affinity for "human-like" {alpha}2,6-linked SA receptors in addition to their affinity for {alpha}2,3-linked SA receptors, caused mild clinical symptoms and were not lethal to the ferrets. No transmission of A/Vietnam/1203/04 or A/Turkey/65-596/06 virus was detected. One contact ferret developed neutralizing antibodies to A/Hong Kong/213/03 but did not exhibit any clinical signs or detectable virus shedding. In two groups, one of two naïve contact ferrets had detectable virus after 6 to 8 days when housed together with the A/Vietnam/JP36-2/05 virus-inoculated ferrets. Infected contact ferrets showed severe clinical signs, although little or no virus was detected in nasal washes. This limited virus shedding explained the absence of secondary transmission from the infected contact ferret to the other naïve ferret that were housed together. Our results suggest that despite their receptor binding affinity, circulating H5N1 viruses retain molecular determinants that restrict their spread among mammalian species.

* Corresponding author. Mailing address: Department of Infectious Diseases, St. Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, TN 38105. Phone: (901) 495-3400. E-mail: robert.webster{at}stjude.org

{triangledown} Published ahead of print on 25 April 2007.

Present address: Southeast Poultry Research Laboratory, Agricultural Research Service, U.S. Department of Agriculture, 934 College Station Road, Athens, GA 30605.

Journal of Virology, July 2007, p. 6890-6898, Vol. 81, No. 13
0022-538X/07/$08.00+0     doi:10.1128/JVI.00170-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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