J Virol. 2007 Apr 25; [Epub ahead of print]
Inefficient Transmission of H5N1 Influenza Viruses in a Ferret Contact Model.
Yen HL, Lipatov AS, Ilyushina NA, Govorkova EA, Franks J, Yilmaz N, Douglas A, Hay A, Krauss S, Rehg JE, Hoffmann E, Webster RG.
Departments of Infectious Diseases (Division of Virology) and Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Department of Virology, Refik Saydam Hygiene Institute, Cemal Gursel cad. No 18 Sihhiye-Ankara, 06100 Turkey; Division of Virology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
The ability to infect and transmit efficiently among humans is essential for a novel influenza A virus to cause pandemic. To evaluate the pandemic potential of widely disseminated H5N1 influenza virus, a ferret contact model that comprised of one inoculated and two contact ferrets was used to study the transmissibility of four human H5N1 viruses isolated during 2003-2006. The effects of viral pathogenicity and receptor binding specificity (affinity to synthetic sialosaccharides with alpha2,3- or alpha2,6-linkages) on transmissibility were assessed. A/Vietnam/1203/04 and A/Vietnam/JP36-2/05 viruses, which possess "avian-like" alpha2,3-linked sialic acid (SA) receptor specificity, caused neurological symptoms and death in ferrets inoculated with 10(3) TCID50. A/HongKong/213/03 and A/Turkey/65-596/06 viruses, which show binding affinity for "human-like" alpha2,6-linked SA receptors in addition to their affinity for alpha2,3-linked SA receptors, caused mild clinical symptoms and were not lethal to ferrets. No transmission of A/Vietnam/1203/04 or A/Turkey/65-596/06 viruses was detected. One contact ferret developed neutralizing antibodies to A/HongKong/213/03 in the absence of clinical signs or detectable virus shedding. In two groups, one of two naive contact ferrets had detectable virus after 6 to 8 days housing 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 naive ferret that was housed together. Our results suggest that despite their receptor binding affinity, circulating H5N1 viruses retain molecular determinants that restrict their spread among mammalian species. |
