This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Yen, H.-L.
Right arrow Articles by Webster, R. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yen, H.-L.
Right arrow Articles by Webster, R. G.

 Previous Article  |  Next Article 

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.



This article has been cited by other articles:

  • Lycett, S. J., Ward, M. J., Lewis, F. I., Poon, A. F. Y., Kosakovsky Pond, S. L., Brown, A. J. L. (2009). Detection of Mammalian Virulence Determinants in Highly Pathogenic Avian Influenza H5N1 Viruses: Multivariate Analysis of Published Data. J. Virol. 83: 9901-9910 [Abstract] [Full Text]  
  • Rich, S. M., Leendertz, F. H., Xu, G., LeBreton, M., Djoko, C. F., Aminake, M. N., Takang, E. E., Diffo, J. L. D., Pike, B. L., Rosenthal, B. M., Formenty, P., Boesch, C., Ayala, F. J., Wolfe, N. D. (2009). From the Cover: The origin of malignant malaria. Proc. Natl. Acad. Sci. USA 106: 14902-14907 [Abstract] [Full Text]  
  • Jackson, S., Van Hoeven, N., Chen, L.-M., Maines, T. R., Cox, N. J., Katz, J. M., Donis, R. O. (2009). Reassortment between Avian H5N1 and Human H3N2 Influenza Viruses in Ferrets: a Public Health Risk Assessment. J. Virol. 83: 8131-8140 [Abstract] [Full Text]  
  • Maines, T. R., Jayaraman, A., Belser, J. A., Wadford, D. A., Pappas, C., Zeng, H., Gustin, K. M., Pearce, M. B., Viswanathan, K., Shriver, Z. H., Raman, R., Cox, N. J., Sasisekharan, R., Katz, J. M., Tumpey, T. M. (2009). Transmission and Pathogenesis of Swine-Origin 2009 A(H1N1) Influenza Viruses in Ferrets and Mice. Science 325: 484-487 [Abstract] [Full Text]  
  • Van Hoeven, N., Pappas, C., Belser, J. A., Maines, T. R., Zeng, H., Garcia-Sastre, A., Sasisekharan, R., Katz, J. M., Tumpey, T. M. (2009). Human HA and polymerase subunit PB2 proteins confer transmission of an avian influenza virus through the air. Proc. Natl. Acad. Sci. USA 106: 3366-3371 [Abstract] [Full Text]  
  • Yen, H.-L., Aldridge, J. R., Boon, A. C. M., Ilyushina, N. A., Salomon, R., Hulse-Post, D. J., Marjuki, H., Franks, J., Boltz, D. A., Bush, D., Lipatov, A. S., Webby, R. J., Rehg, J. E., Webster, R. G. (2009). Changes in H5N1 influenza virus hemagglutinin receptor binding domain affect systemic spread. Proc. Natl. Acad. Sci. USA 106: 286-291 [Abstract] [Full Text]  
  • Belser, J. A., Blixt, O., Chen, L.-M., Pappas, C., Maines, T. R., Van Hoeven, N., Donis, R., Busch, J., McBride, R., Paulson, J. C., Katz, J. M., Tumpey, T. M. (2008). Contemporary North American influenza H7 viruses possess human receptor specificity: Implications for virus transmissibility. Proc. Natl. Acad. Sci. USA 105: 7558-7563 [Abstract] [Full Text]  
  • Korteweg, C., Gu, J. (2008). Pathology, Molecular Biology, and Pathogenesis of Avian Influenza A (H5N1) Infection in Humans. Am. J. Pathol. 172: 1155-1170 [Abstract] [Full Text]  
  • Wu, W. L., Chen, Y., Wang, P., Song, W., Lau, S.-Y., Rayner, J. M., Smith, G. J. D., Webster, R. G., Peiris, J. S. M., Lin, T., Xia, N., Guan, Y., Chen, H. (2008). Antigenic Profile of Avian H5N1 Viruses in Asia from 2002 to 2007. J. Virol. 82: 1798-1807 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»