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Journal of Virology, November 2008, p. 10854-10863, Vol. 82, No. 21
0022-538X/08/$08.00+0     doi:10.1128/JVI.01206-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Avian Influenza H6 Viruses Productively Infect and Cause Illness in Mice and Ferrets{triangledown}

Laura Gillim-Ross,1,{dagger} Celia Santos,1 Zhongying Chen,2 Amy Aspelund,2 Chin-Fen Yang,2 Dan Ye,2 Hong Jin,2 George Kemble,2 and Kanta Subbarao1*

Laboratory of Infectious Diseases, NIAID, NIH, Bethesda, Maryland 20892,1 MedImmune, Mountain View, California 940432

Received 10 June 2008/ Accepted 5 August 2008

Influenza pandemic preparedness has focused on influenza virus H5 and H7 subtypes. However, it is not possible to predict with certainty which subtype of avian influenza virus will cause the next pandemic, and it is prudent to include other avian influenza virus subtypes in pandemic preparedness efforts. An H6 influenza virus was identified as a potential progenitor of the H5N1 viruses that emerged in Hong Kong in 1997. This virus continues to circulate in the bird population in Asia, and other H6 viruses are prevalent in birds in North America and Asia. The high rate of reassortment observed in influenza viruses and the prevalence of H6 viruses in birds suggest that this subtype may pose a pandemic risk. Very little is known about the replicative capacity, immunogenicity, and correlates of protective immunity for low-pathogenicity H6 influenza viruses in mammals. We evaluated the antigenic and genetic relatedness of 14 H6 influenza viruses and their abilities to replicate and induce a cross-reactive immune response in two animal models: mice and ferrets. The different H6 viruses replicated to different levels in the respiratory tracts of mice and ferrets, causing varied degrees of morbidity and mortality in these two models. H6 virus infection induced similar patterns of neutralizing antibody responses in mice and ferrets; however, species-specific differences in the cross-reactivity of the antibody responses were observed. Overall, cross-reactivity of neutralizing antibodies in H6 virus-infected mice did not correlate well with protection against heterologous wild-type H6 viruses. However, we have identified an H6 virus that induces protective immunity against viruses in the North American and Eurasian lineages.

* Corresponding author. Mailing address: Laboratory of Infectious Diseases, NIAID, NIH, Bldg. 33, Room 3E13C-1, 33 North Dr., MSC 3203, Bethesda, MD 20892. Phone: (301) 451-3839. Fax: (301) 496-8312. E-mail: ksubbarao{at}niaid.nih.gov

{triangledown} Published ahead of print on 20 August 2008.

{dagger} Present address: Colorado Department of Public Health & Environment, 8100 Lowry Blvd., Denver, CO 80230.

Journal of Virology, November 2008, p. 10854-10863, Vol. 82, No. 21
0022-538X/08/$08.00+0     doi:10.1128/JVI.01206-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Chen, Z., Santos, C., Aspelund, A., Gillim-Ross, L., Jin, H., Kemble, G., Subbarao, K. (2009). Evaluation of Live Attenuated Influenza A Virus H6 Vaccines in Mice and Ferrets. J. Virol. 83: 65-72 [Abstract] [Full Text]  


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