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Journal of Virology, March 2003, p. 3816-3823, Vol. 77, No. 6
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.6.3816-3823.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Neurovirulence in Mice of H5N1 Influenza Virus Genotypes Isolated from Hong Kong Poultry in 2001

Aleksandr S. Lipatov,1 Scott Krauss,1 Yi Guan,2 Malik Peiris,2 Jerold E. Rehg,3 Daniel R. Perez,1 and Robert G. Webster1,4*

Division of Virology, Department of Infectious Diseases,1 Department of Pathology, St. Jude Children's Research Hospital,3 Department of Pathology, University of Tennessee, Memphis, Tennessee 38105,4 Department of Microbiology, University of Hong Kong, Hong Kong Special Administrative Region, Hong Kong, People's Republic of China2

Received 30 August 2002/ Accepted 3 December 2002

We studied the pathogenicity of five different genotypes (A to E) of highly pathogenic avian H5N1 viruses, which contained HA genes similar to those of the H5N1 virus A/goose/Guangdong/1/96 and five different combinations of "internal" genes, in a mouse model. Highly pathogenic, neurotropic variants of genotypes A, C, D, and E were isolated from the brain after a single intranasal passage in mice. Genotype B virus was isolated from lungs only. The mouse brain variants had amino acid changes in all gene products except PB1, NP, and NS1 proteins but no common sets of mutations. We conclude that the original H5N1/01 isolates of genotypes A, C, D, and E were heterogeneous and that highly pathogenic neurotropic variants can be rapidly selected in mice.

* Corresponding author. Mailing address: Division of Virology, Department of Infectious Diseases, St. Jude Children's Research Hospital, 332 North Lauderdale St., Memphis, TN 38105-2794. Phone: (901) 495-3400. Fax: (901) 523-2622. E-mail: robert.webster{at}stjude.org.

Journal of Virology, March 2003, p. 3816-3823, Vol. 77, No. 6
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.6.3816-3823.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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