Neurovirulence in Mice of H5N1 Influenza Virus Genotypes Isolated

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. The outbreak of avian influenza A virus of subtype H5N1 in Hong Kong in 1997 killed 6 of 18 infected persons (4, 5, 35) and was the first documented case of direct transmission of avian influenza virus from poultry to humans. The outbreak led to the development of serious lethal diseases and was regarded by some as an incipient pandemic situation (27). The slaughter of all poultry in live poultry markets in Hong Kong in Decem