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Evolutionary characterization of the six internal genes of H5N1 human influenza A virus

Department of Virology I, National Institute of Infectious Diseases, 23-1, Toyama 1-chome, Shinjuku-ku, Tokyo 162-8640, Japan¹
Government Virus Unit, Queen Mary Hospital, Department of Health, Hong Kong, China²
Epizootic Research Station, Equine Research Institute, Japan Racing Association, 1400-4 Shiba, Kokubunji-machi, Shimotsuga, Tochigi 329-04, Japan³

Author for correspondence: Kuniaki Nerome. Fax +81 3 5285 1155. e-mail knerome{at}nih.go.jp

The entire nucleotide sequences of all six internal genes of six human H5N1 influenza A viruses isolated in Hong Kong in 1997 were analysed in detail from a phylogenetic point of view and compared with the evolutionary patterns of the haemagglutinin and neuraminidase genes. Despite being isolated within a single year in the same geographical location, human H5N1 viruses were characterized by a variety of amino acid substitutions in the ribonucleoprotein complex [PB2, PB1, PA and nucleoprotein (NP)] as well as the matrix (M) proteins 1 and 2 and nonstructural (NS) proteins 1 and 2. The presence of previously reported amino acid sequences specific for human strains was confirmed in the PB2, PA, NP and M2 proteins. Nucleotide and amino acid sequence identities of the six internal genes of H5N1 viruses examined here were separated into at least two variant groups. In agreement with the above result, phylogenetic trees of the six internal genes of human H5N1 viruses were generally composed of two minor clades. Additionally, variable dendrogram topologies suggested that reassortment among viruses contributed further to the genetic variability of these viruses. As a result, it became clear that human H5N1 viruses are characterized by divergent gene constellations, suggesting the possible occurrence of genetic reassortment between viruses of the two evolutionary lineages.

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