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

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 patter ns of the haemagglutinin and neuraminidase genes. Despite being isolated wi thin a single year in the same geographical location, human H5N1 viruses we re characterized by a variety of amino acid substitutions in the ribonucleo protein 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 se quence identities of the six internal genes of H5N1 viruses examined here w ere 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 dendro gram topologies suggested that reassortment among viruses contributed furth er to the genetic variability of these viruses. As a result, it became clea r that human H5N1 viruses are characterized by divergent gene constellation s, suggesting the possible occurrence of genetic reassortment between virus es of the two evolutionary lineages.