Characterization of the pathogenicity of members of the newly established H9N2 influenza virus lineages in Asia

The reported transmission of avian H9N2 influenza viruses to humans and the isolation of these viruses from Hong Kong poultry markets lend urgency to studies of their ecology and pathogenicity. We found that H9N2 viruses from North America differ from those of Asia. The North American viruses, which infect primarily domestic turkeys, replicated poorly in inoculated chicken s. Phylogenetic analysis of the hemagglutinin and nucleoprotein genes indic ated that the Asian H9N2 influenza viruses could he divided into three subl ineages. Initial biological characterization of at least one virus from eac h lineage was done in animals. Early isolates of one lineage (A/Chicken/Bei jing/1/94, H9N2) caused as high as 80% mortality rates in inoculated chicke ns, whereas all other strains were nonpathogenic. Sequence analysis showed that some isolates, including the pathogenic isolate, had one additional ba sic amino acid (A-R/K-S-S-R-) at the hemagglutinin cleavage site. Later iso lates of the same lineage (A/Chicken/Hong Kong/G9/97, H9N2) that contains t he PB1 and PB2 genes similar to Hong Kong/97 H5N1 viruses replicated in chi ckens, ducks, mice, and pigs but were pathogenic only in mice. A/Quail/Hong Kong/G1/97 (H9N2), from a second lineage that possesses the replicative co mplex similar to Hong Kong/97 H5N1 virus, replicated in chickens and ducks without producing disease signs, was pathogenic in mice, and spread to the brain without adaptation. Examples of the third Asian H9N2 sublineage (A/Ch icken/Korea/323/96, Duck/Hong Kong/Y439/97) replicated in chickens, ducks, and mice without producing disease signs. The available evidence supports t he notion of differences in pathogenicity of H9N2 viruses in the different lineages and suggests that viruses possessing genome segments similar to 19 97 H5N1-like viruses are potentially pathogenic in mammals. (C) 2000 Academ ic Press.