Characterization of the Pathogenicity of Members of the Newly Established H9N2 Influenza Virus Lineages in Asia

Abstract

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 chickens. Phylogenetic analysis of the hemagglutinin and nucleoprotein genes indicated that the Asian H9N2 influenza viruses could be divided into three sublineages. Initial biological characterization of at least one virus from each lineage was done in animals. Early isolates of one lineage (A/Chicken/Beijing/1/94, H9N2) caused as high as 80% mortality rates in inoculated chickens, whereas all other strains were nonpathogenic. Sequence analysis showed that some isolates, including the pathogenic isolate, had one additional basic amino acid (A-R/K-S-S-R-) at the hemagglutinin cleavage site. Later isolates of the same lineage (A/Chicken/Hong Kong/G9/97, H9N2) that contains the PB1 and PB2 genes similar to Hong Kong/97 H5N1 viruses replicated in chickens, 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 complex 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/Chicken/Korea/323/96, Duck/Hong Kong/Y439/97) replicated in chickens, ducks, and mice without producing disease signs. The available evidence supports the notion of differences in pathogenicity of H9N2 viruses in the different lineages and suggests that viruses possessing genome segments similar to 1997 H5N1-like viruses are potentially pathogenic in mammals.

Emergence of multiple genotypes of H5N1 avian influenza viruses in Hong Kong SAR

“…Data for avian viruses are more limited, but the H5N1͞97 virus and one of its precursors (H9N2, Qa͞HK͞G1͞97) cause lethal infection of mice and spread to the brain, whereas other H9N2 and H5 subtype viruses do not (23,25). Therefore, it is relevant that these new reassortant H5N1 viruses were lethal for mice without the need for prior adaptation, and that genotypes A, C, D, and E were able to spread to the brain.…”

Replication and transmission of mammalian-adapted H9 subtype influenza virus in pigs and quail

“…Members of the Eurasian lineage jumped into poultry in Asia in the late 1980s causing outbreaks. These outbreaks have occurred in land-based poultry in many countries including China, Iran, Pakistan, Lebanon, Israel and Egypt (Barbour et al, 2006;Davidson et al, 2014;Naeem et al, 1999;Nili & Asasi, 2003), and H9N2 viruses are currently endemic in poultry populations across much of Asia and the Middle East, mainly in chickens, quail and turkeys (Alexander, 2000;Guo et al, 2000;Naeem et al, 1999;Sun et al, 2010).…”

Evolution of the H9N2 influenza genotype that facilitated the genesis of the novel H7N9 virus

“…H9N2 influenza virus has low pathogenicity for avians, replicating mainly in the upper respiratory tract and causing mild or no overt signs of illness in specific pathogen-free (SPF) chickens (6). In 1994, the H9N2 subtype was first identified in chicken farms in the Guangdong province of south China (7); it has since become widespread in chickens and has caused great economic loss from reduced egg production and highly lethal coinfections (8)(9)(10)(11).…”