Novel Zoonotic Avian Influenza Virus A(H3N8) In Poultry In China Could Lead To A Serious Human Pandemic

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Researchers from the University of Hong Kong are warning that a current outbreak of a new zoonotic avian influenza virus among poultry and other birds in China and Hong Kong could lead to a serious human pandemic if surveillance and measures are not put into place soon.

The study findings were published in the peer reviewed journal of the U.S. CDC called Emerging Infectious Diseases.
https://wwwnc.cdc.gov/eid/article/28/10/22-1067_article

Diverse influenza A viruses are found in aquatic waterfowl, poultry, swine, horses, aquatic mammals, bats, and domestic pets such as cats and dogs. Although there is a diversity of virus hemagglutinin (H1–H16) and neuraminidase (N1–N9) subtypes in aquatic birds, more restricted numbers of virus subtypes are established in other species, including chicken (1).

The high mutation rates associated with an error-prone virus replication complex and the presence of a segmented genome enables genetic reassortment of gene segments of viruses of different species and interspecies transmission and adaptation to new hosts.

Influenza A virus subtypes H9 and H6 have formed established lineages in domestic chicken and game birds (quail, pheasant) farmed for consumption in Asia (2). The internal gene constellation of H9N2 viruses contains hemagglutinin (HA) and neuraminidase (NA) genes acquired from aquatic waterfowl to generate H5N1, H5N6, H7N9, and H10N8 viruses through genetic reassortment, and many of these viruses also became established in poultry, subsequently posing zoonotic and pandemic threats (3–5). A novel influenza A(H3N8) virus has been recently reported to cause zoonotic infection in Henan Province, China (6).

In this context, we report detection of novel H3N8 viruses recently identified in chicken in live poultry markets and chicken farms in Hong Kong, China, that are genetically similar to the zoonotic H3N8 viruses reported in mainland China (6). We also report that these recent H3N8 viruses have arisen in a manner akin to zoonotic H5N1, H7N9, and H10N8 viruses and that there is little cross-reactive immunity in the human population to these chicken H3N8 viruses.

Discussion
We report detection of chicken influenza A(H3N8) viruses from live poultry markets and farms in Hong Kong. These viruses were genetically similar to each other and to a recently reported zoonotic H3N8 virus in mainland China (6). The viruses were novel reassortants that have virus internal gene segments derived from H9N2 lineage genotype 57 viruses (A/chicken/Zhejiang/HJ/2007-like) established in poultry in mainland China, but the H3 and N8 gene segments were derived from wild aquatic bird influenza A viruses. The H9N2 virus internal gene cassette was previously reported to facilitate the emergence of reassortant influenza A viruses of zoonotic potential (26). These chicken H3N8 viruses in Hong Kong were distinct from H3N8 viruses reported from poultry in mainland China (25), but a A/chicken/China/Guangdong_01/2022 (H3N8) virus genetically similar to these viruses in all 8 gene segments is reported in public databases (Appendix Table). These H3N8 viruses were also distinct from H3N8 viruses reported in horses, dogs and cats (27–29).

These novel H3N8 viruses appear to have arisen in a manner analogous to the emergence of previous zoonotic H7N9 and H10N8 viruses, in which the H9N2 viruses enzootic in chicken and other game birds in China acquired HA and NA gene segments from wild, aquatic bird viruses. Wild aquatic birds share ecosystems with domestic ducks, and it is inevitable that influenza viruses will also be shared in such ecosystems. Subsequent trade systems in which domestic ducks and chickens (and other game birds) are mixed in close proximity within wholesale and retail poultry markets provide the opportunity for H9N2 viruses in chicken to acquire HA and NA gene segments from domestic ducks, as has been postulated in the emergence of H7N9 and H10N8 viruses (4).

Pandemics emerge when influenza viruses of birds, swine, or other mammals adapt to transmission between humans and when the human population lacks immunity to the hemagglutinin of the newly emerged virus. Cross-reactive immunity in humans is 1 parameter that is considered when risk assessing the pandemic threat from a newly emerged animal influenza virus (30). Our data suggest that there is little antigenic cross-reactivity between contemporary seasonal H3N2 viruses and the H3N8 virus. The overall HI test seroprevalence at a titer >1:40 to H3N8 in age-stratified serum samples collected from blood donors in Hong Kong was 3.2%, and the estimated proportion of the population immune (weighted for age structure) was 2.9% (95% CI 1.2%–5.8%). We estimated that if this H3N8 virus acquired transmissibility between humans and acquired an R0 >1.033, cross-reactive population immunity would fail to impede its onward transmission in the human population. For comparison, similar estimation of the minimal R0 required for the 2009 pandemic H1N1 virus to spread in face of population immunity before its emergence and spread in 2009 was 1.231 (95% CI 1.185–1.292), a markedly higher threshold to cross (22).

In conclusion, we report the emergence of a novel influenza A(H3N8) virus in chickens in Hong Kong. This virus might have major zoonotic and pandemic potential. Our results indicate the need to enhance surveillance for this virus in poultry, carry out comprehensive risk assessment of such a virus, and prepare pandemic seed vaccine strains if justified by such risk assessment.

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