Genotypic evolution and antigenicity of H9N2 influenza viruses in Shanghai, China

Abstract

H9N2 influenza viruses have been circulating in China since 1994, but a systematic investigation of H9N2 in Shanghai has not previously been undertaken. Here, using 14 viruses we isolated from poultry and pigs in Shanghai during 2002 and 2006-2014, together with the commercial vaccine A/chicken/Shanghai/F/1998 (Ck/SH/F/98), we analyzed the evolution of H9N2 influenza viruses in Shanghai and showed that all 14 isolates originated from Ck/SH/F/98 antigenically. We evaluated the immune protection efficiency of the vaccine. Our findings demonstrate that H9N2 viruses in Shanghai have undergone extensive reassortment. Various genotypes emerged in 2002, 2006 and 2007, while during 2009-2014 only one genotype was found. Four antigenic groups, A-D, could be identified among the 14 isolates and a variety of antigenically distinct H9N2-virus-derived avian influenza viruses (AIVs) circulated simultaneously in Shanghai during this period. Challenge experiments using vaccinated chickens indicated that the vaccine prevented shedding of antigenic group A and B viruses, but not those of the more recent groups C and D. Genetic analysis showed that compared to the vaccine strain, representative viruses of antigenic groups C and D possess greater numbers of amino acid substitutions in the hemagglutinin (HA) protein than viruses in antigenic groups A and B. Many of these substitutions are located in antigenic sites. Our results indicate that the persistence of H9N2 AIV in China might be due to incomplete vaccine protection and that the avian influenza vaccine should be regularly evaluated and updated to maintain optimal protection.

A Global Perspective on H9N2 Avian Influenza Virus

“…Swine are often said to represent a potential 'mixing vessel' for human and avian viruses, a fact supported by semi-regular establishment of human and avian virus lineages in these hosts. There have been many recorded outbreaks of H9N2 virus in farmed pigs, mostly in Hong Kong and China [156][157][158][159]. As swine carry viruses closely related to human seasonal influenza viruses it has been hypothesised a swine influenza/H9N2 reassortant could emerge with high pandemic potential [156].…”

Influenza virus‐like particles harboring H9N2 HA and NA proteins induce a protective immune response in chicken

“…Furthermore, our study also showed that antigenic groups typically correspond with the phylogenetic relationships between viruses and that currently used commercial vaccine provides a reduced level of protection against more recent H9N2 strains. 17 Thus, this underlines the need for updating the vaccine used to give protection against current strains.…”

“…It has become predominant in vaccinated farm chickens in China, causing widespread influenza outbreaks before the H7N9 viruses emerged in humans; the latter viruses have inherited their internal genes from G57 genotype strains. In a previous study, the immunity efficacy of the currently used vaccine (A/chicken/shanghai/F/1998) against H9N2 has been evaluated and found unable to provide complete vaccine protection . Here, the HA and NA genes from a strain belonging to G57 genotype were used to construct a potential VLP‐based vaccine to protect against H9N2.…”

“…In a previous study, the immunity efficacy of the currently used vaccine (A/chicken/shanghai/F/1998) against H9N2 has been evaluated and found unable to provide complete vaccine protection. 17 Here, the HA and NA genes from a strain belonging to G57 genotype were used to construct a potential VLP-based vaccine to protect against H9N2.…”

Biological characterization of RNA polymerase proteins from human 2009 pandemic H1N1 and low pathogenic avian H5N2 and H9N2 influenza viruses

“…Iqbal et al discovered that the H9N2 viruses in the Indian sub-continent have extensive genetic reassortment, causing a novel genotype of H9N2 virus with NS gene similar to HPAI viruses, H7N3 and H5N1 (Iqbal et al, 2009). In addition, H9N2 viruses donated all six of reassortant's internal genes to novel H7N9 viruses, and facilitated the H7N9 virus formation by their genotypic evolution (Pu et al, 2015;Ge et al, 2016). The most recent study by Jia Wang and his group also highlighted the infectivity and interspecies transmission of enzootic H9N2 influenza viruses from birds to pigs (Wang et al, 2016a).…”