Characteristics of Avian Influenza H9N2 Virus Isolated from Humans and its Seroprevalence Among Occupationally Exposed Populations in China

Abstract Background: The first human-infected H9N2 influenza case can be traced back to 1998. Although the H9N2 influenza virus has low pathogenicity in animals, it donated partial or whole cassettes of internal genes to reassort novel viruses, such as H7N9, H10N8 and H5N6 viruses, that caused human infections with high fatality. Since 2013, sporadic but increasingly frequent human cases caused by H9N2 influenza virus have been confirmed globally, and most of them were from China. Methods: Information on human infections with H9N2 influenza virus was collected. Viral molecular determinants were determined by deep sequencing, and phylogenetic analysis was performed using MEGA 6.06. Antigenic analysis was performed by a hemagglutination inhibition (HI) assay. Receptor binding preference analysis was conducted based on a solid-phase binding assay with synthetic sialylglycopolymers. Antiviral susceptibility was determined by a fluorescence-based neuraminidase (NA) inhibition assay. Serological study of occupationally exposed populations was performed by HI assay screening and confirmed by microneutralization assay.Results: From 2013 to 2018, 33 human H9N2cases were reported in China, among them 75.7% were children under 10 years old .The 22 viruses were isolated and concentrated in the Y280/G9 lineage of the HA and NA genes. All human H9N2 viruses belonged to the Y280/G9 antigenic lineage, presented a human-like receptor binding preference and remained susceptible to NA inhibitors, but most demonstrated resistance to M2 inhibitors. The seroprevalence of occupationally exposed populations was 2.15%, 3.17%, 2.93% and 1.54% from 2015 to 2018, respectively. A significant difference in seroprevalence was shown between provinces with human cases (3.66%) and provinces without human cases (2.18%). Conclusions: The continuous antigenic drift and human-like receptor binding preference of the H9N2 virus enable it to have a high risk of causing human infections. The status of the seropositivity in occupationally exposed populations implies a substantial threat to public health. Research on human infection with H9N2 influenza virus should be strengthened to monitor the emergence of sustainable human-to-human transmission and the possibility of an endemic or a pandemic related to it.