Novel host factors associated with resistance to highly pathogenic avian influenza in wild birds inferred from primary cell culture

Bird species differ in the sensitivity to the highly pathogenic avian influenza virus (HPAIV). Here, we infected fibroblasts from 11 bird species with the H5N1 HPAIV strain A/chicken/Yamaguchi/7/2004. These species were categorized into three groups based on previous studies: HPAI-resistant (rock pigeon, hooded crane, white-necked crane, and Japanese crane), HPAI- susceptible (chicken, mountain hawk-eagle, northern goshawk, peregrine falcon, and golden eagle), and those with unknown susceptibility to HPAI (Okinawa rail and Japanese white stork). We performed gene expression analysis to identify genes uniquely upregulated in the HPAI-resistant species and determine genetic markers of HPAIV susceptibility. We found that two genes involved in antiviral response: OAS and IFIT5 expression levels were commonly upregulated after infection in the HPAI-resistant species, but not in the HPAI- susceptible species or species with unknown sensitivity to HPAI. In addition, upregulation ratios of OAS expression at 6 h post-infection and of OAS and IFIT5 at 12 h post-infection were significantly higher in the resistant species than in the susceptible species. We conclude that IFIT5 and OAS could be genetic markers for HPAIV susceptibility, and that Okinawa rail and Japanese white stork are likely susceptible to HPAIV, indicating the need for their conservation and protection against HPAIV infection.