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Updated: Dec 17, 2025

Using Zebrafish Models of Human Influenza A Virus Infections to Screen Antiviral Drugs and Characterize Host Immune Cell Responses
Published on: January 20, 2017
Human TRA2A determines influenza A virus host adaptation by regulating viral mRNA splicing
Yinxing Zhu1,2, Ruifang Wang1,2, Luyao Yu1,2
1State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.
Abstract:
Several avian influenza A viruses (IAVs) have adapted to mammalian species, including humans. To date, the mechanisms enabling these host shifts remain incompletely understood. Here, we show that a host factor, human TRA2A (huTRA2A), inhibits avian IAV replication, but benefits human IAV replication by altered regulation of viral messenger RNA (mRNA) splicing. huTRA2A depresses mRNA splicing by binding to the intronic splicing silencer motif in the M mRNA of representative avian YS/H5N1 or in the NS mRNA of representative human PR8/H1N1 virus, leading to completely opposite effects on replication of the human and avian viruses in vitro and in vivo. We also confirm that the M-334 site and NS-234/236 sites are critical for TRA2A binding, mRNA splicing, viral replication, and pathogenicity. Our results reveal the underlying mechanisms of adaptation of avian influenza virus to human hosts, and suggest rational strategies to protect public health.
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