Human TRA2A determines influenza A virus-host adaptation by regulating viral mRNA splicing

Yinxing Zhu, Ruifang Wang, Luyao Yu, Huimin Sun, Shan Tian, Peng Li, Meilin Jin, Huanchun Chen, Wenjun Ma and Hongbo Zhou (2020)

Summarised by: Liping Wang.

Human TRA2A determines influenza A virus host adaptation by regulating viral mRNA splicing

Influenza viruses can quickly adapt and evade the host immune system, which has always been of great concern to prevent potential influenza outbreaks. To overcome this, in addition to studying the virus, scientists are also focusing on the host factors that are important for influenza virus replication. These include the exact virus-receptor recognition motifs that are involved in interaction which are crucial for the development of antiviral drugs against influenza virus.

A previous study described the interaction of the influenza virus neuraminidase protein (NP) with the host TRA2A: a protein involved in regulating pre-mRNA splicing, although the exact mechanism and downstream effects were yet unknown. To address this, in the current study, Zhu and colleagues demonstrate that the human host factor TRA2A inhibits avian influenza virus replication while promoting the replication of human influenza virus replication. The results are significant and point out that human factor TRA2A has opposite effects on human influenza virus and avian influenza virus replication in human cell culture. The study also shows that TRA2A can regulate the viral mRNA splicing by binding to the specific motif of viral mRNA identified by the group. The findings from this study uncover the adaptive mechanisms of avian influenza virus to human hosts and would contribute to developing related preventive strategies. Another possible application from these results would be mutating the TRA2A binding motif on the influenza virus to further attenuate the virus replication in cells for vaccine generation.