Selenoprotein M Inhibits the Replication of Influenza A Virus by Regulating Reactive Oxygen Species Levels

Background: Influenza A virus (IAV) is the major pathogen responsible for influenza pandemics and can cause seasonal influenza outbreaks. In general, viral infection of host cells increases reactive oxygen species (ROS) levels, a process that triggers cell death, lung injury (LI), and other damage mechanisms. Methods: In our previous study, we revealed that selenoproteins may inhibit IAV replication at the cellular level. In this study, we determined the effect of selenoprotein M (SelM) on Nanoluc-IAV-PR8 replication through Nanoluc analysis. The mechanism through which selenoprotein inhibits the replication of the influenza virus was investigated using the SelM knockout cell line, nano-luciferase reporter assays, RNAi, qPCR, Western blot, and confocal microscopy. Results: Our experimental results show that SelM can effectively inhibit the replication of influenza A viruses and could potentially be used as a broad-spectrum inhibitor for IAV therapy in future clinical treatments. The increase in ROS levels induced by IAV infection was found to be inhibited by SelM, which possesses an important Sec functional site, thus weakening the ability of IAV to replicate in cells. Conclusions: The results of this study highlight SelM as a selenoprotein that can effectively inhibit IAV replication.