Metal–Protein Nanoparticles Facilitate Anti‐VSV and H1N1 Viruses Through the Coordinative Actions on Innate Immune Responses and METTL14

Abstract Host defense systems can invade viral infection through immune responses and cellular metabolism. Recently, many studies have shown that cellular metabolism can be reprogrammed through N 6 ‐methyladenosine (m 6 A) modifications during viral infection. Among of them, methyltransferase like‐14 enzyme (METTL14) plays an important role in m 6 A RNA modification, yet its antiviral function still remains unclear. In this work, it is uncovered that metal–protein nanoparticles designated GSTP1‐MT3(Fe 2+ ) (MPNP) can polarize macrophages toward the M1 phenotype and activate immune responses to induce Interferon‐beta (IFN‐β) production in vesicular stomatitis virus (VSV)‐infected macrophages. Further investigation elucidates that a high dose of IFN‐β can promote the expression of METTL14, which has a well anti‐VSV capacity. Moreover, it is found that other negative‐sense single‐stranded RNA viruses, such as influenza viruses (H1N1(WSN)), can also be inhibited through either immune responses or METTL14. Collectively, these findings provide insights into the antiviral function of METTL14 and suggest that the manipulation of METTL14 may be a potential strategy to intervene with other negative‐sense single‐stranded RNA viruses infections.