Schlafen (SLFN) proteins are a subset of interferon-stimulated early response genes with antiviral properties. An antiviral mechanism of SLFN11 was previously demonstrated in human immunodeficiency virus type 1 (HIV-1)-infected cells, and it was shown that SLFN11 inhibited HIV-1 virus production in a codon usage-specific manner. The codon usage patterns of many viruses are vastly different from those of their hosts. The codon usage-specific inhibition of HIV-1 expression by SLFN11 suggests that SLFN11 may be able to inhibit other viruses with a suboptimal codon usage pattern. However, the effect of SLFN11 on the replication of influenza A virus (IAV) has never been reported. The induction of SLFN11 expression was observed upon IAV infection. The reduction of SLFN11 expression also promotes influenza virus replication. Moreover, we found that overexpression of SLFN11 could reduce the expression of a reporter gene with a viral codon usage pattern, and the inhibition of viral hemagglutinin (HA) gene was codon-specific as the expression of codon optimized HA was not affected. These results indicate that SLFN11 inhibits the influenza A virus in a codon-specific manner and that SLFN11 may contribute to innate defense against influenza A viruses.
Copyright © 2023. Published by Elsevier B.V.