Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, 2 Wanglang Road, Bangkoknoi, Bangkok 10700, Thailand.
Princess Srisavangavadhana College of Medicine, Chulabhorn Royal Academy, Thailand.
Virus Res. 2023 Sep;334:199162. doi: 10.1016/j.virusres.2023.199162. Epub 2023 Jun 26.
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.
SLFN 蛋白是干扰素刺激的早期反应基因的一个亚类，具有抗病毒特性。先前在感染人类免疫缺陷病毒 1（HIV-1）的细胞中证明了 SLFN11 的抗病毒机制，并且表明 SLFN11 以密码子使用特异性方式抑制 HIV-1 病毒的产生。许多病毒的密码子使用模式与宿主的密码子使用模式有很大不同。SLFN11 对 HIV-1 表达的密码子使用特异性抑制表明，SLFN11 可能能够抑制其他密码子使用模式不佳的病毒。然而，SLFN11 对甲型流感病毒（IAV）复制的影响从未被报道过。在 IAV 感染时观察到 SLFN11 表达的诱导。降低 SLFN11 的表达也促进了流感病毒的复制。此外，我们发现过表达 SLFN11 可以降低具有病毒密码子使用模式的报告基因的表达，并且对病毒血凝素（HA）基因的抑制是密码子特异性的，因为优化的密码子 HA 的表达不受影响。这些结果表明，SLFN11 以密码子使用特异性方式抑制甲型流感病毒，并且 SLFN11 可能有助于对甲型流感病毒的先天防御。
