Key Laboratory of Molecular Microbiology and Biotechnology (Ministry of Education) and Key Laboratory of Microbial Functional Genomics (Tianjin), College of Life Sciences, Nankai University, Tianjin, China.
Key Laboratory of Molecular Microbiology and Biotechnology (Ministry of Education) and Key Laboratory of Microbial Functional Genomics (Tianjin), College of Life Sciences, Nankai University, Tianjin, China.
Virology. 2021 Mar;555:78-88. doi: 10.1016/j.virol.2020.12.015. Epub 2020 Dec 29.
Recently, the Schlafen (SLFN) proteins have been identified as a novel interferon-stimulated family with antiviral properties. In this study, we reported that SLFN11 inhibited prototype foamy virus (PFV) replication. Over-expression of human SLFN11 reduced viral production, while knockdown of SLFN11 enhanced viral infectivity. In addition, SLFN11 from cattle and African green monkey also suppressed PFV production. Both the ATPase activity and helicase activity of SLFN11 were required for its inhibitory function. Dephosphorylation activated the antiviral activity of SLFN11. More importantly, SLFN11 inhibited the expression of viral protein, which was rescued by viral gene codon optimization. Together, our results demonstrated that SLFN11 impaired PFV viral protein synthesis by exploiting the distinct codon usage between the virus and the host. These findings further broaden our understanding of the antiviral properties of the SLFN family and the molecular mechanism of PFV latent infection.
最近，Schlafen（SLFN）蛋白被鉴定为具有抗病毒特性的干扰素刺激家族的新成员。在这项研究中，我们报告了 SLFN11 抑制原型泡沫病毒（PFV）复制。人 SLFN11 的过表达降低了病毒的产生，而 SLFN11 的敲低增强了病毒的感染力。此外，牛和非洲绿猴的 SLFN11 也抑制了 PFV 的产生。SLFN11 的 ATP 酶活性和解旋酶活性均对其抑制功能至关重要。去磷酸化激活了 SLFN11 的抗病毒活性。更重要的是，SLFN11 通过利用病毒和宿主之间不同的密码子使用来抑制病毒蛋白的表达，这种抑制作用可以被病毒基因密码子优化所挽救。总之，我们的研究结果表明，SLFN11 通过利用病毒和宿主之间不同的密码子使用来破坏 PFV 病毒蛋白的合成，从而抑制 PFV 的复制。这些发现进一步拓宽了我们对 SLFN 家族抗病毒特性以及 PFV 潜伏感染分子机制的理解。
