Murrell Ben, Vollbrecht Thomas, Guatelli John, Wertheim Joel O
Department of Medicine, University of California, San Diego, San Diego, California, USA.
Department of Medicine, University of California, San Diego, San Diego, California, USA San Diego Veterans Affairs Healthcare System, La Jolla, California, USA.
J Virol. 2016 Aug 26;90(18):8085-9. doi: 10.1128/JVI.00972-16. Print 2016 Sep 15.
Molecular evolutionary arms races between viruses and their hosts are important drivers of adaptation. These Red Queen dynamics have been frequently observed in primate retroviruses and their antagonists, host restriction factor genes, such as APOBEC3F/G, TRIM5-α, SAMHD1, and BST-2. Host restriction factors have experienced some of the most intense and pervasive adaptive evolution documented in primates. Recently, two novel host factors, SERINC3 and SERINC5, were identified as the targets of HIV-1 Nef, a protein crucial for the optimal infectivity of virus particles. Here, we compared the evolutionary fingerprints of SERINC3 and SERINC5 to those of other primate restriction factors and to a set of other genes with diverse functions. SERINC genes evolved in a manner distinct from the canonical arms race dynamics seen in the other restriction factors. Despite their antiviral activity against HIV-1 and other retroviruses, SERINC3 and SERINC5 have a relatively uneventful evolutionary history in primates.
Restriction factors are host proteins that block viral infection and replication. Many viruses, like HIV-1 and related retroviruses, evolved accessory proteins to counteract these restriction factors. The importance of these interactions is evidenced by the intense adaptive selection pressures that dominate the evolutionary histories of both the host and viral genes involved in this so-called arms race. The dynamics of these arms races can point to mechanisms by which these viral infections can be prevented. Two human genes, SERINC3 and SERINC5, were recently identified as targets of an HIV-1 accessory protein important for viral infectivity. Unexpectedly, we found that these SERINC genes, unlike other host restriction factor genes, show no evidence of a recent evolutionary arms race with viral pathogens.
病毒与其宿主之间的分子进化军备竞赛是适应性的重要驱动因素。这些红皇后动态在灵长类逆转录病毒及其拮抗剂、宿主限制因子基因（如载脂蛋白B mRNA编辑酶催化多肽样3F/G、三结构域蛋白5-α、SAM域和HD结构域包含蛋白1以及骨髓基质抗原2）中经常被观察到。宿主限制因子经历了灵长类动物中记录的一些最强烈和普遍的适应性进化。最近，两个新的宿主因子丝氨酸整合蛋白3（SERINC3）和丝氨酸整合蛋白5（SERINC5）被确定为HIV-1 Nef的靶点，HIV-1 Nef是一种对病毒颗粒最佳感染性至关重要的蛋白质。在这里，我们将SERINC3和SERINC5的进化特征与其他灵长类限制因子以及一组具有不同功能的其他基因的进化特征进行了比较。SERINC基因的进化方式与其他限制因子中常见的典型军备竞赛动态不同。尽管SERINC3和SERINC5对HIV-1和其他逆转录病毒具有抗病毒活性，但它们在灵长类动物中的进化历史相对平稳。
限制因子是阻止病毒感染和复制的宿主蛋白。许多病毒，如HIV-1和相关逆转录病毒，进化出辅助蛋白来对抗这些限制因子。这些相互作用的重要性体现在强烈的适应性选择压力上，这些压力主导了参与这场所谓军备竞赛的宿主和病毒基因的进化历史。这些军备竞赛的动态可以指向预防这些病毒感染的机制。最近，两个人类基因SERINC3和SERINC5被确定为对病毒感染性很重要的HIV-1辅助蛋白的靶点。出乎意料的是，我们发现这些SERINC基因与其他宿主限制因子基因不同，没有显示出最近与病毒病原体进行进化军备竞赛的证据。
