Huthoff Hendrik, Towers Greg J
Department of Infectious Diseases, Guy's, King's and St Thomas' School of Medicine, London SE1 9RT, UK.
Trends Microbiol. 2008 Dec;16(12):612-9. doi: 10.1016/j.tim.2008.08.013. Epub 2008 Oct 29.
Pathogenic viral infections have exerted selection pressure on their hosts to evolve cellular antiviral inhibitors referred to as restriction factors. Examples of such molecules are APOBEC3G, APOBEC3F and TRIM5alpha. APOBEC3G and APOBEC3F are cytidine deaminases that are able to strongly inhibit retroviral replication by at least two mechanisms. They are counteracted by the lentiviral Vif protein. TRIM5alpha binds to sensitive, incoming retroviruses via its C-terminal PRY/SPRY domain and rapidly recruits them to the proteasome before significant viral DNA synthesis can occur. Both of these proteins robustly block retroviral replication in a species-specific way. It remains an open but important question as to whether innate restriction factors such as these can be harnessed to inhibit HIV-1 replication in humans.
致病性病毒感染对其宿主施加了选择压力，促使宿主进化出被称为限制因子的细胞抗病毒抑制剂。这类分子的例子有载脂蛋白B mRNA编辑酶催化多肽样蛋白3G（APOBEC3G）、载脂蛋白B mRNA编辑酶催化多肽样蛋白3F（APOBEC3F）和TRIM5α。APOBEC3G和APOBEC3F是胞苷脱氨酶，它们能够通过至少两种机制强烈抑制逆转录病毒复制。它们会被慢病毒Vif蛋白抵消。TRIM5α通过其C端PRY/SPRY结构域与敏感的入侵逆转录病毒结合，并在病毒DNA大量合成之前迅速将它们招募到蛋白酶体。这两种蛋白质都以物种特异性的方式强力阻断逆转录病毒复制。像这样的先天限制因子是否能够用于抑制人类体内的HIV-1复制，这仍然是一个悬而未决但很重要的问题。
