Vif 介导的 APOBEC3G 降解
中文名称
通路描述
HIV-1 辅助蛋白 Vif（病毒易感性因子）对于高效感染原代细胞群体（如淋巴细胞和巨噬细胞）以及'非耐受'细胞系是必需的。Vif 在产生细胞中中和宿主 DNA 编辑酶 APOBEC3G。事实上，在没有功能 Vif 的情况下，APOBEC3G 会选择性掺入 budding 的病毒颗粒，并在下一次感染循环中导致脱氧胞苷（dC）在逆转录过程中被去甲基化（Sheehy 等人，2003；Li 等人，2005；Stopak 等人，2003）。去甲基化将胞嘧啶转化为尿嘧啶，从而产生 G 到 A 转换和启动子中的终止密码子。在感染细胞中产生的异常 cDNA 要么以非功能性逆转录病毒的形式整合，要么被降解。Vif 通过与 APOBEC3G 直接结合并促进其泛素化，从而对抗 APOBEC3G 的抗病毒活性，将其招募到由 Cullin5、Rbx、ElonginC 和 ElonginB 组成的 E3 泛素酶复合物中，并通过 26S 蛋白酶体降解。因此，在 Vif 存在的情况下，APOBEC3G 掺入病毒颗粒的量极少。
英文描述
Vif-mediated degradation of APOBEC3G The HIV-1 accessory protein Vif (Viral infectivity factor) is required for the efficient infection of primary cell populations (e.g., lymphocytes and macrophages) and 'non-permissive' cell lines. Vif neutralises the host DNA editing enzyme, APOBEC3G, in the producer cell. Indeed, in the absence of a functional Vif, APOBEC3G is selectively incorporated into the budding virions and in the next cycle of infection leads to the deamination of deoxycytidines (dC) within the minus-strand cDNA during reverse transcription (Sheehy et al 2003; Li et al., 2005 ; Stopak et al. 2003).
Deamination changes cytidine to uracil and thus results in G to A transitions and stop codons in the provirus. The aberrant cDNAs produced in the infected cell can either be integrated in form of non-functional proviruses or degraded. Vif counteracts the antiviral activity of APOBEC3G by associating directly with it and promoting its polyubiquitination and degradation by the 26S proteasome.
Vif binds APOBEC3G and recruits it into an E3 ubiquitin-enzyme complex composed by the cytoplasmic proteins Cullin5, Rbx, ElonginC and ElonginB (Yu et al., 2003) . Thus, in the presence of Vif, APOBEC3G incorporation into the virion is minimal.
Deamination changes cytidine to uracil and thus results in G to A transitions and stop codons in the provirus. The aberrant cDNAs produced in the infected cell can either be integrated in form of non-functional proviruses or degraded. Vif counteracts the antiviral activity of APOBEC3G by associating directly with it and promoting its polyubiquitination and degradation by the 26S proteasome.
Vif binds APOBEC3G and recruits it into an E3 ubiquitin-enzyme complex composed by the cytoplasmic proteins Cullin5, Rbx, ElonginC and ElonginB (Yu et al., 2003) . Thus, in the presence of Vif, APOBEC3G incorporation into the virion is minimal.
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