Vpr.A3A chimera inhibits HIV replication
Vpr.A3A chimera inhibits HIV replication
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DOI：
10.1074/jbc.m706436200
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发表时间：
2008-02-01
影响因子：
4.8
通讯作者：
Peterlin, B. Matija
中科院分区：
文献类型：
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作者：
Aguiar, Renato S.;Lovsin, Nika;Peterlin, B. Matija
几种APOBEC3蛋白（A3F和A3G）是胞苷脱氨酶，在缺乏病毒感染因子（Vif）蛋白的情况下限制人类免疫缺陷病毒（HIV）的复制。然而，Vif导致其退化并抵消其影响。另一个成员A3A限制一些反转录转座子和另一种病毒，但不限制HIV。我们认为，这一失败是由于缺乏适当的目标。因此，我们将A3A与另一种病毒蛋白Vpr融合，Vpr结合Gag中的p6并掺入病毒核心。事实上，Vpr。在病毒核心中发现大量的A3A嵌合体，而不是A3A。它还有效地限制了HIV和猴免疫缺陷病毒在存在和不存在Vif的情况下的复制。因为我们在病毒cDNA中发现了高频率的G到A突变，这种抗病毒活性是由DNA编辑介导的。有趣的是，我们的融合蛋白不限制鼠白血病病毒，其不包含Vpr。因此，通过适当地靶向有效的单域胞苷脱氨酶，我们使HIV和猿免疫缺陷病毒限制性耐Vif。
Several APOBEC3 proteins (A3F and A3G), that are cytidine deaminases restrict human immunodeficiency virus (HIV) replication in the absence of the viral infectivity factor (Vif) protein. However, Vif leads to their degradation and counteracts their effects. Another member, A3A, restricts some retrotransposons and another virus but not HIV. Wereasoned that this failure was due to the lack of appropriate targeting. Thus, we fused A3A to another viral protein, Vpr, which binds p6 in Gag and is incorporated into viral cores. Indeed, the Vpr. A3A chimera but not A3A was found abundantly in the viral core. It also restricted potently the replication of HIV and simian immunodeficiency virus in the presence and absence of Vif. Because we identified a high frequency of G to Amutations in viral cDNAs, this antiviral activity was mediated by DNA editing. Interestingly, our fusion protein did not restrict murine leukemia virus, which does not incorporate Vpr. Thus, by targeting appropriately a potent single domain cytidine deaminase, we rendered HIV and simian immunodeficiency virus restriction resistant to Vif.