Takeuchi Hiroaki, Kao Sandra, Miyagi Eri, Khan Mohammad A, Buckler-White Alicia, Plishka Ron, Strebel Klaus
Laboratory of Molecular Microbiology, NIAID, National Institutes of Health, Bethesda, Maryland 20892-0460, USA.
J Biol Chem. 2005 Jan 7;280(1):375-82. doi: 10.1074/jbc.M408987200. Epub 2004 Nov 3.
The virus infectivity factor (Vif) is a protein encoded by most primate lentiviruses. Recent evidence suggests that HIV-1 Vif reduces the intracellular levels of the host cytidine deaminase APOBEC3G (Apo3G) and inhibits its packaging into virions. These functions of Vif are thought to be species-specific. Accordingly, HIV-1 Vif can target only human Apo3G (hApo3G), whereas, African green monkey simian immunodeficiency virus (SIVagm) Vif can inhibit African green monkey but not human Apo3G. Consistent with this, we found that SIVagm Vif does not affect the stability of exogenously and endogenously expressed hApo3G and does not prevent packaging of exogenous and endogenous hApo3G into SIVagm virions. Nevertheless, SIVagm Vif supported spreading infection of SIVagm virus in the hApo3G-positive human A3.01 T cell line and rescued infectivity of viruses produced from Apo3G-expressing HeLa cells. Sequence analysis verified that SIVagm Vif inhibited the accumulation of hApo3G-induced mutations, suggesting that SIVagm Vif is indeed active in human cells. Our data suggest that SIVagm Vif can inhibit hApo3G activity without inducing its intracellular degradation or preventing its packaging into virions.
病毒感染性因子（Vif）是大多数灵长类慢病毒编码的一种蛋白质。最近的证据表明，HIV-1 Vif可降低宿主胞苷脱氨酶载脂蛋白B mRNA编辑酶催化多肽样3G（APOBEC3G，Apo3G）的细胞内水平，并抑制其包装进病毒颗粒。Vif的这些功能被认为具有物种特异性。因此，HIV-1 Vif只能靶向人类Apo3G（hApo3G），而非洲绿猴猿猴免疫缺陷病毒（SIVagm）的Vif能抑制非洲绿猴的Apo3G，但不能抑制人类的Apo3G。与此一致的是，我们发现SIVagm Vif不影响外源性和内源性表达的hApo3G的稳定性，也不阻止外源性和内源性hApo3G包装进SIVagm病毒颗粒。然而，SIVagm Vif支持SIVagm病毒在hApo3G阳性的人A3.01 T细胞系中传播感染，并拯救了从表达Apo3G的HeLa细胞产生的病毒的感染性。序列分析证实，SIVagm Vif抑制了hApo3G诱导的突变的积累，这表明SIVagm Vif在人类细胞中确实具有活性。我们的数据表明，SIVagm Vif可以抑制hApo3G的活性，而不诱导其在细胞内降解或阻止其包装进病毒颗粒。
