HIV-1 replication and APOBEC3 antiviral activity are not regulated by P bodies.
HIV-1 replication and APOBEC3 antiviral activity are not regulated by P bodies.
复制标题
HIV-1 复制和 APOBEC3 抗病毒活性不受 P 体调节。
DOI：
10.1128/jvi.00595-12
复制
发表时间：
2012
影响因子：
5.4
通讯作者：
Malim,MichaelH
中科院分区：
文献类型：
--
作者：
Phalora,PrabhjeetK;Sherer,NathanM;Wolinsky,StevenM;Swanson,ChadM;Malim,MichaelH
APOBEC 3胞苷脱氨酶在宿主介导的防御外源性病毒，最显著的是人类免疫缺陷病毒1型（HIV-1）和内源性转座因子中起关键作用。APOBEC 3G和APOBEC 3F与许多调节细胞RNA代谢的蛋白质相互作用，包括RNA诱导沉默复合物（RISC）的组分，并与这些蛋白质的子集共定位于mRNA加工体（P体），这是mRNA翻译抑制和衰变的位点。我们试图确定P体和相关蛋白在HIV-1复制和APOBEC 3抗病毒活性中的作用。虽然我们建立了APOBEC 3蛋白掺入病毒体和定位于P体之间的正相关性，但P体组分DDX 6或Lsm 1的消耗不影响HIV-1复制、APOBEC 3包装入病毒体或APOBEC 3蛋白介导的HIV-1感染性抑制。此外，HIV-1基因组RNA和Gag均不与P体蛋白共定位。然而，同时消耗多个Argonaute家族成员（RISC的效应蛋白）可能会适度增加病毒感染性。由于一些APOBEC 3蛋白与几种Argonaute蛋白相互作用，我们还测试了它们是否可以调节microRNA（miRNA）活性。我们没有发现APOBEC 3蛋白特异性调节miRNA功能的证据，尽管观察到对转染基因表达的更普遍的影响。总之，我们的研究结果表明，P体和某些相关蛋白不调节HIV-1复制或APOBEC 3蛋白的抗病毒活性。因此，定位于P体可能提供了一种将APOBEC 3酶活性从细胞DNA中分离出来的方法，或者可能与尚未鉴定的细胞功能有关。
The APOBEC3 cytidine deaminases play a critical role in host-mediated defense against exogenous viruses, most notably, human immunodeficiency virus type-1 (HIV-1) and endogenous transposable elements. APOBEC3G and APOBEC3F interact with numerous proteins that regulate cellular RNA metabolism, including components of the RNA-induced silencing complex (RISC), and colocalize with a subset of these proteins to mRNA processing bodies (P bodies), which are sites of mRNA translational repression and decay. We sought to determine the role of P bodies and associated proteins in HIV-1 replication and APOBEC3 antiviral activity. While we established a positive correlation between APOBEC3 protein incorporation into virions and localization to P bodies, depletion of the P-body components DDX6 or Lsm1 did not affect HIV-1 replication, APOBEC3 packaging into virions or APOBEC3 protein mediated inhibition of HIV-1 infectivity. In addition, neither HIV-1 genomic RNA nor Gag colocalized with P-body proteins. However, simultaneous depletion of multiple Argonaute family members, the effector proteins of RISC, could modestly increase viral infectivity. Because some APOBEC3 proteins interact with several Argonaute proteins, we also tested whether they could modulate microRNA (miRNA) activity. We found no evidence for the specific regulation of miRNA function by the APOBEC3 proteins, though more general effects on transfected gene expression were observed. In sum, our results indicate that P bodies and certain associated proteins do not regulate HIV-1 replication or APOBEC3 protein antiviral activity. Localization to P bodies may therefore provide a means of sequestering APOBEC3 enzymatic activity away from cellular DNA or may be linked to as yet unidentified cellular functions.