Protein kinase C-delta regulates HIV-1 replication at an early post-entry step in macrophages.
Protein kinase C-delta regulates HIV-1 replication at an early post-entry step in macrophages.
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DOI：
10.1186/1742-4690-9-37
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发表时间：
2012-05-03
期刊：
影响因子：
3.3
通讯作者：
Bahraoui E
中科院分区：
文献类型：
--
作者：
Contreras X;Mzoughi O;Gaston F;Peterlin MB;Bahraoui E
巨噬细胞是CD 4和CCR 5阳性的，可以长时间维持HIV-1的复制。因此，这些细胞在病毒感染的传播、扩散和持续中起着关键作用。值得注意的是，目前的抗病毒疗法不能有效地靶向巨噬细胞。以前，已经证明CCR 5和gp 120之间的相互作用刺激PKC。然而，参与的PKC同工酶未被鉴定。在这项研究中，我们确定PKC-δ作为一个主要的细胞辅助因子的HIV-1复制在巨噬细胞。事实上，PKC-δ在病毒与其靶细胞之间的相互作用后被刺激。此外，抑制PKC-δ阻断了R5嗜性病毒在原代人巨噬细胞中的复制。然而，这种抑制对受体和共受体表达或融合没有显著影响。此外，它不影响含有R/U 5序列的早期逆转录产物的形成，但确实抑制了随后cDNA的合成。重要的是，PKC-δ的抑制改变了肌动蛋白的再分布，肌动蛋白是一种细胞辅因子，其完成逆转录的要求是以前建立的。它还阻止了逆转录复合物与细胞骨架的结合。这项工作强调了PKC-δ在人类巨噬细胞中HIV-1复制周期早期阶段的重要性。
Macrophages, which are CD4 and CCR5 positive, can sustain HIV-1 replication for long periods of time. Thus, these cells play critical roles in the transmission, dissemination and persistence of viral infection. Of note, current antiviral therapies do not target macrophages efficiently. Previously, it was demonstrated that interactions between CCR5 and gp120 stimulate PKC. However, the PKC isozymes involved were not identified. In this study, we identified PKC-delta as a major cellular cofactor for HIV-1 replication in macrophages. Indeed, PKC-delta was stimulated following the interaction between the virus and its target cell. Moreover, inhibition of PKC-delta blocked the replication of R5-tropic viruses in primary human macrophages. However, this inhibition did not have significant effects on receptor and co-receptor expression or fusion. Additionally, it did not affect the formation of the early reverse transcription product containing R/U5 sequences, but did inhibit the synthesis of subsequent cDNAs. Importantly, the inhibition of PKC-delta altered the redistribution of actin, a cellular cofactor whose requirement for the completion of reverse transcription was previously established. It also prevented the association of the reverse transcription complex with the cytoskeleton. This work highlights the importance of PKC-delta during early steps of the replicative cycle of HIV-1 in human macrophages.
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影响因子：
64.8
作者：
LAMPH, WW;WAMSLEY, P;VERMA, IM
通讯作者：
VERMA, IM
影响因子：
64.8
作者：
GUY, B;KIENY, MP;LECOCQ, JP
通讯作者：
LECOCQ, JP
影响因子：
82.9
作者：
Hirsch, VM;Sharkey, ME;Stevenson, M
通讯作者：
Stevenson, M
影响因子：
64.8
作者：
EMBRETSON, J;ZUPANCIC, M;HAASE, AT
通讯作者：
HAASE, AT
影响因子：
64.8
作者：
GRIFFIN, GE;LEUNG, K;NABEL, GJ
通讯作者：
NABEL, GJ