A TRIM5 α-independent post-entry restriction to HIV-1 infection of macaque cells that is dependent on the path of entry
A TRIM5 α-independent post-entry restriction to HIV-1 infection of macaque cells that is dependent on the path of entry
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DOI：
10.1016/j.virol.2007.02.002
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发表时间：
2007-07-05
期刊：
影响因子：
3.7
通讯作者：
Overbaugh, Julie
中科院分区：
文献类型：
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作者：
Pineda, Mario Javier;Orton, Brannon R.;Overbaugh, Julie
人类免疫缺陷1型（HIV-1）的复制在猕猴细胞中受到限制，部分原因是宿主因素在进入后提供内在免疫。在这里，我们表明，恒河猴上皮细胞系工程表达人CD 4，sMAG 1细胞，有至少两个进入后限制HIV-1复制：一个是依赖于先前描述的进入后限制因子的猕猴细胞，TRIM 5 α，另一个主要是TRIM 5 α-in依赖。用具有用VSV-G包膜假型化的HIV-I核心的颗粒观察到的TRIM 5 α限制是可饱和的，并且可以通过将TRIM 5 α特异性siRNA引入细胞中而完全消除。当用R5-HIV-1感染表达人CCR 5的sMAG 1细胞时，观察到类似的TRIM 5a依赖性限制。相反，即使当病毒以足以使TRIM 5a饱和的水平使用CD 4和内源性恒河猴共受体进入sMAGI细胞时，它们也不会有效地感染sMAGI细胞。用TRIM 5 α特异性siRNA处理sMAGI细胞也不能缓解这种进入后限制;无论HIV-1核心是用SIV包膜还是R5-HIV-1包膜假型化，这都是正确的。总之，这些数据表明，有一个替代的复制限制，这里称为Lv 3，这是遇到的病毒，通过与CD 4和内源性恒河猴共受体的相互作用进入。因此，这些发现表明，进入后事件取决于HIV-1进入细胞的机制。(C)2007爱思唯尔公司All rights reserved.
The replication of human immunodeficiency type-1 (HIV-1) is restricted in macaque cells, in part due to host factors that provide intrinsic immunity after entry. Here we show that a rhesus macaque epithelial cell line engineered to express human CD4, sMAGI cells, has at least two post-entry restrictions to HIV-1 replication: one that is dependent on a previously described post-entry restriction factor of macaque cells, TRIM5 alpha, and another that is primarily T RIM5 alpha-i n dependent. The TRIM5 alpha restriction, which was observed with particles that had an HIV- I core pseudotyped with VSV-G envelope, is saturable and can be completely abrogated by introducing TRIM5 a -specific siRNA into the cells. A similar TRIM 5 a-dependent restriction was observed when sMAGI cells expressing human CCR5 were infected with an R5-HIV-1. In contrast, even when viruses enter sMAGI cells using CD4 and an endogenous rhesus coreceptor at levels sufficient to saturate TRIM5a, they do not productively infect the sMAGI cells. Nor does treatment of sMAGI cells with TRIM5 alpha-specific siRNA relieve this post-entry restriction; this was true whether the HIV-1 core was pseudotyped with SIV envelope or an R5-HIV-1 envelope. Together these data suggest that there is an alternate restriction to replication, here called Lv3, that is encountered by viruses that enter via interaction with CD4 and an endogenous rhesus coreceptor. Thus, these findings suggest that post-entry events are dependent upon the mechanism by which HIV-1 enters the cell. (C) 2007 Elsevier Inc. All rights reserved.