A novel envelope mediated post entry restriction of murine leukaemia virus in human cells is Ref1/TRIM5α independent.
A novel envelope mediated post entry restriction of murine leukaemia virus in human cells is Ref1/TRIM5α independent.
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DOI：
10.1186/1742-4690-7-81
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发表时间：
2010-10-07
期刊：
影响因子：
3.3
通讯作者：
McKnight Á
中科院分区：
文献类型：
--
作者：
Oliveira NM;Trikha R;McKnight Á
对逆转录病毒感染的“内在”抗性首先被Friend病毒易感基因（Fv 1）识别，该基因决定了不同鼠种对鼠白血病病毒（MLV）感染的易感性。类似地，蛋白质的三重基序（TRIM）家族以灵长类宿主物种特异性方式决定慢病毒限制。例如，恒河猴TRIM 5 α（rhTRIM 5 α）可以有效限制HIV-1感染，而人TRIM 5 α（huTRIM 5 α）仅对SIVmac和HIV-1感染性（Lv 1）有轻微影响。人TRIM 5 α能够限制MLV-N病毒复制，但对MLV-B或MLV-NB病毒感染无效。一些HIV-2病毒的Lv 2限制在人类细胞中可见。与Lv 1一样，Lv 2是一种进入后限制因子，其病毒决定簇已定位于病毒衣壳（CA）。然而，与Lv 1不同，Lv 2除了CA之外还由包络（Env）确定。在这里，我们提出了一种新的Env确定的进入后限制假型MLV-B和MLV-NB核心的人细胞中的感染的证据。我们在含有绿色荧光蛋白（GFP）报告基因的MLV-B和-NB CA上产生了用各种γ和慢病毒Env假型化的逆转录病毒载体。流式细胞术用于测定NP 2/CD 4/CXCR 4（用HIV受体稳定转导的胶质瘤细胞系）和HeLa/CD 4细胞系中的转导效率。与NP 2/CD 4/CXCR 4细胞相比，HeLa/CD 4细胞系以Env依赖性方式限制两种MLV CA。逆转录（RT）转录本的定量聚合酶链反应（QT-PCR）分析表明，这种限制发生在进入后和RT水平。huTRIM 5 α的siRNA敲除排除了该细胞组分在介导该限制中的直接作用。我们描述了一个以前未观察到的Env确定的限制MLV-B和MLV-NB CA在HeLa/CD 4细胞时，假型与HIV-2和RD 114 Env，但不是巨猿白血病病毒（GALV），HIV-1或Amphotrophic（Ampho）Env。我们的数据进一步证明了Env和CA介导的对进入后宿主细胞限制的易感性的可变性。我们讨论了这些发现的相关性，越来越多的证据支持先天性宿主免疫逆转录病毒感染的复杂性。
'Intrinsic' resistance to retroviral infection was first recognised with the Friend virus susceptibility gene (Fv1), which determines susceptibility to murine leukaemia virus (MLV) infection in different murine species. Similarly, the tripartite motif (TRIM) family of proteins determine lentiviral restriction in a primate host-species specific manner. For example rhesus TRIM5α (rhTRIM5α) can potently restrict HIV-1 infection while human TRIM5α (huTRIM5α) only has a mild effect on SIVmac and HIV-1 infectivity (Lv1). Human TRIM5α is able to restrict MLV-N virus replication, but is ineffective against MLV-B or MLV-NB virus infection. Lv2 restriction of some HIV-2 viruses is seen in human cells. Like Lv1, Lv2 is a post-entry restriction factor, whose viral determinants have been mapped to the viral capsid (CA). Unlike Lv1, however, Lv2 is determined by envelope (Env) in addition to CA. Here we present evidence of a novel Env determined post entry restriction to infection in human cells of pseudotyped MLV-B and MLV-NB cores. We generated retroviral vectors pseudotyped with various gamma and lentiviral Envs on MLV-B and -NB CAs containing a green fluorescent protein (GFP) reporter. Flow cytometry was used to determine transduction efficiencies in NP2/CD4/CXCR4 (glioma cell line stably transduced with the HIV receptors) and HeLa/CD4 cell lines. The HeLa/CD4 cell line restricted both MLV CAs in an Env dependent manner, compared to NP2/CD4/CXCR4 cells. Quantitative polymerase chain reaction (QT-PCR) analysis of reverse transcription (RT) transcripts demonstrates that this restriction occurs at a post entry and RT level. siRNA knockdown of huTRIM5α ruled out a direct role for this cellular component in mediating this restriction. We describe a previously unobserved Env determined restriction of MLV-B and MLV-NB CAs in HeLa/CD4 cells when pseudotyped with HIV-2 and RD114 Envs, but not gibbon ape leukaemia virus (GALV), HIV-1 or Amphotrophic (Ampho) Envs. Our data further demonstrate the variability of Env and CA mediated susceptibility to post entry host cell restriction. We discuss the relevance of these findings in light of the growing evidence supporting the complexities involved in innate host immunity to retroviral infection.
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影响因子：
64.8
作者：
Best, S;LeTissier, P;Stoye, JP
通讯作者：
Stoye, JP
DOI：
10.1073/pnas.91.1.78
发表时间：
1994-01-04
影响因子：
11.1
作者：
MILLER, DG;EDWARDS, RH;MILLER, AD
通讯作者：
MILLER, AD
影响因子：
3.7
作者：
Pineda, Mario Javier;Orton, Brannon R.;Overbaugh, Julie
通讯作者：
Overbaugh, Julie
影响因子：
3.7
作者：
Diaz-Griffero, Felipe;Perron, Michel;Sodroski, Joseph
通讯作者：
Sodroski, Joseph
影响因子：
5.4
作者：
Lassaux, A;Sitbon, M;Battini, JL
通讯作者：
Battini, JL