The interferon response inhibits HIV particle production by induction of TRIM22.
The interferon response inhibits HIV particle production by induction of TRIM22.
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DOI：
10.1371/journal.ppat.1000007
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发表时间：
2008-02-29
期刊：
影响因子：
6.7
通讯作者：
Bushman FD
中科院分区：
文献类型：
--
作者：
Barr SD;Smiley JR;Bushman FD
用1型干扰素处理人类细胞限制HIV复制。在这里，我们报告，三方基序蛋白TRIM 22是一个关键的调解人。我们使用转录谱来鉴定干扰素治疗诱导的细胞基因，并将TRIM 22鉴定为最强烈上调的基因之一。与之前的研究一样，我们证实TRIM 22过表达抑制了HIV复制。为了评估自然诱导条件下表达的TRIM 22的作用，我们使用RNAi比较了干扰素在TRIM 22缺失细胞中的作用，发现HIV颗粒释放在敲除中显着增加，这意味着TRIM 22充当天然的抗病毒效应子。进一步的研究表明，TRIM 22抑制仅含有Gag的病毒样颗粒的出芽，表明Gag是TRIM 22的靶标。TRIM 22不阻断MLV或EIAV Gag颗粒的释放。抑制作用与HIV Gag的弥散性细胞质染色有关，而不是在质膜上的积累，表明TRIM 22破坏了适当的运输。TRIM 22的突变分析表明，催化氨基酸Cys 15和Cys 18的RING结构域所需的TRIM 22的抗病毒活性。这些数据揭示了1型干扰素阻碍HIV复制的途径。干扰素由细胞响应外来病原体如病毒的攻击而产生。I型干扰素（例如，IFNβ）抑制HIV-1复制的作用尚未完全阐明。我们鉴定了一个被称为TRIM 22的基因，该基因属于三部分基序（TRIM）家族，该家族被IFNβ强烈诱导。使用RNA干扰来降低TRIM 22的表达，我们表明TRIM 22在天然水平表达时是IFNβ应答的关键介导物。我们证明，TRIM 22阻断了病毒结构蛋白Gag向细胞表面的细胞内运输，并且TRIM 22的抗病毒活性依赖于两个半胱氨酸残基（Cys 15和Cys 18），这两个半胱氨酸残基对含RING蛋白的E3连接酶活性至关重要。本报告描述了一种机制，其中I型干扰素阻断HIV-1复制。
Treatment of human cells with Type 1 interferons restricts HIV replication. Here we report that the tripartite motif protein TRIM22 is a key mediator. We used transcriptional profiling to identify cellular genes that were induced by interferon treatment and identified TRIM22 as one of the most strongly up-regulated genes. We confirmed, as in previous studies, that TRIM22 over-expression inhibited HIV replication. To assess the role of TRIM22 expressed under natural inducing conditions, we compared the effects of interferon in cells depleted for TRIM22 using RNAi and found that HIV particle release was significantly increased in the knockdown, implying that TRIM22 acts as a natural antiviral effector. Further studies showed that TRIM22 inhibited budding of virus-like particles containing Gag only, indicating that Gag was the target of TRIM22. TRIM22 did not block the release of MLV or EIAV Gag particles. Inhibition was associated with diffuse cytoplasmic staining of HIV Gag rather than accumulation at the plasma membrane, suggesting TRIM22 disrupts proper trafficking. Mutational analyses of TRIM22 showed that the catalytic amino acids Cys15 and Cys18 of the RING domain are required for TRIM22 antiviral activity. These data disclose a pathway by which Type 1 interferons obstruct HIV replication. Interferons are produced by cells in response to challenge by foreign pathogens such as viruses. The molecular mechanisms by which Type I interferons (e.g., IFNβ) inhibit the replication of HIV-1 are not fully clarified. We identified a gene called TRIM22 that belongs to the tripartite motif (TRIM) family that was strongly induced by IFNβ. Using RNA interference to reduce the expression of TRIM22, we showed that TRIM22 is a key mediator of the IFNβ response when expressed at natural levels. We demonstrate that TRIM22 blocks the intracellular trafficking of the viral structural protein Gag to the surface of the cell, and that the antiviral activity of TRIM22 is dependent on two cysteine residues (Cys15 and Cys18) that are critical for the E3 ligase activity of RING-containing proteins. This report describes a mechanism by which Type I interferons block HIV-1 replication.
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影响因子：
3.7
作者：
Bouazzaoui, Abdellatif;Kreutz, Marina;von Briesen, Hagen
通讯作者：
von Briesen, Hagen
影响因子：
5.4
作者：
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通讯作者：
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影响因子：
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作者：
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DOI：
10.1016/j.bbrc.2005.10.173
发表时间：
2005-12-30
影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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