TRIM 家族蛋白 KAP1 抑制 HIV-1 整合。

The TRIM family protein KAP1 inhibits HIV-1 integration.

机构信息

Molecular Biology Laboratory, Scuola Normale Superiore, Piazza dei Cavalieri 7, Pisa 56126, Italy.

出版信息

Cell Host Microbe. 2011 Jun 16;9(6):484-95. doi: 10.1016/j.chom.2011.05.004.

DOI:10.1016/j.chom.2011.05.004

Abstract

The integration of viral cDNA into the host genome is a critical step in the life cycle of HIV-1. This step is catalyzed by integrase (IN), a viral enzyme that is positively regulated by acetylation via the cellular histone acetyl transferase (HAT) p300. To investigate the relevance of IN acetylation, we searched for cellular proteins that selectively bind acetylated IN and identified KAP1, a protein belonging to the TRIM family of antiviral proteins. KAP1 binds acetylated IN and induces its deacetylation through the formation of a protein complex which includes the deacetylase HDAC1. Modulation of intracellular KAP1 levels in different cell types including T cells, the primary HIV-1 target, revealed that KAP1 curtails viral infectivity by selectively affecting HIV-1 integration. This study identifies KAP1 as a cellular factor restricting HIV-1 infection and underscores the relevance of IN acetylation as a crucial step in the viral infectious cycle.

摘要

病毒 cDNA 整合到宿主基因组是 HIV-1 生命周期中的一个关键步骤。这一步由整合酶（IN）催化，整合酶是一种通过细胞组蛋白乙酰转移酶（HAT）p300 的乙酰化作用正调控的病毒酶。为了研究 IN 乙酰化的相关性，我们搜索了选择性结合乙酰化 IN 的细胞蛋白，并鉴定出 KAP1，一种属于抗病毒蛋白 TRIM 家族的蛋白质。KAP1 结合乙酰化的 IN，并通过形成包括去乙酰化酶 HDAC1 在内的蛋白质复合物诱导其去乙酰化。在包括 T 细胞在内的不同细胞类型中调节细胞内 KAP1 水平，揭示了 KAP1 通过选择性影响 HIV-1 整合来限制病毒感染性。本研究将 KAP1 鉴定为一种限制 HIV-1 感染的细胞因子，并强调了 IN 乙酰化作为病毒感染周期中关键步骤的相关性。