The TRIM Family Protein KAP1 Inhibits HIV-1 Integration

被引：102

作者：

Allouch, Awatef ^{[1
]}

Di Primio, Cristina ^{[1
]}

Alpi, Emanuele ^{[1
]}

Lusic, Marina ^{[2
]}

Arosio, Daniele ^{[3
,4
]}

Giacca, Mauro ^{[2
]}

Cereseto, Anna ^{[1
,5
]}

机构：

[1] Scuola Normale Super Pisa, Mol Biol Lab, I-56126 Pisa, Italy

[2] Int Ctr Genet Engn & Biotechnol, Mol Med Lab, I-34012 Trieste, Italy

[3] CNR, Ist Biofis, I-38100 Trento, Italy

[4] FBK, I-38100 Trento, Italy

[5] Univ Trent, Ctr Integrat Biol, Mol Virol Lab, I-38123 Trento, Italy

来源：

CELL HOST & MICROBE | 2011年 / 9卷 / 06期

关键词：

NUCLEAR COREPRESSOR KAP1; ZINC-FINGER PROTEINS; EMBRYONIC STEM-CELLS; TRANSCRIPTIONAL REPRESSION; RETROVIRAL INFECTION; VIRAL INTEGRATION; DNA INTEGRATION; DAMAGE RESPONSE; CULTURED-CELLS; VIRUS;

D O I：

10.1016/j.chom.2011.05.004

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

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.

引用

页码：484 / 495

页数：12

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