1. The TRIM family protein KAP1 inhibits HIV-1 integration
- Author
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Awatef Allouch, Cristina Di Primio, Anna Cereseto, Emanuele Alpi, Marina Lusic, Daniele Arosio, Mauro Giacca, A., Allouch, C. D., Primio, E., Alpi, M., Lusic, D., Arosio, Giacca, Mauro, and A., Cereseto
- Subjects
Cancer Research ,genetics/metabolism, Virus Integration ,Virus Integration ,genetics/metabolism ,HIV Infections ,Histone Deacetylase 1 ,HIV Integrase ,Tripartite Motif-Containing Protein 28 ,Microbiology ,Cell Line ,genetics/metabolism, HIV-1 ,03 medical and health sciences ,0302 clinical medicine ,genetics/metabolism/virology ,Immunology and Microbiology(all) ,Virology ,Complementary DNA ,Humans ,Transferase ,Molecular Biology ,030304 developmental biology ,chemistry.chemical_classification ,0303 health sciences ,Acetylation, Cell Line, HIV Infections ,genetics/metabolism/virology, HIV Integrase ,enzymology/genetics/physiology, Histone Deacetylase 1 ,genetics/metabolism, Humans, Protein Binding, Repressor Proteins ,biology ,enzymology/genetics/physiology ,Acetylation ,Molecular biology ,HDAC1 ,3. Good health ,Cell biology ,Integrase ,Repressor Proteins ,Enzyme ,Histone ,chemistry ,030220 oncology & carcinogenesis ,Acetylation, Cell Line, HIV Infection ,HIV-1 ,biology.protein ,Parasitology ,TRIM Family ,Protein Binding ,genetics/metabolism, Humans, Protein Binding, Repressor Protein - Abstract
Summary 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.
- Published
- 2011
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