The TRIM Family Protein KAP1 Inhibits HIV-1 Integration
Copyright policy )The TRIM Family Protein KAP1 Inhibits HIV-1 Integration
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.
- National Research Council Italy
- European Molecular Biology Laboratory Italy
- National Research Council Sri Lanka
- Istituto di Biofisica Italy
- University of Trieste Italy
Cancer Research, Acetylation, Cell Line, HIV Infections; genetics/metabolism/virology, HIV Integrase; genetics/metabolism, HIV-1; enzymology/genetics/physiology, Histone Deacetylase 1; genetics/metabolism, Humans, Protein Binding, Repressor Proteins; genetics/metabolism, Virus Integration, genetics/metabolism, Virus Integration, Virus Integration, enzymology/genetics/physiology, Histone Deacetylase 1, Acetylation, HIV Infections, Histone Deacetylase 1, HIV Integrase, Tripartite Motif-Containing Protein 28, Cell Line, genetics/metabolism, HIV-1, Repressor Proteins, Immunology and Microbiology(all), Acetylation, Cell Line, HIV Infection, genetics/metabolism/virology, HIV Integrase, HIV-1, Humans, Molecular Biology, genetics/metabolism, Humans, Protein Binding, Repressor Protein, Protein Binding
Cancer Research, Acetylation, Cell Line, HIV Infections; genetics/metabolism/virology, HIV Integrase; genetics/metabolism, HIV-1; enzymology/genetics/physiology, Histone Deacetylase 1; genetics/metabolism, Humans, Protein Binding, Repressor Proteins; genetics/metabolism, Virus Integration, genetics/metabolism, Virus Integration, Virus Integration, enzymology/genetics/physiology, Histone Deacetylase 1, Acetylation, HIV Infections, Histone Deacetylase 1, HIV Integrase, Tripartite Motif-Containing Protein 28, Cell Line, genetics/metabolism, HIV-1, Repressor Proteins, Immunology and Microbiology(all), Acetylation, Cell Line, HIV Infection, genetics/metabolism/virology, HIV Integrase, HIV-1, Humans, Molecular Biology, genetics/metabolism, Humans, Protein Binding, Repressor Protein, Protein Binding
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