title: The TRIM family protein KAP1 inhibits HIV-1 integration.
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.
authors.affiliation: Molecular Biology Laboratory, Scuola Normale Superiore, Piazza dei Cavalieri 7, Pisa 56126, Italy.
authors.forename: Awatef
authors.initials: A
authors.lastname: Allouch
authors.forename: Cristina
authors.initials: C
authors.lastname: Di Primio
authors.forename: Emanuele
authors.initials: E
authors.lastname: Alpi
authors.forename: Marina
authors.initials: M
authors.lastname: Lusic
authors.forename: Daniele
authors.initials: D
authors.lastname: Arosio
authors.forename: Mauro
authors.initials: M
authors.lastname: Giacca
authors.forename: Anna
authors.initials: A
authors.lastname: Cereseto
mesh_terms: D000107:Acetylation; D002460:Cell Line; D015658:HIV Infections / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D019427:HIV Integrase / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000201:enzymology / Q000235:genetics / Q000502:physiology*; D056284:Histone Deacetylase 1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D011485:Protein Binding; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D000076183:Tripartite Motif-Containing Protein 28; D016662:Virus Integration
chemical_list: D012097:Repressor Proteins; C101116:TRIM28 protein, human; D000076183:Tripartite Motif-Containing Protein 28; D019427:HIV Integrase; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1