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Cellular TRIM33 restrains HIV-1 infection by targeting viral integrase for proteasomal degradation

Research output: Contribution to journalArticle

Hashim Ali, Miguel Mano, Luca Braga, Asma Naseem, Bruna Marini, Diem My Vu, Chiara Collesi, Germana Meroni, Marina Lusic, Mauro Giacca

Original languageEnglish
Article number926
JournalNature Communications
Issue number1
Early online date25 Feb 2019
Publication statusPublished - 25 Feb 2019


King's Authors


Productive HIV-1 replication requires viral integrase (IN), which catalyzes integration of the viral genome into the host cell DNA. IN, however, is short lived and is rapidly degraded by the host ubiquitin-proteasome system. To identify the cellular factors responsible for HIV-1 IN degradation, we performed a targeted RNAi screen using a library of siRNAs against all components of the ubiquitin-conjugation machinery using high-content microscopy. Here we report that the E3 RING ligase TRIM33 is a major determinant of HIV-1 IN stability. CD4-positive cells with TRIM33 knock down show increased HIV-1 replication and proviral DNA formation, while those overexpressing the factor display opposite effects. Knock down of TRIM33 reverts the phenotype of an HIV-1 molecular clone carrying substitution of IN serine 57 to alanine, a mutation known to impair viral DNA integration. Thus, TRIM33 acts as a cellular factor restricting HIV-1 infection by preventing provirus formation.

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