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

Research output: Contribution to journalArticlepeer-review

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
Pages (from-to)1-15
Number of pages15
JournalNature Communications
Issue number1
Early online date25 Feb 2019
Accepted/In press23 Jan 2019
E-pub ahead of print25 Feb 2019
Published25 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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