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

Published version
Peer-reviewed

Type

Article

Change log

Authors

Ali, Hashim 
Braga, Luca 
Naseem, Asma 
Marini, Bruna 

Abstract

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.

Description

Keywords

HIV Infections, HIV Integrase, HIV-1, Host-Pathogen Interactions, Humans, Proteasome Endopeptidase Complex, Protein Stability, Proteolysis, Proviruses, Transcription Factors, Virus Integration

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

10

Publisher

Springer Science and Business Media LLC