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

• Autor(a) principal: Ali, Hashim
• Data de Publicação: 2019
• Outros Autores: Mano, Miguel, Braga, Luca, Naseem, Asma, Marini, Bruna, Vu, Diem My, Collesi, Chiara, Meroni, Germana, Lusic, Marina, Giacca, Mauro
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10316/107185; https://doi.org/10.1038/s41467-019-08810-0
• topic: HIV Infections; HIV Integrase; HIV-1; Host-Pathogen Interactions; Humans; Proteasome Endopeptidase Complex; Protein Stability; Proteolysis; Proviruses; Transcription Factors; Virus Integration

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.