Productive HIV-1 replication requires viral integrase (IN), which catalyzes integration of theviral genome into the host cell DNA. IN, however, is short lived and is rapidly degraded bythe host ubiquitin-proteasome system. To identify the cellular factors responsible for HIV-1IN degradation, we performed a targeted RNAi screen using a library of siRNAs against allcomponents of the ubiquitin-conjugation machinery using high-content microscopy. Herewe 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 DNAformation, while those overexpressing the factor display opposite effects. Knock down ofTRIM33 reverts the phenotype of an HIV-1 molecular clone carrying substitution of INserine 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

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

Luca Braga;Bruna Marini;Chiara Collesi;Germana Meroni;Mauro Giacca
2019

Abstract

Productive HIV-1 replication requires viral integrase (IN), which catalyzes integration of theviral genome into the host cell DNA. IN, however, is short lived and is rapidly degraded bythe host ubiquitin-proteasome system. To identify the cellular factors responsible for HIV-1IN degradation, we performed a targeted RNAi screen using a library of siRNAs against allcomponents of the ubiquitin-conjugation machinery using high-content microscopy. Herewe 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 DNAformation, while those overexpressing the factor display opposite effects. Knock down ofTRIM33 reverts the phenotype of an HIV-1 molecular clone carrying substitution of INserine 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
Pubblicato
https://www.nature.com/articles/s41467-019-08810-0
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6389893/
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11368/2940185
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