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

Nature Communications
Hashim AliMauro Giacca

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.

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Citations

May 24, 2019·Biological Chemistry·Felix Preston WilliamsJanosch Hennig
Oct 30, 2019·The Journal of General Virology·Adam Hage, Ricardo Rajsbaum
Jun 30, 2019·International Journal of Molecular Sciences·Vivian K Rojas, In-Woo Park
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Jan 6, 2021·International Journal of Molecular Sciences·Ramesh KumarSujatha Sunil
Jan 23, 2021·Chembiochem : a European Journal of Chemical Biology·Francesca D'AmicoMonique P C Mulder
Apr 2, 2021·Frontiers in Cellular and Infection Microbiology·Zhou ShenMiao Li
Mar 24, 2021·Cold Spring Harbor Perspectives in Biology·Bojana LucicMarina Lusic
Aug 8, 2021·Microorganisms·Ilena BenoitRenée N Douville
Aug 28, 2021·Cells·Isabel PaganiElisa Vicenzi
Sep 15, 2021·Journal of Cellular Biochemistry·Ankur R DubeyAmit Mishra

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Methods Mentioned

BETA
ubiquitination
transfection
protein knock-down
co-immunoprecipitation
pull-down
immunoprecipitation
polyubiquitination
ELISA
deamination
two hybrid

Software Mentioned

MetaXpress
ImageXpress

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