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Cellular TRIM33 restrains HIV-1 infection by targeting viral integrase for proteasomal degradation
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 p...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6389893/ https://www.ncbi.nlm.nih.gov/pubmed/30804369 http://dx.doi.org/10.1038/s41467-019-08810-0 |
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author | Ali, Hashim Mano, Miguel Braga, Luca Naseem, Asma Marini, Bruna Vu, Diem My Collesi, Chiara Meroni, Germana Lusic, Marina Giacca, Mauro |
author_facet | Ali, Hashim Mano, Miguel Braga, Luca Naseem, Asma Marini, Bruna Vu, Diem My Collesi, Chiara Meroni, Germana Lusic, Marina Giacca, Mauro |
author_sort | Ali, Hashim |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6389893 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-63898932019-02-27 Cellular TRIM33 restrains HIV-1 infection by targeting viral integrase for proteasomal degradation Ali, Hashim Mano, Miguel Braga, Luca Naseem, Asma Marini, Bruna Vu, Diem My Collesi, Chiara Meroni, Germana Lusic, Marina Giacca, Mauro Nat Commun Article 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. Nature Publishing Group UK 2019-02-25 /pmc/articles/PMC6389893/ /pubmed/30804369 http://dx.doi.org/10.1038/s41467-019-08810-0 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Ali, Hashim Mano, Miguel Braga, Luca Naseem, Asma Marini, Bruna Vu, Diem My Collesi, Chiara Meroni, Germana Lusic, Marina Giacca, Mauro Cellular TRIM33 restrains HIV-1 infection by targeting viral integrase for proteasomal degradation |
title | Cellular TRIM33 restrains HIV-1 infection by targeting viral integrase for proteasomal degradation |
title_full | Cellular TRIM33 restrains HIV-1 infection by targeting viral integrase for proteasomal degradation |
title_fullStr | Cellular TRIM33 restrains HIV-1 infection by targeting viral integrase for proteasomal degradation |
title_full_unstemmed | Cellular TRIM33 restrains HIV-1 infection by targeting viral integrase for proteasomal degradation |
title_short | Cellular TRIM33 restrains HIV-1 infection by targeting viral integrase for proteasomal degradation |
title_sort | cellular trim33 restrains hiv-1 infection by targeting viral integrase for proteasomal degradation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6389893/ https://www.ncbi.nlm.nih.gov/pubmed/30804369 http://dx.doi.org/10.1038/s41467-019-08810-0 |
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