Cellular TRIM33 restrains HIV-1 infection by targeting viral integrase for proteasomal degradation
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , , , , , , , , |
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 |
Resumo: | 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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Cellular TRIM33 restrains HIV-1 infection by targeting viral integrase for proteasomal degradationHIV InfectionsHIV IntegraseHIV-1Host-Pathogen InteractionsHumansProteasome Endopeptidase ComplexProtein StabilityProteolysisProvirusesTranscription FactorsVirus IntegrationProductive 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.Springer Nature2019-02-25info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/107185http://hdl.handle.net/10316/107185https://doi.org/10.1038/s41467-019-08810-0eng2041-1723Ali, HashimMano, MiguelBraga, LucaNaseem, AsmaMarini, BrunaVu, Diem MyCollesi, ChiaraMeroni, GermanaLusic, MarinaGiacca, Mauroinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-06-13T11:10:11Zoai:estudogeral.uc.pt:10316/107185Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:23:32.730483Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
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 |
spellingShingle |
Cellular TRIM33 restrains HIV-1 infection by targeting viral integrase for proteasomal degradation Ali, Hashim HIV Infections HIV Integrase HIV-1 Host-Pathogen Interactions Humans Proteasome Endopeptidase Complex Protein Stability Proteolysis Proviruses Transcription Factors Virus Integration |
title_short |
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_sort |
Cellular TRIM33 restrains HIV-1 infection by targeting viral integrase for proteasomal degradation |
author |
Ali, Hashim |
author_facet |
Ali, Hashim Mano, Miguel Braga, Luca Naseem, Asma Marini, Bruna Vu, Diem My Collesi, Chiara Meroni, Germana Lusic, Marina Giacca, Mauro |
author_role |
author |
author2 |
Mano, Miguel Braga, Luca Naseem, Asma Marini, Bruna Vu, Diem My Collesi, Chiara Meroni, Germana Lusic, Marina Giacca, Mauro |
author2_role |
author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Ali, Hashim Mano, Miguel Braga, Luca Naseem, Asma Marini, Bruna Vu, Diem My Collesi, Chiara Meroni, Germana Lusic, Marina Giacca, Mauro |
dc.subject.por.fl_str_mv |
HIV Infections HIV Integrase HIV-1 Host-Pathogen Interactions Humans Proteasome Endopeptidase Complex Protein Stability Proteolysis Proviruses Transcription Factors Virus Integration |
topic |
HIV Infections HIV Integrase HIV-1 Host-Pathogen Interactions Humans Proteasome Endopeptidase Complex Protein Stability Proteolysis Proviruses Transcription Factors Virus Integration |
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. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-02-25 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10316/107185 http://hdl.handle.net/10316/107185 https://doi.org/10.1038/s41467-019-08810-0 |
url |
http://hdl.handle.net/10316/107185 https://doi.org/10.1038/s41467-019-08810-0 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
2041-1723 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Springer Nature |
publisher.none.fl_str_mv |
Springer Nature |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799134122230153216 |