Cargando…
Cyclophilin A protects HIV-1 from restriction by human TRIM5α
The HIV-1 capsid (CA) protein lattice encases viral genomic RNA and regulates steps essential to target cell invasion(1). Cyclophilin A (CypA) has interacted with the CA of lentiviruses related to HIV-1 for millions of years(2–7). Disruption of the CA-CypA interaction decreases HIV-1 infectivity in...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6879858/ https://www.ncbi.nlm.nih.gov/pubmed/31636416 http://dx.doi.org/10.1038/s41564-019-0592-5 |
_version_ | 1783473671674789888 |
---|---|
author | Kim, Kyusik Dauphin, Ann Komurlu, Sevnur McCauley, Sean M. Yurkovetskiy, Leonid A. Carbone, Claudia Diehl, William E. Strambio-De-Castillia, Caterina Campbell, Edward M. Luban, Jeremy |
author_facet | Kim, Kyusik Dauphin, Ann Komurlu, Sevnur McCauley, Sean M. Yurkovetskiy, Leonid A. Carbone, Claudia Diehl, William E. Strambio-De-Castillia, Caterina Campbell, Edward M. Luban, Jeremy |
author_sort | Kim, Kyusik |
collection | PubMed |
description | The HIV-1 capsid (CA) protein lattice encases viral genomic RNA and regulates steps essential to target cell invasion(1). Cyclophilin A (CypA) has interacted with the CA of lentiviruses related to HIV-1 for millions of years(2–7). Disruption of the CA-CypA interaction decreases HIV-1 infectivity in human cells(8–12), but stimulates infectivity in non-human primate cells(13–15). Genetic and biochemical data suggest that CypA protects HIV-1 from a CA-specific restriction factor in human cells(16–20). Discovery of the CA-specific restriction factor tripartite-containing motif 5α (TRIM5α)(21), and of multiple, independently-derived, TRIM5-CypA fusion genes(4,5,15,22–26), pointed to human TRIM5α as the CypA-sensitive restriction factor. However, HIV-1 restriction by human TRIM5α in tumor cell lines is minimal(21), and inhibition of such activity by CypA has not been detected(27). Here, exploiting reverse genetic tools optimized for primary human blood cells, we demonstrate that disruption of the CA-CypA interaction renders HIV-1 susceptible to potent restriction by human TRIM5α, with the block occurring before reverse transcription. Endogenous TRIM5α associated with virion cores as they entered the cytoplasm, but only when the CA-CypA interaction was disrupted. These experiments resolve the long-standing mystery of the role of CypA in HIV-1 replication by demonstrating that this ubiquitous cellular protein shields HIV-1 from previously inapparent restriction by human TRIM5α. |
format | Online Article Text |
id | pubmed-6879858 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
record_format | MEDLINE/PubMed |
spelling | pubmed-68798582020-04-21 Cyclophilin A protects HIV-1 from restriction by human TRIM5α Kim, Kyusik Dauphin, Ann Komurlu, Sevnur McCauley, Sean M. Yurkovetskiy, Leonid A. Carbone, Claudia Diehl, William E. Strambio-De-Castillia, Caterina Campbell, Edward M. Luban, Jeremy Nat Microbiol Article The HIV-1 capsid (CA) protein lattice encases viral genomic RNA and regulates steps essential to target cell invasion(1). Cyclophilin A (CypA) has interacted with the CA of lentiviruses related to HIV-1 for millions of years(2–7). Disruption of the CA-CypA interaction decreases HIV-1 infectivity in human cells(8–12), but stimulates infectivity in non-human primate cells(13–15). Genetic and biochemical data suggest that CypA protects HIV-1 from a CA-specific restriction factor in human cells(16–20). Discovery of the CA-specific restriction factor tripartite-containing motif 5α (TRIM5α)(21), and of multiple, independently-derived, TRIM5-CypA fusion genes(4,5,15,22–26), pointed to human TRIM5α as the CypA-sensitive restriction factor. However, HIV-1 restriction by human TRIM5α in tumor cell lines is minimal(21), and inhibition of such activity by CypA has not been detected(27). Here, exploiting reverse genetic tools optimized for primary human blood cells, we demonstrate that disruption of the CA-CypA interaction renders HIV-1 susceptible to potent restriction by human TRIM5α, with the block occurring before reverse transcription. Endogenous TRIM5α associated with virion cores as they entered the cytoplasm, but only when the CA-CypA interaction was disrupted. These experiments resolve the long-standing mystery of the role of CypA in HIV-1 replication by demonstrating that this ubiquitous cellular protein shields HIV-1 from previously inapparent restriction by human TRIM5α. 2019-10-21 2019-12 /pmc/articles/PMC6879858/ /pubmed/31636416 http://dx.doi.org/10.1038/s41564-019-0592-5 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Kim, Kyusik Dauphin, Ann Komurlu, Sevnur McCauley, Sean M. Yurkovetskiy, Leonid A. Carbone, Claudia Diehl, William E. Strambio-De-Castillia, Caterina Campbell, Edward M. Luban, Jeremy Cyclophilin A protects HIV-1 from restriction by human TRIM5α |
title | Cyclophilin A protects HIV-1 from restriction by human TRIM5α |
title_full | Cyclophilin A protects HIV-1 from restriction by human TRIM5α |
title_fullStr | Cyclophilin A protects HIV-1 from restriction by human TRIM5α |
title_full_unstemmed | Cyclophilin A protects HIV-1 from restriction by human TRIM5α |
title_short | Cyclophilin A protects HIV-1 from restriction by human TRIM5α |
title_sort | cyclophilin a protects hiv-1 from restriction by human trim5α |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6879858/ https://www.ncbi.nlm.nih.gov/pubmed/31636416 http://dx.doi.org/10.1038/s41564-019-0592-5 |
work_keys_str_mv | AT kimkyusik cyclophilinaprotectshiv1fromrestrictionbyhumantrim5a AT dauphinann cyclophilinaprotectshiv1fromrestrictionbyhumantrim5a AT komurlusevnur cyclophilinaprotectshiv1fromrestrictionbyhumantrim5a AT mccauleyseanm cyclophilinaprotectshiv1fromrestrictionbyhumantrim5a AT yurkovetskiyleonida cyclophilinaprotectshiv1fromrestrictionbyhumantrim5a AT carboneclaudia cyclophilinaprotectshiv1fromrestrictionbyhumantrim5a AT diehlwilliame cyclophilinaprotectshiv1fromrestrictionbyhumantrim5a AT strambiodecastilliacaterina cyclophilinaprotectshiv1fromrestrictionbyhumantrim5a AT campbelledwardm cyclophilinaprotectshiv1fromrestrictionbyhumantrim5a AT lubanjeremy cyclophilinaprotectshiv1fromrestrictionbyhumantrim5a |