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Tetraspanins regulate cell-to-cell transmission of HIV-1

BACKGROUND: The presence of the tetraspanins CD9, CD63, CD81 and CD82 at HIV-1 budding sites, at the virological synapse (VS), and their enrichment in HIV-1 virions has been well-documented, but it remained unclear if these proteins play a role in the late phase of the viral replication cycle. Here...

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Autores principales: Krementsov, Dimitry N, Weng, Jia, Lambelé, Marie, Roy, Nathan H, Thali, Markus
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2714829/
https://www.ncbi.nlm.nih.gov/pubmed/19602278
http://dx.doi.org/10.1186/1742-4690-6-64
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author Krementsov, Dimitry N
Weng, Jia
Lambelé, Marie
Roy, Nathan H
Thali, Markus
author_facet Krementsov, Dimitry N
Weng, Jia
Lambelé, Marie
Roy, Nathan H
Thali, Markus
author_sort Krementsov, Dimitry N
collection PubMed
description BACKGROUND: The presence of the tetraspanins CD9, CD63, CD81 and CD82 at HIV-1 budding sites, at the virological synapse (VS), and their enrichment in HIV-1 virions has been well-documented, but it remained unclear if these proteins play a role in the late phase of the viral replication cycle. Here we used overexpression and knockdown approaches to address this question. RESULTS: Neither ablation of CD9, CD63 and/or CD81, nor overexpression of these tetraspanins was found to affect the efficiency of virus release. However, confirming recently reported data, tetraspanin overexpression in virus-producing cells resulted in the release of virions with substantially reduced infectivity. We also investigated the roles of these tetraspanins in cell-to-cell transmission of HIV-1. Overexpression of CD9 and CD63 led to reduced cell-to-cell transmission of this virus. Interestingly, in knockdown experiments we found that ablation of CD63, CD9 and/or CD81 had no effect on cell-free infectivity. However, knockdown of CD81, but not CD9 and CD63, enhanced productive particle transmission to target cells, suggesting additional roles for tetraspanins in the transmission process. Finally, tetraspanins were found to be downregulated in HIV-1-infected T lymphocytes, suggesting that HIV-1 modulates the levels of these proteins in order to maximize the efficiency of its transmission within the host. CONCLUSION: Altogether, these results establish an active role of tetraspanins in HIV-1 producer cells.
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spelling pubmed-27148292009-07-24 Tetraspanins regulate cell-to-cell transmission of HIV-1 Krementsov, Dimitry N Weng, Jia Lambelé, Marie Roy, Nathan H Thali, Markus Retrovirology Research BACKGROUND: The presence of the tetraspanins CD9, CD63, CD81 and CD82 at HIV-1 budding sites, at the virological synapse (VS), and their enrichment in HIV-1 virions has been well-documented, but it remained unclear if these proteins play a role in the late phase of the viral replication cycle. Here we used overexpression and knockdown approaches to address this question. RESULTS: Neither ablation of CD9, CD63 and/or CD81, nor overexpression of these tetraspanins was found to affect the efficiency of virus release. However, confirming recently reported data, tetraspanin overexpression in virus-producing cells resulted in the release of virions with substantially reduced infectivity. We also investigated the roles of these tetraspanins in cell-to-cell transmission of HIV-1. Overexpression of CD9 and CD63 led to reduced cell-to-cell transmission of this virus. Interestingly, in knockdown experiments we found that ablation of CD63, CD9 and/or CD81 had no effect on cell-free infectivity. However, knockdown of CD81, but not CD9 and CD63, enhanced productive particle transmission to target cells, suggesting additional roles for tetraspanins in the transmission process. Finally, tetraspanins were found to be downregulated in HIV-1-infected T lymphocytes, suggesting that HIV-1 modulates the levels of these proteins in order to maximize the efficiency of its transmission within the host. CONCLUSION: Altogether, these results establish an active role of tetraspanins in HIV-1 producer cells. BioMed Central 2009-07-14 /pmc/articles/PMC2714829/ /pubmed/19602278 http://dx.doi.org/10.1186/1742-4690-6-64 Text en Copyright © 2009 Krementsov et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Krementsov, Dimitry N
Weng, Jia
Lambelé, Marie
Roy, Nathan H
Thali, Markus
Tetraspanins regulate cell-to-cell transmission of HIV-1
title Tetraspanins regulate cell-to-cell transmission of HIV-1
title_full Tetraspanins regulate cell-to-cell transmission of HIV-1
title_fullStr Tetraspanins regulate cell-to-cell transmission of HIV-1
title_full_unstemmed Tetraspanins regulate cell-to-cell transmission of HIV-1
title_short Tetraspanins regulate cell-to-cell transmission of HIV-1
title_sort tetraspanins regulate cell-to-cell transmission of hiv-1
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2714829/
https://www.ncbi.nlm.nih.gov/pubmed/19602278
http://dx.doi.org/10.1186/1742-4690-6-64
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