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HIV-1 Tat protein induces DNA damage in human peripheral blood B-lymphocytes via mitochondrial ROS production
Human immunodeficiency virus (HIV) infection is associated with B-cell malignancies in patients though HIV-1 is not able to infect B-cells. The rate of B-cell lymphomas in HIV-infected individuals remains high even under the combined antiretroviral therapy (cART) that reconstitutes the immune functi...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5725280/ https://www.ncbi.nlm.nih.gov/pubmed/29220699 http://dx.doi.org/10.1016/j.redox.2017.11.024 |
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author | El-Amine, Rawan Germini, Diego Zakharova, Vlada V. Tsfasman, Tatyana Sheval, Eugene V. Louzada, Ruy A.N. Dupuy, Corinne Bilhou-Nabera, Chrystèle Hamade, Aline Najjar, Fadia Oksenhendler, Eric Lipinski, Marс Chernyak, Boris V. Vassetzky, Yegor S. |
author_facet | El-Amine, Rawan Germini, Diego Zakharova, Vlada V. Tsfasman, Tatyana Sheval, Eugene V. Louzada, Ruy A.N. Dupuy, Corinne Bilhou-Nabera, Chrystèle Hamade, Aline Najjar, Fadia Oksenhendler, Eric Lipinski, Marс Chernyak, Boris V. Vassetzky, Yegor S. |
author_sort | El-Amine, Rawan |
collection | PubMed |
description | Human immunodeficiency virus (HIV) infection is associated with B-cell malignancies in patients though HIV-1 is not able to infect B-cells. The rate of B-cell lymphomas in HIV-infected individuals remains high even under the combined antiretroviral therapy (cART) that reconstitutes the immune function. Thus, the contribution of HIV-1 to B-cell oncogenesis remains enigmatic. HIV-1 induces oxidative stress and DNA damage in infected cells via multiple mechanisms, including viral Tat protein. We have detected elevated levels of reactive oxygen species (ROS) and DNA damage in B-cells of HIV-infected individuals. As Tat is present in blood of infected individuals and is able to transduce cells, we hypothesized that it could induce oxidative DNA damage in B-cells promoting genetic instability and malignant transformation. Indeed, incubation of B-cells isolated from healthy donors with purified Tat protein led to oxidative stress, a decrease in the glutathione (GSH) levels, DNA damage and appearance of chromosomal aberrations. The effects of Tat relied on its transcriptional activity and were mediated by NF-κB activation. Tat stimulated oxidative stress in B-cells mostly via mitochondrial ROS production which depended on the reverse electron flow in Complex I of respiratory chain. We propose that Tat-induced oxidative stress, DNA damage and chromosomal aberrations are novel oncogenic factors favoring B-cell lymphomas in HIV-1 infected individuals. |
format | Online Article Text |
id | pubmed-5725280 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-57252802017-12-18 HIV-1 Tat protein induces DNA damage in human peripheral blood B-lymphocytes via mitochondrial ROS production El-Amine, Rawan Germini, Diego Zakharova, Vlada V. Tsfasman, Tatyana Sheval, Eugene V. Louzada, Ruy A.N. Dupuy, Corinne Bilhou-Nabera, Chrystèle Hamade, Aline Najjar, Fadia Oksenhendler, Eric Lipinski, Marс Chernyak, Boris V. Vassetzky, Yegor S. Redox Biol Research Paper Human immunodeficiency virus (HIV) infection is associated with B-cell malignancies in patients though HIV-1 is not able to infect B-cells. The rate of B-cell lymphomas in HIV-infected individuals remains high even under the combined antiretroviral therapy (cART) that reconstitutes the immune function. Thus, the contribution of HIV-1 to B-cell oncogenesis remains enigmatic. HIV-1 induces oxidative stress and DNA damage in infected cells via multiple mechanisms, including viral Tat protein. We have detected elevated levels of reactive oxygen species (ROS) and DNA damage in B-cells of HIV-infected individuals. As Tat is present in blood of infected individuals and is able to transduce cells, we hypothesized that it could induce oxidative DNA damage in B-cells promoting genetic instability and malignant transformation. Indeed, incubation of B-cells isolated from healthy donors with purified Tat protein led to oxidative stress, a decrease in the glutathione (GSH) levels, DNA damage and appearance of chromosomal aberrations. The effects of Tat relied on its transcriptional activity and were mediated by NF-κB activation. Tat stimulated oxidative stress in B-cells mostly via mitochondrial ROS production which depended on the reverse electron flow in Complex I of respiratory chain. We propose that Tat-induced oxidative stress, DNA damage and chromosomal aberrations are novel oncogenic factors favoring B-cell lymphomas in HIV-1 infected individuals. Elsevier 2017-12-07 /pmc/articles/PMC5725280/ /pubmed/29220699 http://dx.doi.org/10.1016/j.redox.2017.11.024 Text en © 2017 Published by Elsevier B.V. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research Paper El-Amine, Rawan Germini, Diego Zakharova, Vlada V. Tsfasman, Tatyana Sheval, Eugene V. Louzada, Ruy A.N. Dupuy, Corinne Bilhou-Nabera, Chrystèle Hamade, Aline Najjar, Fadia Oksenhendler, Eric Lipinski, Marс Chernyak, Boris V. Vassetzky, Yegor S. HIV-1 Tat protein induces DNA damage in human peripheral blood B-lymphocytes via mitochondrial ROS production |
title | HIV-1 Tat protein induces DNA damage in human peripheral blood B-lymphocytes via mitochondrial ROS production |
title_full | HIV-1 Tat protein induces DNA damage in human peripheral blood B-lymphocytes via mitochondrial ROS production |
title_fullStr | HIV-1 Tat protein induces DNA damage in human peripheral blood B-lymphocytes via mitochondrial ROS production |
title_full_unstemmed | HIV-1 Tat protein induces DNA damage in human peripheral blood B-lymphocytes via mitochondrial ROS production |
title_short | HIV-1 Tat protein induces DNA damage in human peripheral blood B-lymphocytes via mitochondrial ROS production |
title_sort | hiv-1 tat protein induces dna damage in human peripheral blood b-lymphocytes via mitochondrial ros production |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5725280/ https://www.ncbi.nlm.nih.gov/pubmed/29220699 http://dx.doi.org/10.1016/j.redox.2017.11.024 |
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