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Fitness Impaired Drug Resistant HIV-1 Is Not Compromised in Cell-to-Cell Transmission or Establishment of and Reactivation from Latency

Both the presence of latently infected cells and cell-to-cell viral transmission are means whereby HIV can partially evade the inhibitory activities of antiretroviral drugs. The clinical use of a novel integrase inhibitor, dolutegravir (DTG), has established hope that this compound may limit HIV per...

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Autores principales: Bastarache, Sophie M., Mesplède, Thibault, Donahue, Daniel A., Sloan, Richard D., Wainberg, Mark A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4189035/
https://www.ncbi.nlm.nih.gov/pubmed/25243372
http://dx.doi.org/10.3390/v6093487
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author Bastarache, Sophie M.
Mesplède, Thibault
Donahue, Daniel A.
Sloan, Richard D.
Wainberg, Mark A.
author_facet Bastarache, Sophie M.
Mesplède, Thibault
Donahue, Daniel A.
Sloan, Richard D.
Wainberg, Mark A.
author_sort Bastarache, Sophie M.
collection PubMed
description Both the presence of latently infected cells and cell-to-cell viral transmission are means whereby HIV can partially evade the inhibitory activities of antiretroviral drugs. The clinical use of a novel integrase inhibitor, dolutegravir (DTG), has established hope that this compound may limit HIV persistence, since no treatment-naïve patient treated with DTG has yet developed resistance against this drug, even though a R263K substitution in integrase confers low-level resistance to this drug in tissue culture. Here, we have studied the impact of R263K on HIV replication capacity and the ability of HIV to establish or be reactivated from latency and/or spread through cell-to-cell transmission. We affirm that DTG-resistant viruses have diminished capacity to replicate and establish infection. However, DTG-resistant viruses were efficiently transmitted via cell-to-cell contacts, and were as likely to establish and be reactivated from latent infection as wildtype viruses. Both cell-to-cell transmission of HIV and the establishment of and reemergence from latency are important for the establishment and maintenance of viral reservoirs. Since the DTG and other drug-resistant viruses studied here do not seem to have been impaired in regard to these activities, studies should be undertaken to characterize HIV reservoirs in patients who have been treated with DTG.
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spelling pubmed-41890352014-10-08 Fitness Impaired Drug Resistant HIV-1 Is Not Compromised in Cell-to-Cell Transmission or Establishment of and Reactivation from Latency Bastarache, Sophie M. Mesplède, Thibault Donahue, Daniel A. Sloan, Richard D. Wainberg, Mark A. Viruses Article Both the presence of latently infected cells and cell-to-cell viral transmission are means whereby HIV can partially evade the inhibitory activities of antiretroviral drugs. The clinical use of a novel integrase inhibitor, dolutegravir (DTG), has established hope that this compound may limit HIV persistence, since no treatment-naïve patient treated with DTG has yet developed resistance against this drug, even though a R263K substitution in integrase confers low-level resistance to this drug in tissue culture. Here, we have studied the impact of R263K on HIV replication capacity and the ability of HIV to establish or be reactivated from latency and/or spread through cell-to-cell transmission. We affirm that DTG-resistant viruses have diminished capacity to replicate and establish infection. However, DTG-resistant viruses were efficiently transmitted via cell-to-cell contacts, and were as likely to establish and be reactivated from latent infection as wildtype viruses. Both cell-to-cell transmission of HIV and the establishment of and reemergence from latency are important for the establishment and maintenance of viral reservoirs. Since the DTG and other drug-resistant viruses studied here do not seem to have been impaired in regard to these activities, studies should be undertaken to characterize HIV reservoirs in patients who have been treated with DTG. MDPI 2014-09-19 /pmc/articles/PMC4189035/ /pubmed/25243372 http://dx.doi.org/10.3390/v6093487 Text en © 2014 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Bastarache, Sophie M.
Mesplède, Thibault
Donahue, Daniel A.
Sloan, Richard D.
Wainberg, Mark A.
Fitness Impaired Drug Resistant HIV-1 Is Not Compromised in Cell-to-Cell Transmission or Establishment of and Reactivation from Latency
title Fitness Impaired Drug Resistant HIV-1 Is Not Compromised in Cell-to-Cell Transmission or Establishment of and Reactivation from Latency
title_full Fitness Impaired Drug Resistant HIV-1 Is Not Compromised in Cell-to-Cell Transmission or Establishment of and Reactivation from Latency
title_fullStr Fitness Impaired Drug Resistant HIV-1 Is Not Compromised in Cell-to-Cell Transmission or Establishment of and Reactivation from Latency
title_full_unstemmed Fitness Impaired Drug Resistant HIV-1 Is Not Compromised in Cell-to-Cell Transmission or Establishment of and Reactivation from Latency
title_short Fitness Impaired Drug Resistant HIV-1 Is Not Compromised in Cell-to-Cell Transmission or Establishment of and Reactivation from Latency
title_sort fitness impaired drug resistant hiv-1 is not compromised in cell-to-cell transmission or establishment of and reactivation from latency
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4189035/
https://www.ncbi.nlm.nih.gov/pubmed/25243372
http://dx.doi.org/10.3390/v6093487
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