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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2014
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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. |
format | Online Article Text |
id | pubmed-4189035 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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