Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C.

<h4>Background</h4>HIV-1 subtype B is the most prevalent in developed countries and, consequently, it has been extensively studied. On the other hand, subtype C is the most prevalent worldwide and therefore is a reasonable target for future studies. Here we evaluate the acquisition of re...

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Autores principales:	Rodrigo D Cunha, Celina M Abreu, Luis M F Gonzalez, Monique Nijhuis, Dorien de Jong, Renato S Aguiar, Adriana O Afonso, Rodrigo M Brindeiro, Amilcar Tanuri
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/22fe9d43fb964f1ca7cd43f2643f73e0
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spelling	oai:doaj.org-article:22fe9d43fb964f1ca7cd43f2643f73e02021-11-18T08:13:19ZDifferential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C.1932-620310.1371/journal.pone.0046622https://doaj.org/article/22fe9d43fb964f1ca7cd43f2643f73e02012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23056372/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>HIV-1 subtype B is the most prevalent in developed countries and, consequently, it has been extensively studied. On the other hand, subtype C is the most prevalent worldwide and therefore is a reasonable target for future studies. Here we evaluate the acquisition of resistance and the viability of HIV-1 subtype B and C RT clones from different isolates that were subjected to in vitro selection pressure with zidovudine (ZDV) and lamivudine (3TC).<h4>Methods/principal findings</h4>MT4 cells were infected with chimeric virus pseudotyped with RT from subtype B and C clones, which were previously subjected to serial passage with increasing concentrations of ZDV and 3TC. The samples collected after each passage were analyzed for the presence of resistance mutations and VL. No differences were found between subtypes B and C in viral load and resistance mutations when these viruses were selected with 3TC. However, the route of mutations and the time to rebound of subtype B and C virus were different when subjected to ZDV treatment. In order to confirm the role of the mutations detected, other clones were generated and subjected to in vitro selection. RT subtype B virus isolates tended to acquire different ZDV resistance mutations (Q151M and D67N or T215Y, D67D/N and F214L) compared to subtype C (D67N, K70R, T215I or T215F).<h4>Conclusions/significance</h4>This study suggests that different subtypes have a tendency to react differently to antiretroviral drug selection in vitro. Consequently, the acquisition of resistance in patients undergoing antiretroviral therapy can be dependent on the subtypes composing the viral population.Rodrigo D CunhaCelina M AbreuLuis M F GonzalezMonique NijhuisDorien de JongRenato S AguiarAdriana O AfonsoRodrigo M BrindeiroAmilcar TanuriPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 10, p e46622 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rodrigo D Cunha Celina M Abreu Luis M F Gonzalez Monique Nijhuis Dorien de Jong Renato S Aguiar Adriana O Afonso Rodrigo M Brindeiro Amilcar Tanuri Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C.
description	<h4>Background</h4>HIV-1 subtype B is the most prevalent in developed countries and, consequently, it has been extensively studied. On the other hand, subtype C is the most prevalent worldwide and therefore is a reasonable target for future studies. Here we evaluate the acquisition of resistance and the viability of HIV-1 subtype B and C RT clones from different isolates that were subjected to in vitro selection pressure with zidovudine (ZDV) and lamivudine (3TC).<h4>Methods/principal findings</h4>MT4 cells were infected with chimeric virus pseudotyped with RT from subtype B and C clones, which were previously subjected to serial passage with increasing concentrations of ZDV and 3TC. The samples collected after each passage were analyzed for the presence of resistance mutations and VL. No differences were found between subtypes B and C in viral load and resistance mutations when these viruses were selected with 3TC. However, the route of mutations and the time to rebound of subtype B and C virus were different when subjected to ZDV treatment. In order to confirm the role of the mutations detected, other clones were generated and subjected to in vitro selection. RT subtype B virus isolates tended to acquire different ZDV resistance mutations (Q151M and D67N or T215Y, D67D/N and F214L) compared to subtype C (D67N, K70R, T215I or T215F).<h4>Conclusions/significance</h4>This study suggests that different subtypes have a tendency to react differently to antiretroviral drug selection in vitro. Consequently, the acquisition of resistance in patients undergoing antiretroviral therapy can be dependent on the subtypes composing the viral population.
format	article
author	Rodrigo D Cunha Celina M Abreu Luis M F Gonzalez Monique Nijhuis Dorien de Jong Renato S Aguiar Adriana O Afonso Rodrigo M Brindeiro Amilcar Tanuri
author_facet	Rodrigo D Cunha Celina M Abreu Luis M F Gonzalez Monique Nijhuis Dorien de Jong Renato S Aguiar Adriana O Afonso Rodrigo M Brindeiro Amilcar Tanuri
author_sort	Rodrigo D Cunha
title	Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C.
title_short	Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C.
title_full	Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C.
title_fullStr	Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C.
title_full_unstemmed	Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C.
title_sort	differential in vitro kinetics of drug resistance mutation acquisition in hiv-1 rt of subtypes b and c.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/22fe9d43fb964f1ca7cd43f2643f73e0
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Differential in vitro kinetics of drug resistance mutation acquisition in HIV-1 RT of subtypes B and C.

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