Unique C2V3 sequence in HIV-1 envelope obtained from broadly neutralizing plasma of a slow progressing patient conferred enhanced virus neutralization.

Broadly neutralizing antibodies to HIV-1 usually develops in chronic infections. Here, we examined the basis of enhanced sensitivity of an env clone amplified from cross neutralizing plasma of an antiretroviral naïve chronically infected Indian patient (ID50 >600-fold higher compared to other aut...

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Main Authors: Rajesh Ringe, Lipsa Das, Ipsita Choudhary, Deepak Sharma, Ramesh Paranjape, Virander Singh Chauhan, Jayanta Bhattacharya
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3463516?pdf=render
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author Rajesh Ringe
Lipsa Das
Ipsita Choudhary
Deepak Sharma
Ramesh Paranjape
Virander Singh Chauhan
Jayanta Bhattacharya
author_facet Rajesh Ringe
Lipsa Das
Ipsita Choudhary
Deepak Sharma
Ramesh Paranjape
Virander Singh Chauhan
Jayanta Bhattacharya
author_sort Rajesh Ringe
collection DOAJ
description Broadly neutralizing antibodies to HIV-1 usually develops in chronic infections. Here, we examined the basis of enhanced sensitivity of an env clone amplified from cross neutralizing plasma of an antiretroviral naïve chronically infected Indian patient (ID50 >600-fold higher compared to other autologous env clones). The enhanced autologous neutralization of pseudotyped viruses expressing the sensitive envelope (Env) was associated with increased sensitivity to reagents and monoclonal antibodies targeting distinct sites in Env. Chimeric viruses constructed by swapping fragments of sensitive Env into resistant Env backbone revealed that the presence of unique residues within C2V3 region of gp120 governed increased neutralization. The enhanced virus neutralization was also associated with low CD4 dependence as well as increased binding of Env trimers to IgG1b12 and CD4-IgG2 and was independent of gp120 shedding. Our data highlighted vulnerabilities in the Env obtained from cross neutralizing plasma associated with the exposure of discontinuous neutralizing epitopes and enhanced autologous neutralization. Such information may aid in Env-based vaccine immunogen design.
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spelling doaj.art-161ab5a0a66542f6a7aee5da352261482022-12-21T19:08:19ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01710e4671310.1371/journal.pone.0046713Unique C2V3 sequence in HIV-1 envelope obtained from broadly neutralizing plasma of a slow progressing patient conferred enhanced virus neutralization.Rajesh RingeLipsa DasIpsita ChoudharyDeepak SharmaRamesh ParanjapeVirander Singh ChauhanJayanta BhattacharyaBroadly neutralizing antibodies to HIV-1 usually develops in chronic infections. Here, we examined the basis of enhanced sensitivity of an env clone amplified from cross neutralizing plasma of an antiretroviral naïve chronically infected Indian patient (ID50 >600-fold higher compared to other autologous env clones). The enhanced autologous neutralization of pseudotyped viruses expressing the sensitive envelope (Env) was associated with increased sensitivity to reagents and monoclonal antibodies targeting distinct sites in Env. Chimeric viruses constructed by swapping fragments of sensitive Env into resistant Env backbone revealed that the presence of unique residues within C2V3 region of gp120 governed increased neutralization. The enhanced virus neutralization was also associated with low CD4 dependence as well as increased binding of Env trimers to IgG1b12 and CD4-IgG2 and was independent of gp120 shedding. Our data highlighted vulnerabilities in the Env obtained from cross neutralizing plasma associated with the exposure of discontinuous neutralizing epitopes and enhanced autologous neutralization. Such information may aid in Env-based vaccine immunogen design.http://europepmc.org/articles/PMC3463516?pdf=render
spellingShingle Rajesh Ringe
Lipsa Das
Ipsita Choudhary
Deepak Sharma
Ramesh Paranjape
Virander Singh Chauhan
Jayanta Bhattacharya
Unique C2V3 sequence in HIV-1 envelope obtained from broadly neutralizing plasma of a slow progressing patient conferred enhanced virus neutralization.
PLoS ONE
title Unique C2V3 sequence in HIV-1 envelope obtained from broadly neutralizing plasma of a slow progressing patient conferred enhanced virus neutralization.
title_full Unique C2V3 sequence in HIV-1 envelope obtained from broadly neutralizing plasma of a slow progressing patient conferred enhanced virus neutralization.
title_fullStr Unique C2V3 sequence in HIV-1 envelope obtained from broadly neutralizing plasma of a slow progressing patient conferred enhanced virus neutralization.
title_full_unstemmed Unique C2V3 sequence in HIV-1 envelope obtained from broadly neutralizing plasma of a slow progressing patient conferred enhanced virus neutralization.
title_short Unique C2V3 sequence in HIV-1 envelope obtained from broadly neutralizing plasma of a slow progressing patient conferred enhanced virus neutralization.
title_sort unique c2v3 sequence in hiv 1 envelope obtained from broadly neutralizing plasma of a slow progressing patient conferred enhanced virus neutralization
url http://europepmc.org/articles/PMC3463516?pdf=render
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