Glycans flanking the hypervariable connecting peptide between the A and B strands of the V1/V2 domain of HIV-1 gp120 confer resistance to antibodies that neutralize CRF01_AE viruses

PloS One
Sara O'RourkePhillip W Berman

Abstract

Understanding the molecular determinants of sensitivity and resistance to neutralizing antibodies is critical for the development of vaccines designed to prevent HIV infection. In this study, we used a genetic approach to characterize naturally occurring polymorphisms in the HIV envelope protein that conferred neutralization sensitivity or resistance. Libraries of closely related envelope genes, derived from virus quasi-species, were constructed from individuals infected with CRF01_AE viruses. The libraries were screened with plasma containing broadly neutralizing antibodies, and neutralization sensitive and resistant variants were selected for sequence analysis. In vitro mutagenesis allowed us to identify single amino acid changes in three individuals that conferred resistance to neutralization by these antibodies. All three mutations created N-linked glycosylation sites (two at N136 and one at N149) proximal to the hypervariable connecting peptide between the C-terminus of the A strand and the N-terminus of the B strand in the four-stranded V1/V2 domain β-sheet structure. Although N136 has previously been implicated in the binding of broadly neutralizing monoclonal antibodies, this glycosylation site appears to inhibit the bi...Continue Reading

References

Aug 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·A AshkenaziD J Capon
Sep 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·E S DaarD D Ho
Nov 25, 1988·Science·J D RobertsT A Kunkel
Feb 9, 1989·Nature·D J CaponJ E Groopman
Apr 12, 1994·Proceedings of the National Academy of Sciences of the United States of America·J P VartanianS Wain-Hobson
Mar 20, 1996·AIDS Research and Human Retroviruses·O Jarrett
Mar 18, 2000·Antimicrobial Agents and Chemotherapy·C J PetropoulosJ M Whitcomb
Aug 9, 2002·The New England Journal of Medicine·Susan J LittleDouglas D Richman
Oct 24, 2002·Acta Crystallographica. Section D, Biological Crystallography·Elizabeth PottertonMartin Noble
Mar 20, 2003·Proceedings of the National Academy of Sciences of the United States of America·Douglas D RichmanChristos J Petropoulos
Mar 21, 2003·Nature·Xiping WeiGeorge M Shaw
Feb 13, 2004·Bioinformatics·Michele ClampGeoffrey J Barton
Feb 3, 2005·The Journal of Infectious Diseases·Neil M FlynnUNKNOWN rgp120 HIV Vaccine Study Group
Nov 17, 2006·The Journal of Infectious Diseases·Punnee PitisuttithumUNKNOWN Bangkok Vaccine Evaluation Group
May 22, 2007·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Becky SchweighardtTerri Wrin
Aug 28, 2007·Nature Medicine·Yuxing LiJohn R Mascola
Nov 30, 2007·Current HIV Research·Michael B Zwick, Dennis R Burton
Mar 29, 2008·Briefings in Bioinformatics·Kazutaka Katoh, Hiroyuki Toh
Jun 14, 2008·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Martin S HirschDouglas D Richman
Oct 22, 2009·The New England Journal of Medicine·Supachai Rerks-NgarmUNKNOWN MOPH-TAVEG Investigators
Oct 30, 2009·Molecular Biology and Evolution·Marcos Pérez-LosadaPhillip W Berman
Nov 17, 2009·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Becky SchweighardtFrederick M Hecht

❮ Previous
Next ❯

Citations

Aug 12, 2016·Journal of Virology·Philip MwimanziMark A Brockman
Jun 16, 2017·Journal of Virology·Rebecca L R PowellSusan Zolla-Pazner
Dec 8, 2020·PloS One·Elma H AkandJohn M Murray

❮ Previous
Next ❯

Datasets Mentioned

BETA
JX848346-JX848351
AF033819

Methods Mentioned

BETA
Assay
glycosylation

Software Mentioned

GraphPad Prism
Jalview
MAFFT

Related Concepts

Related Feeds

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Addiction

This feed focuses mechanisms underlying addiction and addictive behaviour including heroin and opium dependence, alcohol intoxication, gambling, and tobacco addiction.

Allergy and Asthma

Allergy and asthma are inflammatory disorders that are triggered by the activation of an allergen-specific regulatory t cell. These t cells become activated when allergens are recognized by allergen-presenting cells. Here is the latest research on allergy and asthma.

Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.