BF Haynes

DR Burton

G Chuang

I Georgiev

J Gorman

JR Mascola

JS McLellan

M Bonsignori

M Pancera

NA Doria-Rose

PD Kwong

RP Staupe

S O'Dell

WC Koff

Retrovirology

English

Crossref

ORAL PRESENTATION Open AccessA short segment in the HIV-1 gp120 V1/V2 regionis a major determinant of neutralizationresistance to PG9-like antibodiesNA Doria-Rose1*, I Georgiev1, RP Staupe1, S O’Dell1, G Chuang1, J Gorman1, JS McLellan1, M Pancera1,M Bonsignori2, BF Haynes2, DR Burton3, WC Koff4, PD Kwong1, JR Mascola1From AIDS Vaccine 2012Boston, MA, USA. 9-12 September 2012BackgroundAntibody PG9 is a prototypical member of a class ofV1/V2-directed antibodies that effectively neutralizesdiverse strains of HIV-1. The crystal structure of PG9bound to scaffolded V1/V2 has provided insight into itsmode of recognition. We sought to gain a more com-plete understanding of the interaction of PG9 with thefunctional viral spike, and to extend our understandingto other antibodies of this class.MethodsWe analyzed amino acid frequencies in the V2 region ofPG9 sensitive and resistant strains to identify potentiallyimportant residues. We also used the crystal structureof PG9 with scaffolded V1/V2 to identify potential con-tact sites. Based on these analyses we designed muta-tions in PG9 resistant strains with the goal of “knockingin” sensitivity. Parent and mutant Envs were used tomake pseudoviruses. The potency of PG9 as well as V1/V2 antibodies PG16, CH01, CH04, PGT141, andPGT145 against the pseudoviruses was assessed byTZM-bl neutralization assay.ResultsFor 20/20 of resistant strains, mutations in a short seg-ment of V1/V2 resulted in gain of sensitivity to at leastone antibody of the PG9 class, and 13/20 showed gainof sensitivity to 3 or more. Mutations in V2 strand C,particularly the addition or substitution of lysine at posi-tions 168, 169, or 171, had the greatest effects.ConclusionThese results highlight the importance of strand C con-tacts for neutralization by V1/V2 antibodies, providefunctional confirmation of the crystal structure, and sug-gest a general mechanism of resistance to V1/V2-direc-ted broadly neutralizing antibodies.Author details1National Institutes of Health, Bethesda, MD, USA. 2Duke University, Durham,NC, USA. 3The Scripps Research Institute, La Jolla, CA, USA. 4InternationalAIDS Vaccine Initiative, New York, NY, USA.Published: 13 September 2012doi:10.1186/1742-4690-9-S2-O29Cite this article as: Doria-Rose et al.: A short segment in the HIV-1gp120 V1/V2 region is a major determinant of neutralization resistanceto PG9-like antibodies. Retrovirology 2012 9(Suppl 2):O29.Submit your next manuscript to BioMed Centraland take full advantage of: • Convenient online submission• Thorough peer review• No space constraints or color figure charges• Immediate publication on acceptance• Inclusion in PubMed, CAS, Scopus and Google Scholar• Research which is freely available for redistributionSubmit your manuscript at www.biomedcentral.com/submit1National Institutes of Health, Bethesda, MD, USAFull list of author information is available at the end of the articleDoria-Rose et al. Retrovirology 2012, 9(Suppl 2):O29http://www.retrovirology.com/content/9/S2/O29© 2012 Doria-Rose et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the CreativeCommons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, andreproduction in any medium, provided the original work is properly cited.

A short segment in the HIV-1 gp120 V1/V2 region is a major determinant of neutralization resistance to PG9-like antibodies

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A short segment in the HIV-1 gp120 V1/V2 region is a major determinant of neutralization resistance to PG9-like antibodies

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