Structure–function analysis and mathematical modeling reveal insight into the mechanisms through which conserved HIV-1 gp120 epitopes are masked in the HIV-1 envelope trimer

Alexandra Trkola

Anders Krarup

Anna-Katharina Ehlert

Arthos

Bontjer

Bunnik

Carsten Magnus

Chackerian

Chen

Ching

Chohan

Cicala

Cole

Derdeyn

Diskin

Finzi

Frost

Gorny

Harrington

Huang

Huldrych F. Günthard

Jacqueline Weber

Johnson

Kitrinos

Kong

Krachmarov

Kwong

Laakso

Losman

Magnus

Masciotra

Moore

Morikita

Oliver F. Brandenberg

Palmer

Pancera

Pastore

Peter Rusert

Pinter

Pugach

Rieder

Ritola

Roland R. Regoes

Ruprecht

Rusert

Sagar

Sanders

Saunders

Schoeni-Affolter

Shibata

Shioda

Stamatatos

Sullivan

Trkola

Walker

White

Wyatt

Xiang

Zanetti

Zhou

English

PubMed

Crossref

Interaction of the gp120 V1V2 loop with a neighboring gp120 unit shields the HIV envelope trimer against cross-neutralizing antibodies

The HIV-1 envelope trimer adopts a quaternary conformation that effectively shields neutralization-sensitive domains and thus represents a major obstacle for natural and vaccine-elicited antibody responses. By using a structure-function analysis based on a specifically devised mathematical model, we demonstrate in this study that protection from neutralization is enforced by intersubunit contact between the variable loops 1 and 2 (V1V2) and domains of neighboring gp120 subunits in the trimer encompassing the V3 loop. Our data are consistent with an interaction of the V1V2 and V3 loop at the spike apex as proposed by cryoelectron tomography experiments. By defining the orientation of the V1V2 loop within the trimer toward the neighboring gp120 subunit's V3 loop, our data close an important gap in the understanding of the architecture of the trimeric spike. Knowledge on how the V1V2 barrier functions in the context of the trimer to mask conserved epitopes on gp120 may aid future vaccine design

Rusert, P

Krarup, A

Magnus, C

Brandenberg, O F

Weber, J

Ehlert, A K

Regoes, R R

Günthard, H F

Trkola, A

ZORA

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http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3135368

Interaction of the gp120 V1V2 loop with a neighboring gp120 unit shields the HIV envelope trimer against cross-neutralizing antibodies

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