Dominant-negative effect of hetero-oligomerization on the function of the human immunodeficiency virus type 1 envelope glycoprotein complex

Virology
Carolina HerreraSimon Beddows

Abstract

The human immunodeficiency virus type 1 (HIV-1) envelope (Env) glycoprotein forms trimers that mediate interactions with the CD4 receptor and a co-receptor on the target cell surface, thereby triggering viral fusion with the cell membrane. Cleavage of Env into its surface, gp120, and transmembrane, gp41, moieties is necessary for activation of its fusogenicity. Here, we produced pseudoviruses with phenotypically mixed wild-type (Wt) and mutant, cleavage-incompetent Env in order to quantify the effects of incorporating uncleaved Env on virion infectivity, antigenicity and neutralization sensitivity. We modeled the relative infectivity of three such phenotypically mixed viral strains, JR-FL, HXBc2 and a derivative of the latter, 3.2P, as a function of the relative amount of Wt Env. The data were fit very closely (R(2) > 0.99) by models which assumed that only Wt homotrimers were functional, with different approximate thresholds of critical numbers of functional trimers per virion for the three strains. We also produced 3.2P pseudoviruses containing both a cleavage-competent Env that is defective for binding the neutralizing monoclonal antibody (NAb) 2G12, and a cleavage-incompetent Env that binds 2G12. The 2G12 NAb was not able t...Continue Reading

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Citations

Sep 18, 2013·Journal of Immunological Methods·Carsten MagnusRoland R Regoes
Nov 21, 2008·Journal of Virology·Carsten MagnusRoland R Regoes
May 1, 2007·Current Opinion in HIV and AIDS·David C MontefioriJohn R Mascola
Dec 3, 2014·Virology·Melissa Zarr, Robert Siliciano
Nov 7, 2015·Trends in Microbiology·Oliver F BrandenbergAlexandra Trkola
Mar 31, 2007·Current Opinion in Structural Biology·Kenneth H Roux, Kenneth A Taylor
Sep 25, 2015·Retrovirology·Daniel J StiehRobin J Shattock
Jun 5, 2013·Biology·William J Allen, Robert C Rizzo
May 1, 2010·Viruses·Michael A LobritzEric J Arts

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