Elevated expression of GM3 in receptor-bearing targets confers resistance to human immunodeficiency virus type 1 fusion

Journal of Virology
Satinder S RawatAnu Puri

Abstract

GM3, a major ganglioside of T lymphocytes, promotes human immunodeficiency virus type 1 (HIV-1) entry via interactions with HIV-1 receptors and the viral envelope glycoprotein (Env). Increased GM3 levels in T lymphocytes and the appearance of anti-GM3 antibodies in AIDS patients have been reported earlier. In this study, we investigated the effect of GM3 regulation on HIV-1 entry by utilizing a mouse cell line (B16F10), which expresses exceptionally high levels of GM3. Strikingly, B16 cells bearing CD4, CXCR4, and/or CCR5 were highly resistant to CD4-dependent HIV-1 Env-mediated membrane fusion. In contrast, these targets supported membrane fusion mediated by CD4-requiring HIV-2, SIV, and CD4-independent HIV-1 Envs. Coreceptor function was not impaired by GM3 overexpression as indicated by Ca(2+) fluxes mediated by the CXCR4 ligand SDF-1alpha and the CCR5 ligand MIP-1beta. Reduction in GM3 levels of B16 target cells resulted in a significant recovery of CD4-dependent HIV-1 Env-mediated fusion. We propose that GM3 in the plasma membrane blocks HIV-1 Env-mediated fusion by interfering with the lateral association of HIV-1 receptors. Our findings offer a novel mechanism of interplay between membrane lipids and receptors by which h...Continue Reading

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Citations

Mar 30, 2011·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Norman J HaugheyVeera Venkata Ratnam Bandaru
Oct 9, 2012·The Journal of Biological Chemistry·Robert BlumenthalMathias Viard
Aug 27, 2010·Current Opinion in Hematology·Donald R Branch
Feb 12, 2008·Applied and Environmental Microbiology·Prerak T DesaiBart C Weimer
Jul 25, 2006·FEBS Letters·Markus R Wenk
Mar 11, 2015·Chemical Communications : Chem Comm·Richard J FairPeter H Seeberger
Aug 27, 2010·Viruses·Abdul A Waheed, Eric O Freed
Nov 25, 2005·Bioscience Reports·Satinder S RawatAnu Puri
Aug 23, 2019·The Journal of Membrane Biology·Pranav Adhyapak, Shobhna Kapoor
Mar 29, 2019·Journal of Virology·Kelly DrewsMark Kester
Dec 20, 2014·Biological Chemistry·Jürgen Schneider-Schaulies, Sibylle Schneider-Schaulies
May 20, 2020·Frontiers in Microbiology·Amani AudiHassan Zaraket
Aug 20, 2021·Frontiers in Microbiology·Jian WangNan Yao

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