PT  - JOURNAL ARTICLE
AU  - Rawat, Satinder S.
AU  - Gallo, Stephen A.
AU  - Eaton, Julie
AU  - Martin, Thomas D.
AU  - Ablan, Sherimay
AU  - KewalRamani, Vineet N.
AU  - Wang, Ji Ming
AU  - Blumenthal, Robert
AU  - Puri, Anu
TI  - Elevated Expression of GM3 in Receptor-Bearing Targets Confers Resistance to Human Immunodeficiency Virus Type 1 Fusion
AID  - 10.1128/JVI.78.14.7360-7368.2004
DP  - 2004 Jul 15
TA  - Journal of Virology
PG  - 7360--7368
VI  - 78
IP  - 14
4099  - http://jvi.asm.org/content/78/14/7360.short
4100  - http://jvi.asm.org/content/78/14/7360.full
SO  - J. Virol.2004 Jul 15; 78
AB  - 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 Ca2+ fluxes mediated by the CXCR4 ligand SDF-1α and the CCR5 ligand MIP-1β. 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 host cells may escape viral infections.