| RRC ID |
69799
|
| 著者 |
Rawat SS, Gallo SA, Eaton J, Martin TD, Ablan S, KewalRamani VN, Wang JM, Blumenthal R, Puri A.
|
| タイトル |
Elevated expression of GM3 in receptor-bearing targets confers resistance to human immunodeficiency virus type 1 fusion.
|
| ジャーナル |
J Virol
|
| 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 host cells may escape viral infections.
|
| 巻・号 |
78(14)
|
| ページ |
7360-8
|
| 公開日 |
2004-7-1
|
| DOI |
10.1128/JVI.78.14.7360-7368.2004
|
| PII |
78/14/7360
|
| PMID |
15220409
|
| PMC |
PMC434090
|
| MeSH |
Animals
CD4 Antigens / metabolism
Cell Line, Tumor
G(M3) Ganglioside / metabolism*
G(M3) Ganglioside / pharmacology
Gene Products, env / metabolism
HIV-1 / pathogenicity*
HIV-2 / pathogenicity
HeLa Cells
Humans
Membrane Fusion / drug effects*
Mice
NIH 3T3 Cells
Receptors, HIV / chemistry
Receptors, HIV / metabolism*
Simian Immunodeficiency Virus / pathogenicity
|
| IF |
4.501
|
| リソース情報 |
| ヒト・動物細胞 |
GM95(RCB1026) |
