Human erythrocyte glycolipids promote HIV-1 envelope glycoprotein-mediated fusion of CD4+ cells.
We examined the role of target membrane glycolipids in CD4-mediated HIV-1 fusion by altering the glycolipid levels in CD4+ cells. CD4+ human cells exhibited 50% reduction in extent of fusion with gp120-gp41 expressing cells (TF228) when grown in the presence of a glycolipid synthesis inhibitor PPMP. We added erythrocyte glycolipids (GL) to fusion-incompetent CD4+ non-human cells by influenza-hemagglutinin-mediated fusion between GL-containing liposomes and target cells. Human erythrocyte GL (HuGL)-modified CD4+ non-human cells became susceptible to fusion with TF228 cells. Transfer of bovine erythrocyte glycolipids (BoGL) to CD4+ non-human cells under similar conditions did not complement HIV-1 fusion. Furthermore, addition of HuGL, but not BoGL, to PPMP-inhibited cells rescued fusion to the original levels. Our observations demonstrate that human erythrocyte glycolipids promote CD4-mediated HIV-1 fusion and certain glycolipid(s) from human erythrocytes may serve as alternative and/or additional cofactors in HIV-1 entry.
Puri
A
A
Section on Membrane Structure and Function, NCI-FCRDC, Frederick, Maryland 21702-1201, USA.
Hug
P
P
Muñoz-Barroso
I
I
Blumenthal
R
R
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D002459:Cell Fusion / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects*; D004912:Erythrocytes / Q000737:chemistry; D015686:Gene Products, env / Q000494:pharmacology*; D006017:Glycolipids / Q000494:pharmacology*; D015699:HIV Envelope Protein gp120 / Q000494:pharmacology; D015700:HIV Envelope Protein gp41 / Q000494:pharmacology; D015497:HIV-1 / Q000254:growth & development*; D006801:Humans; D008561:Membrane Fusion / Q000187:drug effects*; D013045:Species Specificity
D015686:Gene Products, env; D006017:Glycolipids; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41