HIV-1-induced perturbations of glycosphingolipid metabolism are cell-specific and can be detected at early stages of HIV-1 infection.
The metabolism of glycosphingolipids (GSL) has been investigated in peripheral blood mononuclear cells (PBMC) from 8 patients at an early stage of HIV-1 infection. Following metabolic labeling of these cells with [14C]galactose, the GSL were purified and the radioactivity incorporated into each individual GSL quantitated by phosphoimaging. Compared with PBMC from seronegative donors, the GSL metabolism in PBMC from HIV-1-infected individuals was characterized by an increased synthesis of two GSL: the B-lymphocyte differentiation antigen globotriaosylceramide (Gb3, also referred to as CD77), and the monosialoganglioside GM3, a marker of T-lymphocytes and macrophages. The accumulation of Gb3 and GM3 in PBMC from HIV-1-infected patients was associated with the appearance of anti-Gb3 and anti-GM3 antibodies. Because these GSL are involved in the control of cell proliferation and signal transduction, such anti-GSL autoantibodies may contribute to the immune suppression during the course of HIV-1 infection. Studies on purified cell populations showed that GM3 accumulation occurred preferentially in HIV-1-infected monocytes/macrophages, whereas the synthesis glucosylceramide, the common precursor of complex GSL, was enhanced in both macrophages and CD4+ lymphocytes. Taken together, our data suggest that the dysregulation of GSL metabolism is an early event of HIV-1 pathogenesis that can induce important effects on immune cells homeostasis.
Fantini
J
J
Laboratoire de Biochimie et Biologie de la Nutrition, Faculté des Sciences de St Jérôme, Marseille, France. JACQUES.FANTINI@LBBN.u-3mrs.fr
Tamalet
C
C
Hammache
D
D
Tourrès
C
C
Duclos
N
N
Yahi
N
N
D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000821:virology; D002478:Cells, Cultured; D002855:Chromatography, Thin Layer; D005260:Female; D005679:G(M3) Ganglioside / Q000302:isolation & purification / Q000378:metabolism; D006028:Glycosphingolipids / Q000302:isolation & purification / Q000378:metabolism*; D015658:HIV Infections / Q000097:blood / Q000378:metabolism*; D015497:HIV-1; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism / Q000821:virology; D008297:Male; D014281:Trihexosylceramides / Q000302:isolation & purification / Q000378:metabolism
D005679:G(M3) Ganglioside; D006028:Glycosphingolipids; D014281:Trihexosylceramides; C018549:globotriaosylceramide