HIV-1-induced perturbations of glycosphingolipid metabolism are cell-specific and can be detected at early stages of HIV-1 infection.

Abstract

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.