The role of glycosphingolipids in HIV/AIDS

Much remains unknown about basic aspects of HIV-1 Infection and cell susceptibility. Glycosphingolipid (GSL) binding by the HIV-1 adhesin gp120 has long been implicated in the Infection of non-lymphoid cells, as well as CD4(+) T cells and monocytes, the primary targets of HIV-1 Infection. We have identified the P(k) blood group antigen (a GSL) globotriaosylceramide (Gb(3)) as a new resistance effector against HIV-1 Infection. Significantly, the α-galactosyltransferase (A4GALT, Gb(3) synthase) responsible for the synthesis of Gb(3) is included among markers genetically linked to HIV-1 resistance. Other GSLs, including GalCer and GM3, have been implicated as facilitators of HIV Infection. This review will address the role of GSLs in HIV/AIDS but focus on the role of Gb(3) as a newly described natural resistance factor for the prevention of HIV Infection and examine potential therapies that would utilize soluble analogues of this unique GSL.