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 alpha-galactosyltransferase (A4GALT, Gb3 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. [Discovery Medicine 11(59):303-313, April 2011]