Purpose of review: Histo-blood group antigens belonging to the P1PK and GLOB blood group systems are involved in bacterial infections, but a substantial body of evidence is emerging that some of these glycosphingolipids play a role in HIV infection. These recent findings have raised additional questions regarding the possible role of the P/Gb3 histo-blood group antigen in HIV-1 infection.
Recent findings: Early studies implicated a number of glycosphingolipids able to interact with HIV envelope glycoprotein 120. It has been recently reported that cellular or soluble P/Gb3 histo-blood group antigen provides protection from HIV-1 infection. This resistance mechanism appears to be mediated through inhibition of fusion of the HIV-1 envelope to the cell target membrane. Protection has been shown to be provided to both HIV-1 X4 and R5 tropic strains. Indeed, an inverse correlation has been documented between the expression of P/Gb3 on the cellular membrane and susceptibility to HIV infection. Moreover, soluble P/Gb3 analogues have been shown to inhibit HIV infection.
Summary: The P/Gb3 histo-blood group antigen is the first described cell surface expressed natural resistance factor for prevention of HIV infection. Increased expression of P/Gb3 correlates to decreased HIV infection, whereas decreased or absent P/Gb3 increases HIV susceptibility. Soluble P/Gb3 analogues can inhibit HIV by two mechanisms: direct inhibition of the free virus and inhibition of viral entry. Future development of soluble P/Gb3 analogues, pharmacologic means of increasing cell surface expression of P/Gb3 on HIV susceptible target cells or both may result in novel therapeutic modalities for the prevention and eradication of HIV/AIDS.