Effects of the human CD38 glycoprotein on the early stages of the HIV-1 replication cycle

CD38 displays lateral association with the HIV-1 receptor CD4. This associa tion is potentiated by the HIV-1 envelope glycoprotein gp120. The aim of th is work was to evaluate the CD38 role in T cell susceptibility to HTV-1 inf ection. Using laboratory X4 HIV-1 strains and X4 and X4/R5 primary isolates , we found that CD38 expression was negatively correlated to cell susceptib ility to infection, evaluated as percentage of infected cells, release of H N p24 in the supernatants, and cytopathogenicity. This correlation was at f irst suggested by results obtained in a panel of human CD4(+) T cell lines expressing different CD38 levels (MT-4, MT-2, C8166, CEMx174, Supt-1, and H 9) and then demonstrated using CD38 transfectants of MT-4 cells (the line w ith the lowest CD38 expression). To address whether CD38 affected viral bin ding, we used mouse T cells that are non-permissive for productive infectio n. Gene transfection in mouse SR.D10.CD4(-).F1 T cells produced four Lines expressing human CD4 and/or CD38. Ability of CD4(+)CD38(+) cells to bind HI V-1 or purified recombinant gp120 was significantly lower than that of CD4( +)CD38(-) cells. These data suggest that CD38 expression inhibits lymphocyt e susceptibility to HIV infection, probably by inhibiting gp120/CD4-depende nt viral binding to target cells.