Sperm as mitogenic cofactors for HIV transmission

While studying interactions between gametes and somatic cells, we discovered that human sperm bind to HLA-DR via sperm surface structures that share antigenic epitopes with CD4. This finding has potential significance for HIV transmission, because: (i) HIV virions carry HLA-DR from infected cells; (ii) the HIV envelope glycoprotein gp160 has regions of homology with HLA-DR; and (iii) HLA-DR is a signal-transducing molecule of which the ligation triggers target-cell activation. If sperm bind to HIV by this recognition pathway, their selective binding to HLA-DR-expressing cells could deliver virus or viral antigens to muscosal cells of hematopoietic origin. For sperm not carrying virus, binding and cross-linking of HLA-DR on the same cells could trigger cell activation, thereby increasing target-cell susceptibility to HIV infection. We and others have shown that normal sperm bind to HIV in vitro, and that virus is present as nucleic acid in sperm from infected men. In the absence of virus, sperm from normal semen amplify cell activation by polyclonal mitogens or conventional antigen, and they dramatically increase the in vitro infectivity of free HIV particles. If similar events occur in the female reproductive tract after sexual contact, sperm-mediated target-cell activation may augment HIV transmission by this body fluid.