Sperm as infection-potentiating cofactors in HIV transmission

In this paper I will discuss the possible role of sperm as cofactors in the genital-mucosal transmission of HIV. The ideas involved arose from my laboratory's discovery that sperm bind to HLA-DR molecules expressed on somatic cells, and from our subsequent findings that lymphocytes are activated by these interactions. Sperm binding to HLA-DR mimics one of the two ligand binding characteristics of superantigens, which also bind to T-cell receptors in a V-beta-specific fashion. This property of sperm may be significant in HIV transmission because: (a) HLA-DR plays a central role in immune recognition and response; and (b) cell interactions involving HLA-DR are involved in HIV infection and disease development. After sexual contact, sperm elicit a transient leukocytic infiltration of the mammalian cervix (Thompson, L.A., Barratt, C.L., Bolton, A.E., Cooke, I.D., 1992. The leukocytic reaction of the human cervix. Am. J. Reprod. Immunol. 28, 85; Pandya, I.J., Cohen, J., 1985. The leukocytic reaction of the human uterine cervix to sperm. Fertil. Steril. 43, 417), and human cervical cells are bound and penetrated by sperm at this time (Sievers-Altermann, R., Engelbrecht, D.V., 1990. Entry of spermatozoa into the cervical mucosa and transmission of the AIDS virus. S. Afr. Med. J. 77, 319). At present, little is known about these in vivo events, but sperm-somatic cell interactions in vitro are also followed by sperm entry into the target cell cytoplasm and target cell activation. When the target cells are leukocytes, sperm interactions increase their susceptibility to HIV infection. If similar interactions occur in the cervicovaginal environment after sexual contact, they are likely to enhance the genital-mucosal transfer of HIV from semen.