Vertical transmission of HIV: Possible mechanisms and placental responses

Abstract

Summary Most studies to date indicate that the most frequent mode of vertical infection of HIV is transplacentally after hematogenous infection. Since virus is not reaching the fetus in about 70 per cent of the cases a strong defense system may exist. Based upon macroscopic and light microscopic examinations of the human placenta, responses to HIV infection are minimal however, the presence of the virus in most cases can be demonstrated in fetal placental monocytes (Hofbauer cells) and oftern in the trophoblastic cells. Virus presence in other cell types is reported less frequently. Infection of the trophoblastic cells appears possible both with free virus attaching to CD4 receptors, via virus-antibody complexes, and via maternal leukocytes attaching to trophoblastic cells. In vitro evidence further suggests that trophoblastic cells may both secrete free virus and deliver to CD4 positive lymphocytes. Trophoblast infection with HIV seems to be non-lytic but productive and the penetration further into the fetal tissue likely occurs via infection of Hofbauer cells. The trophoblastic cells are capable of producing both alpha, beta, and gamma interferon, in particular, during the first trimester. Their role(s) in placental response to HIV is under study. Maternal antibodies to HIV may enhance trophoblastic cell uptake of HIV. Furthermore, the maternal cellular cytotoxic immunune response to infected trophoblastic cells seems muted by unknown factor(s). Cytokines may play a central role in placental responses to HIV and external modification of placental defenses should include attempts to modify transmission to the fetus during pregnancy.