The role of trophoblast cell receptor expression in HIV-1 passage across the placenta in pre-eclampsia: an observational study.

Abstract

To compare expression of markers of HIV and associated receptors (p24, CD4, CCR5 and ICAM-2) in placentae and umbilical cords of HIV-associated and pre-eclamptic pregnancies to elucidate any association between these conditions in mother-to-child transmission. Cross-sectional immunohistochemical analysis of target receptor expression. Laboratory-based study of primigravidae attending a district hospital in South Africa. Retrospectively collected placental tissue (stratified into four groups according to HIV status of normotensive and pre-eclamptic participants (n = 20/group). Immunohistochemistry utilising CD4 (1:1), p24 (1:10), CCR5 (1:80) and ICAM-2 (1:100) antibodies was performed using light microscopy for image acquisition and analysis. Evaluate the expression of receptors on syncytiotrophoblast involved in in utero transmission of HIV. Syncytiotrophoblast was immunopositive for CD4 and CCR5 antibody with greater expression of CCR5 in HIV-positive versus HIV-negative groups (F_1,159  = 6.979, P = 0.009) and normotensive versus pre-eclamptic groups (F_1,159  = 8.803, P = 0.003). p24 was present in both placentae and umbilical cords of babies that were HIV-negative at 6 weeks. ICAM-2 immunostaining was observed in the syncytiotrophoblast across study groups and was significantly higher in the HIV-negative pre-eclamptic group (χ² (3)  = 45.3; P < 0.001). Concurrent CD4 and CCR5 receptor expression demonstrates possible in utero viral entry routes across the placental barrier. ICAM-2 expression may influence HIV passage across the placenta or restoration of risk of pre-eclampsia in HAART-treated mothers. HIV was found in fetal circulation regardless of antiretroviral treatment. Further confirmatory ultrastructural and molecular work is warranted. CD4, CCR5 and ICAM-2 on syncytiotrophoblast may facilitate HIV infection of passage across the placenta.