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

OBJECTIVE

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.

DESIGN

Cross-sectional immunohistochemical analysis of target receptor expression.

SETTING

Laboratory-based study of primigravidae attending a district hospital in South Africa.

POPULATION OR SAMPLE: Retrospectively collected placental tissue (stratified into four groups according to HIV status of normotensive and pre-eclamptic participants (n = 20/group).

METHOD: 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.

MAIN OUTCOME MEASURES: Evaluate the expression of receptors on syncytiotrophoblast involved in in utero transmission of HIV.

RESULTS

Syncytiotrophoblast was immunopositive for CD4 and CCR5 antibody with greater expression of CCR5 in HIV-positive versus HIV-negative groups (F1,159  = 6.979, P = 0.009) and normotensive versus pre-eclamptic groups (F1,159  = 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).

CONCLUSION

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.

TWEETABLE ABSTRACT: CD4, CCR5 and ICAM-2 on syncytiotrophoblast may facilitate HIV infection of passage across the placenta.