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

BJOG. 2017 May;124(6):920-928. doi: 10.1111/1471-0528.14311. Epub 2016 Oct 3.

Abstract

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.

Keywords: HAART; HIV; CCR5; CD4; ICAM-2; chemokine receptor 5; mother-to-child transmission; pre-eclampsia; trophoblast.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Antigens, CD / metabolism
  • CD4 Antigens / metabolism
  • Cell Adhesion Molecules / metabolism
  • Cross-Sectional Studies
  • Female
  • HIV Core Protein p24 / metabolism
  • HIV Infections / complications
  • HIV Infections / transmission*
  • HIV Infections / virology
  • HIV-1 / metabolism*
  • Humans
  • Infectious Disease Transmission, Vertical*
  • Placenta / metabolism
  • Placenta / virology*
  • Pre-Eclampsia / virology*
  • Pregnancy
  • Pregnancy Complications, Infectious / virology*
  • Receptors, CCR5 / metabolism
  • Retrospective Studies
  • South Africa
  • Trophoblasts / metabolism*
  • Trophoblasts / virology
  • Young Adult

Substances

  • Antigens, CD
  • CCR5 protein, human
  • CD4 Antigens
  • Cell Adhesion Molecules
  • HIV Core Protein p24
  • ICAM2 protein, human
  • Receptors, CCR5