title: The role of trophoblast cell receptor expression in HIV-1 passage across the placenta in pre-eclampsia: an observational study.
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.
  
  
  METHODS
  Cross-sectional immunohistochemical analysis of target receptor expression.
  
  
  METHODS
  Laboratory-based study of primigravidae attending a district hospital in South Africa.
  
  
  METHODS
  Retrospectively collected placental tissue (stratified into four groups according to HIV status of normotensive and pre-eclamptic participants (n = 20/group).
  
  
  METHODS
  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.
  
  
  METHODS
  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).
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  CD4, CCR5 and ICAM-2 on syncytiotrophoblast may facilitate HIV infection of passage across the placenta.
authors.affiliation: School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: V
authors.initials: V
authors.lastname: Dorsamy
authors.affiliation: Optics and Imaging Centre, Doris Duke Medical Research Institute, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: C
authors.initials: C
authors.lastname: Vallen
authors.affiliation: Department of Basic Medical Sciences, Durban University of Technology, Durban, South Africa.
authors.forename: F
authors.initials: F
authors.lastname: Haffejee
authors.affiliation: Women's Health and HIV Research Unit, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: J
authors.initials: J
authors.lastname: Moodley
authors.affiliation: Optics and Imaging Centre, Doris Duke Medical Research Institute, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: T
authors.initials: T
authors.lastname: Naicker
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D003430:Cross-Sectional Studies; D005260:Female; D016655:HIV Core Protein p24 / Q000378:metabolism; D015658:HIV Infections / Q000150:complications / Q000635:transmission* / Q000821:virology; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D018445:Infectious Disease Transmission, Vertical; D010920:Placenta / Q000378:metabolism / Q000821:virology*; D011225:Pre-Eclampsia / Q000821:virology*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000821:virology*; D019713:Receptors, CCR5 / Q000378:metabolism; D012189:Retrospective Studies; D013019:South Africa; D014327:Trophoblasts / Q000378:metabolism* / Q000821:virology; D055815:Young Adult
chemical_list: D015703:Antigens, CD; C584933:CCR5 protein, human; D015704:CD4 Antigens; D015815:Cell Adhesion Molecules; D016655:HIV Core Protein p24; C065289:ICAM2 protein, human; D019713:Receptors, CCR5
keywords: 
  HAART
  ; 
  HIV
  ; CCR5; CD4; ICAM-2; chemokine receptor 5; mother-to-child transmission; pre-eclampsia; trophoblast