ABSTRACT
INTRODUCTION: Chemokine receptor expression by human trophoblast and other placental cells have important implications for understanding the regulation of placental growth, development, and their role in maternofetal HIV transmission. CXCR7, now a deorphanized G protein coupled receptor that has been recently shown to bind to the ligands ITAC and CXCL12 has been proposed to act as a co-receptor for HIV-1, HIV-2, and SIV strains. The differential expression of CXCR7 in the human placenta is not yet reported. METHODS: The expression of CXCR7 was studied in 45 different human placental tissues, of which 20 were from early placental tissues (8-10 week old) obtained from medically terminated pregnancies and 25 were placenta from normal term deliveries. RESULTS: Immunohistochemistry and RT-PCR analysis revealed a greater expression of CXCR7 in term human placenta as compared to the early stage. This was further confirmed by real-time PCR. CONCLUSION: Our study reveals, for the first time, the differential expression of CXCR7 in early (8-10 weeks) and term human placenta. The precise role of CXCR7 in the human placenta needs to be determined. HIV vertical transmission is reported to occur mainly during the end stages of pregnancy. Our finding of increased CXCR7 expression in the term human placenta therefore warrants future studies to assess its role in the vertical transmission of HIV-1.
Subject(s)
HIV Infections/immunology , HIV/immunology , Infectious Disease Transmission, Vertical , Placenta/metabolism , Receptors, CXCR/metabolism , Chemokine CXCL12/immunology , Chemokine CXCL12/metabolism , Female , Gene Expression Regulation, Developmental/immunology , HIV/pathogenicity , HIV Infections/transmission , Humans , Placenta/immunology , Placenta/pathology , Pregnancy , Receptors, CXCR/genetics , Receptors, CXCR/immunology , Time FactorsABSTRACT
A single nucleotide polymorphism (SNP) in SDF-1, the natural ligand for the HIV-1 coreceptor CXCR4, is implicated to have protective effects against HIV-1 infection. Dendritic cells are the first to encounter HIV-1 at mucosal sites and virus binding occurs via receptors known as DC-SIGN. Variations in the number of repeats in the neck region of DC-SIGN and DC-SIGNR are reported to possibly influence host susceptibility to HIV-1 infection. We examined the SNP of SDF1-3'A by PCR-restriction fragment length polymorphism (RFLP) and repeat region polymorphisms in DC-SIGN and DC SIGNR by PCR in healthy HIV seronegative individuals, high risk STD patients seronegative for HIV, and HIV-1 seropositive patients from northern India. The detected polymorphisms were confirmed by cloning and sequencing. The genotypic frequency of SDF1-3'A/SDF1-3'A in the 100 HIV-seronegative healthy individuals, 150 HIV seronegative STD patients, and 100 HIV-1 seropositive patients were 4%, 18% and 7%, respectively. A significantly higher frequency of SDF1-3'A/SDF1-3'A was observed in high risk STD patients as compared to HIV seropositive (p=0.014) and healthy HIV-1 seronegative tested individuals (p=0.001), suggesting a protective role of SDF1-3'A in HIV-1 infection. DC-SIGN polymorphism was rare and genotype 7/7 was predominant in all groups studied. DC-SIGNR was highly polymorphic and 11 genotypes were observed among the different study groups. The precise role of the polymorphic variants of DC-SIGNR needs to be elucidated in the population.
Subject(s)
Asian People/genetics , Cell Adhesion Molecules/genetics , Chemokine CXCL12/genetics , HIV Infections/genetics , Lectins, C-Type/genetics , Polymorphism, Genetic , Receptors, Cell Surface/genetics , Adolescent , Adult , Female , Gene Frequency , Genetic Predisposition to Disease , HIV Infections/epidemiology , HIV Infections/ethnology , HIV Infections/virology , HIV Seronegativity/genetics , HIV-1 , Humans , India/epidemiology , Male , Middle Aged , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Risk , Sexually Transmitted Diseases/genetics , Young AdultABSTRACT
Host genetic factors play an important role in susceptibility to HIV-1 infection and progression to AIDS. Mutations in genes encoding chemokine receptors and their ligands, viz., CCR5delta32, CCR2-64I and SDF1-3'A are implicated to have protective effects against HIV-1 infection and/or disease progression. The distribution of these gene polymorphisms and their role in the course of the disease varies between individuals of different racial, ethnic and risk groups. We have examined the allelic frequencies of CCR5delta32, CCR2-64I and SDF1-3'A in 500 healthy North Indians tested seronegative for HIV-1, by PCR-RFLP. The plasma levels of stromal derived factor (SDF-1) protein were estimated in 75 individuals using ELISA kit. Frequencies of CCR5delta32, CCR2-64I and SDF1-3'A alleles in 500 individuals were 1.5%, 9.1% and 20.4%, respectively. The SDF1-3'A homozygosity was confirmed by PCR product cloning and sequencing. The relative hazard values calculated on the basis of the three locus genotype of each individual revealed high relative hazard values (>0.9). The plasma levels of SDF-1 ranged from 1.77 to 3.42 ng/ml and were comparable between the three genotypes of SDF-1. This is the first study to assess the plasma level of SDF-1 protein in Asian Indians. Low frequency of the protective allele CCR5delta32 observed in this study suggests high vulnerability of North Indians to HIV-1 infection. The precise role of SDF1-3'A in HIV-1 infection needs to be elucidated.
