HIV-1 co-receptor expression on trophoblastic cells from early placentas and permissivity to infection by several HIV-1 primary isolates

Abstract

SUMMARY We examined CD4 and major HIV-1 co-receptor expression by trophoblast cells (TC) from early placentas, and the permissiveness of TC for infection by several natural HIV-1 isolates in vitro. Ten early placentas (4–6 weeks of gestation) from HIV−women were obtained after elective abortion. CD4 and HIV-1 co-receptor expression by TC was examined in terms of both mRNA and protein. The same TC were then challenged with three clinical HIV isolates of known phenotype, two originating from mothers who transmitted the virus to their child and one from a vertically infected newborn. TC infection was detected by polymerase chain reaction. CD4 expression was detected in five of the 10 placentas, while membrane protein expression of CCR3, CXCR4 and CCR5 was detected in every case, despite quantitative differences among individuals. Bonzo, GPR1 and ChemR23 mRNAs were detected in all TC preparations. TC from seven out of eight placentas were permissive to HIV entry, but no productive viral replication was detected (reverse transcriptase activity in culture supernatants). Interestingly, the addition of chemokine(s) or a CD4-blocking antibody to the cultures failed to inhibit TC virus entry. These data point to marked interindividual variability in HIV co-receptor expression by trophoblast cells and show that TC from early placentas can be infected in vitro by clinical HIV-1 isolates. They also suggest that viral entry in vitro might occur through a mechanism independent of both CD4 and chemokine receptors.