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HIV Tat represses HLA-G expression in human trophoblasts.


Int Conf AIDS. 1996 Jul 7-12;11(Program Supplement):23 (abstract no.

Objective: To determine the effect of HIV Tat protein on trophoblast HLA-G expression in vitro. Methods: Transient transfections were performed on JEG human choriocarcinoma cells which are known to express the HLA-G molecule. JEG cells are grown to 1x10(6) cells per 60 mm petri dish. We co-transfected 1,2, and 3 micrograms of the eukaryotic expression vector containing the two exon HIV-Tat insert along with 5 micrograms of a construct containing the -200 bp HLA-G promoter attached to a beta-galactosidase reporter gene. Transfected cells were harvested after 72 hrs to determine their quantitative beta-galactosidase activity by measuring the chemiluminescent reaction with a single photon monitor (Boehringer Mannheim; beta-Gal Reporter Gene Assay). To demonstrate that our plasmid produces the HIV-Tat protein, we co-transfected 5 micrograms of an HIV-1 LTR linked to a CAT reporter gene (pBennCAT) with 1,2, and 3 micrograms of pcTAT DNA. Chloramphenical actyltransferase CAT) enzymatic assays were performed to quantitatively measure the actual amount of CAT protein synthesized (Boehringer Mannheim; CAT ELISA). Transfection efficiency was normalized by using beta-galactosidase gene driven by the CMV promoter. Results: The two exon HIV-Tat insert plasmid yielded up to a 18-fold high CAT activities over the non-Tat expressing plasmid during co-transfection with the HIV-1 LTR construct. Our construct containing the two exon HIV-Tat insert demonstrated a two to three fold decrease in HLA-G promoter expression during co-transfections. Our results are normalized to the parental vector that does not contain the HIV-Tat insert. Conclusion: While the Tat protein is known to stimulate HIV transcription, many other aspects of Tat have been recognized, including the suppression of MHC class I transcription. A sub-population of trophoblasts that invade the maternal tissue during pregnancy express high levels of the HLA-G molecule. Our co-transfection experiments suggest that the HIV-Tat protein can suppress HLA-G expression in vitro. HIV-Tat suppression of HLA-G appears to be mediated through the proximal 200 bp promoter region. Suppression of HLA-G transcription in trophoblasts may disturb the placental immunology resulting in adverse effects on the outcome of pregnancy. Since maternal HIV-1 infection has been indicated as a cause of miscarriage, the study of HLA-G expression during HIV-1 infection can provide a useful model for understanding maternal-fetal immunology of HIV-1 related miscarriage.

*Genes, tat *HIV-1/GENETICS *HLA Antigens/IMMUNOLOGY *Histocompatibility Antigens Class I/IMMUNOLOGY *Trophoblast/IMMUNOLOGY


Information in this article was accurate in September 30, 1997. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.