Inhibitory effects of human chorionic gonadotropin (hCG) preparations on HIV infection of human placenta in vitro.
Human chorionic gonadotropin (hCG) has been implicated in modifying Kaposi sarcoma lesions in HIV positive patients and in reducing HIV infection in human lymphocytes and human choriocarcinoma cells. These anti-HIV effects of hCG may contribute to the limited maternal to fetal transmission of HIV infection (25-35 per cent without treatment). However, it is unknown whether such high dosages of hCG have any effect on vertical transmission of HIV or on the infection of the human placenta with cell-free HIV. We have investigated in a dose dependent manner the effects of hCG on HIV-1 infection of human term placentae. Using commercially available hCG preparations, the ability to modify the infection of placental explants in vitro was examined. Sigma hCG and ICN beta-hCG (0.1, 1, 10 IU/ml) and APL hCG and Sigma and Serono recombinant hCG (0.1, 1, 10, 100 IU/ml) were added during 6 h of pre-incubation and the 4 days of culture (3 days following the 24 h exposure to HIV-1 Ba-L strain). Cell-free HIV infection of the placental explants was documented using DNA-PCR detection of Gag and LTR regions of HIV. Each experimental condition was repeated in different placentae (n=5) and each PCR amplification was performed in duplicate with each primer set (total=20). Our results demonstrate that there is a dose dependent inhibition of HIV-1 infection in the human placenta above the physiologic levels (0.2 IU/ml) of hCG produced during incubation. At the highest concentration used (100 IU/ml), 80 per cent inhibition of HIV infection was achieved with urinary extract hCG and about 50 per cent with recombinant hCG. beta-hCG alone appears to possess an efficacy equivalent to the complete hCG molecule. In this in vitro study, hCG demonstrates specific anti-HIV inhibitory properties that cannot be solely attributed to urinary contamination of the commercial preparations. Such inhibitory action of hCG may be present at varying levels throughout gestation based upon the circulating levels of hCG and its production by the placenta. Knowledge of the specific mechanisms underlying this inhibition is necessary before clinical applications can be considered.
Polliotti
B M
BM
University of Rochester, School of Medicine and Dentistry, Department of Obstetrics and Gynecology, 601 Elmwood Avenue, Rochester, NY 14642-8668, USA.
Gnall-Sazenski
S
S
Laughlin
T S
TS
Miller
R K
RK
D000328:Adult; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D002824:Chorionic Villi / Q000187:drug effects* / Q000821:virology; D017931:DNA Primers / Q000737:chemistry; D004279:DNA, Viral / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D005260:Female; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D009924:Organ Culture Techniques; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011263:Pregnancy Trimester, Third; D014779:Virus Replication / Q000187:drug effects*
D006063:Chorionic Gonadotropin; D017931:DNA Primers; D004279:DNA, Viral