Inhibitory Effects of Human Chorionic Gonadotropin (hCG) Preparations on HIV Infection of Human Placenta in vitro

University of Rochester, School of Medicine and Dentistry, Department of Obstetrics and Gynecology, 601 Elmwood Avenue, Rochester, NY 14642-8668, USA.
Placenta (Impact Factor: 2.71). 05/2002; 23 Suppl A:S102-6. DOI: 10.1053/plac.2002.0800
Source: PubMed


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.

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    • "A dose-dependent inhibition of HIV infection in hCG-treated tissue explants was found [12]. Correlations were made between hCG concentrations in blood and viral load or HIV infection [12] [13]. "
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    ABSTRACT: Mononuclear phagocytes (MP; monocytes, tissue macrophages, and dendritic cells) are reservoirs, vehicles of dissemination, and targets for persistent HIV infection. However, not all MP population equally support viral growth. Such differential replication is typified by the greater ability of placental macrophages (PM), as compared to blood borne monocyte-derived macrophages (MDM), to restrict viral replication. Since cytosolic protein patterns can differentiate macrophage subtypes, we used a proteomics approach consisting of surface-enhanced laser desorption ionization time-of-flight (SELDI-TOF), tandem mass spectrometry, and Western blots to identify differences between the uninfected and HIV-infected PM and MDM protein profiles linked to viral growth. We performed proteome analysis of PM in the molecular range of 5-20kDa. We found that a SELDI-TOF protein peak with an m/z of 11,100, which was significantly lower in uninfected and HIV-infected PM than in MDM, was identified as cystatin B (CSTB). Studies of siRNA against CSTB treatment in MDM associated its expression with HIV replication. These data demonstrate that the low molecular weight placental macrophage cytosolic proteins are differentially expressed in HIV-infected PM and MDM and identify a potential role for CSTB in HIV replication. This work also serves to elucidate a mechanism by which the placenta protects the fetus from HIV transmission.
    Placenta 11/2008; 29(12):1016-23. DOI:10.1016/j.placenta.2008.09.005 · 2.71 Impact Factor
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    • "Three chorionic villi explants of 0.20 mg each, taken from the central part of cotyledons were employed for tissue culture (Fretes and Fabro, 1990a; Polliotti et al., 2002). Placental explants were washed with HanksÕs solution, pH 7.4, and afterward it was placed into a well of a 24-well plaque with 1. "
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    ABSTRACT: We hypothesize that a sustained infection of Trypanosoma cruzi into placental tissue might be diminished. Human placental chorionic villi and VERO cells as controls were co-cultured with T. cruzi. Parasites occupied 0.0137% at 3h, 0.0224% (24h), and 0.0572% (72 h) of the total chorionic villi area analyzed and some few placental samples were negative to parasite DNA, whereas 52% of VERO cells were infected at 3h and parasites occupied 0.57%, at 24h the parasite area was of 2.78% and at 72 h was of 3.32%. There were no live parasites in placenta-T. cruzi culture media at 72 h of co-culture. There were significantly increased dead parasites when T. cruzi was treated with unheated culture media coming from placental explants and fewer dead parasites when pre-heated culture media were employed. CONCLUSION: Low productive infection by T. cruzi into placental tissue associated with no viable parasites in the culture media partially due to placental thermo labile substances.
    Experimental Parasitology 11/2004; 108(3-4):176-81. DOI:10.1016/j.exppara.2004.07.013 · 1.64 Impact Factor
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    ABSTRACT: We briefly recall the architecture of the placenta and its unique function as both barrier and transport/exchange organ. We then take the example of mother to child transmission of HIV, and examine the mechanisms which are thought to account for both transmission and selection of viral variants from the mother to the fœtus.We finish by listing some of the most important virus which can cross the placenta. We conclude by stating that the placental barrier is unique, and insist on the importance of syncytiotrophoblast cells, and the limitation it poses on in vitro studies.
    Revue Française des Laboratoires 05/2003; 2003(353). DOI:10.1016/S0338-9898(03)90003-5
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