Polliotti B M, Gnall-Sazenski S, Laughlin T S, Miller R K
University of Rochester, School of Medicine and Dentistry, Department of Obstetrics and Gynecology, 601 Elmwood Avenue, Rochester, NY 14642-8668, USA.
Placenta. 2002 Apr;23 Suppl A:S102-6. doi: 10.1053/plac.2002.0800.
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.
人绒毛膜促性腺激素（hCG）被认为与改变HIV阳性患者的卡波西肉瘤病变以及减少人淋巴细胞和人绒毛膜癌细胞中的HIV感染有关。hCG的这些抗HIV作用可能有助于解释HIV感染从母体到胎儿的有限传播率（未经治疗时为25%-35%）。然而，尚不清楚如此高剂量的hCG对HIV的垂直传播或无细胞HIV对人胎盘的感染是否有任何影响。我们以剂量依赖的方式研究了hCG对足月人胎盘HIV-1感染的影响。使用市售的hCG制剂，检测其在体外改变胎盘外植体感染的能力。在预孵育6小时和培养4天（暴露于HIV-1 Ba-L株24小时后的3天）期间加入Sigma hCG和ICNβ-hCG（0.1、1、10 IU/ml）以及APL hCG和Sigma及赛诺重组hCG（0.1、1、10、100 IU/ml）。使用DNA-PCR检测HIV的Gag和LTR区域来记录胎盘外植体的无细胞HIV感染情况。每个实验条件在不同的胎盘中重复进行（n=5），每个PCR扩增使用每个引物组重复进行两次（共20次）。我们的结果表明，在孵育过程中产生的hCG生理水平（0.2 IU/ml）以上，人胎盘中HIV-1感染存在剂量依赖性抑制。在使用的最高浓度（100 IU/ml）下，尿源性hCG实现了80%的HIV感染抑制，重组hCG约为50%。单独的β-hCG似乎具有与完整hCG分子相当的效力。在这项体外研究中，hCG表现出特定的抗HIV抑制特性，这不能仅仅归因于市售制剂中的尿液污染。基于hCG的循环水平及其由胎盘产生的情况，hCG的这种抑制作用在整个妊娠期可能以不同水平存在。在考虑临床应用之前，有必要了解这种抑制作用的具体机制。
