Clinical-immunological analysis of vertical HIV transmission employing a monkey model

大多数先天性人类免疫缺陷病毒（HIV）感染可以通过妊娠期间口服齐多夫定和分娩前选择性剖腹产来预防。然而，由于HIV宫内传播的机制尚不清楚，因此很难控制妊娠期经胎盘感染HIV。胎盘屏障在病毒感染中的作用尚不清楚。在本研究中，我们建立了一个猴先天性嵌合免疫缺陷病毒（Simian Human Chimeric Immunodeficiency Virus，SHIV）妊娠感染的猴模型，并研究了病毒的动力学、定位和组织病理学变化，两只妊娠食蟹猴接种了200组织培养感染剂量50（TCID_<50>）的高致病性猴/人免疫缺陷病毒，这对应于艾滋病的快速进展。1只猴在接种后第14天产下死胎<th>。我们在接种第18天对另一只猴进行了剖腹产<th>。这两个胎儿被认为是SHIV感染，因为从这两个动物获得的脐带血样本含有大量的HIV RNA。(2.55 PCR结果显示，两胎的脾脏、胸腺、肝脏和淋巴结中均检出SHIV RNA和前病毒DNA。显微镜检查显示两只动物的胎盘、脾脏、胸腺和淋巴结中HIVp 24染色阳性。我们首次建立了流行性艾滋病和随后宫内经胎盘感染HIV的猴模型，这可能适用于进一步研究和开发保护程序。

Most of congenital Human immunodeficiency virus (HIV) infection can be prevented by oral Zidovudine administration during pregnancy and elective caesarean section before onset of labor. However it is difficult to control transplacental HIV infection during pregnancy, because the mechanism of intrauterine transmission of HIV is not well clarified. Possible roles of placental barrier for viral infection is proposed though its molecular basis is unknown. In this study, we established a monkey model of congenital Simian Human chimeric immunodeficiency virus (SHIV) infection during pregnancy and examined viral kinetics, localization and histopathological changes.Two pregnant cynomolgus monkeys were inoculated with 200 tissue culture infectious dose 50 (TCID_<50>) of highly pathogenic simian/human immunodeficiency virus, which corresponds to rapid progression of AIDS. One monkey delivered dead fetus on the 14^<th> day after inoculation. We performed caesarean section of another monkey on the 18^<th> day of inoculation. Both fetuses were considered to be SHIV infected, because cord blood samples obtained from both animals contained considerable amounts of HIV RNA. (2.55 X10^4 copies/ml and 9.11 X10^2 copies/ml respectively) PCR revealed positive SHIV RNA and provirus DNA in spleen, thymus, liver and lymph nodes of both fetuses. Microscopic examination revealed positive staining of HIVp24 in placenta, spleen, thymus and lymph nodes of both animals. We established as the first time a monkey model of fluminant AIDS and subsequent intrauterine trasnsplacental HIV infection, which may be applicable for further investigation and development of protective procedures.