Analysis of trans-placental HIV infection

在日本，艾滋病毒感染母亲围产期护理的最新进展使垂直传播率降至2%。然而，HIV经胎盘感染的机制仍是一个谜，且无法控制。本研究描述了HIV感染母亲的胎盘病理，以探讨先天性HIV感染的病理生理学和可能的胎盘屏障的形态基础。所有病例均为临产前择期剖宫产。12例患者中有11例口服AZT。分娩的新生儿没有表现出先天性感染的证据。采用HE染色、原位末端标记法和免疫组织化学方法检测胎盘组织。分别识别绒毛滋养层细胞(VT)、绒毛外滋养层细胞(EVT)和霍夫鲍尔细胞(HOB)的抗EGF-R、erb-B2和CD11b包被的MACs分离出胎盘细胞的各种成分。RT-PCR法检测HIVgp120RNA的表达。结果常规组织学检查发现，HIV感染者胎盘组织中间质炎症和细胞凋亡的发生率明显增加。通过TUNEL染色定量分析，我们观察到细胞凋亡分数的增加。免疫组织化学染色显示12例胎盘中有2例HIVp24抗原阳性。P24在室上性心动过速和室上性心动过速均有定位。利用抗原分离的胎盘细胞，我们在VT、EVT和HOB中都检测到了HIV gp120 RNA。结论以前的报道表明胎盘屏障可能解释了HIV从感染母亲传播率低的原因，但我们认为可能是胎盘后屏障保护了HIV从感染胎盘向胎儿的垂直传播。

Recent advances in perinatal care for HIV infected mothers decreased vertical transmission rates as low as 2% in Japan. However the mechanism of transplacental infection of HIV is still enigmatic and uncontrollable. In this study, we described placental pathology in HIV infected mothers in order to examine patho-physiology of congenital HIV infection and morphological basis of possible placental barriers.Subjects and methods Twelve placental samples were obtained from HIV infected mothers by AIDS working group of Japan. All cases were delivered by elective caesarean section before onset of labour. Eleven of 12 patients received oral AZT administration. No neonates delivered showed evidence of congenital infection. We examined placentae by HE stain, TUNEL and immunohistochemiistry. Various components of placental cells were separated by MACS coated with anti EGF-R, erb-B2 and CD11b which recognize villous trophoblasts (VT), extravillos trophoblasts (EVT) and Hofbauer cells (Hob) respectively. Presence of HIVgp120 RNA was examined by RT-PCR.Results By routine histological study, we observed increased frequency of intervillitis and apoptosis in placentae delivered from HIV infected patients. By quantitative analysis using TUNEL stain, we observed increased numbers of apoptotic scores. Immunohistochemical stain revealed presence of HIV p24 antigen in 2 of 12 placentae. P24 was localized both in VT and Hob. Using antigenically separated placental cells, we detected HIV gp120 RNA both in VT, EVT and Hob.Conclusion Previous reports suggest possible placental barrier to explain low transmission rates of HIV from infected mothers However we suggest, possible postplacental barriers which protect vertical transmission of HIV from infected placentae to fetuses.