Loh Hwei-San, Mohd-Lila Mohd-Azmi, Abdul-Rahman Sheikh-Omar, Kiew Lik-Jun
Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor, Malaysia.
Virol J. 2006 Jun 1;3:42. doi: 10.1186/1743-422X-3-42.
Cytomegalovirus (CMV) congenital infection is the major viral cause of well-documented birth defects in human. Because CMV is species-specific, the main obstacle to developing animal models for congenital infection is the difference in placental architecture, which preludes virus transmission across the placenta. The rat placenta, resembling histologically to that of human, could therefore facilitate the study of CMV congenital infection in human.
In this report, we present clear evidences of the transplacental property of a new rat CMV (RCMV), namely ALL-03, which had been isolated from placenta and uterus of the house rat. Our study signifies the detection of infectious virus, virus particles, viral protein and DNA as well as immune response to demonstrate a natural model of acute CMV infection including the immunocompetent and immunocompromised host associated with or without pregnancy. It is characterized by a full range of CMV related clinical signs; lesions and anatomical virus distribution to uterus, placenta, embryo, fetus, neonate, lung, kidney, spleen, liver and salivary gland of the infected rats in addition to the virus-specific seroconversion. The preference of the virus for different organs mimics the situation in immunocompromised man. Most interestingly, the placenta was observed to be involved in the maternofetal infection and hence confirmed the hypothesis that the RCMV strain ALL-03 is capable to cross the placenta and infect the offsprings congenitally.
The maternal viremia leading to uterine infection which subsequently infecting to the fetus through the placenta is the most likely phenomenon of CMV vertical transmission in our study.
巨细胞病毒(CMV)先天性感染是人类有充分记录的出生缺陷的主要病毒原因。由于CMV具有种属特异性,开发先天性感染动物模型的主要障碍是胎盘结构的差异,这阻碍了病毒通过胎盘传播。大鼠胎盘在组织学上与人类胎盘相似,因此有助于研究人类CMV先天性感染。
在本报告中,我们提供了新的大鼠巨细胞病毒(RCMV)即ALL-03经胎盘传播特性的明确证据,该病毒是从家鼠的胎盘和子宫中分离出来的。我们的研究表明,检测到感染性病毒、病毒颗粒、病毒蛋白和DNA以及免疫反应,以证明急性CMV感染的自然模型,包括与妊娠相关或不相关的免疫健全和免疫受损宿主。其特征是出现一系列与CMV相关的临床症状;病变以及病毒在子宫、胎盘、胚胎、胎儿、新生儿、肺、肾、脾、肝和唾液腺中的解剖学分布,此外还有病毒特异性血清转化。该病毒对不同器官的偏好类似于免疫受损人群的情况。最有趣的是,观察到胎盘参与了母婴感染,因此证实了RCMV毒株ALL-03能够穿过胎盘并先天性感染后代的假设。
在我们的研究中,导致子宫感染并随后通过胎盘感染胎儿的母体病毒血症是CMV垂直传播最可能的现象。