Congenital cytomegalovirus infection: identification of factors determining vertical transmission and clinical outcome of infected neonates

新生儿先天性巨细胞病毒（CMV）感染是导致永久性残疾的最常见传染性原因。目前，还没有确定的治疗方法可用于预防新生儿CMV疾病。虽然被认为是一个全球性的临床问题，产前因素决定的垂直病毒传播从母亲到胎儿仍然是未知的。此外，它仍然知之甚少，为什么大多数感染的新生儿保持无症状，而一些显示中度或重度疾病symptoms.here，我们的目的是调查因素，可能会增加产前CMV感染的风险和新生儿CMV疾病的严重程度。利用从PRINCE队列（服务项目S1）中获得的人类样本，结合先天性CMV感染的小鼠模型，我们将确定产前挑战的作用，母亲和孩子的抗CMV T细胞应答以及病毒致病因素。使用已建立的CMV小鼠模型，我们将澄清妊娠期间的母体压力和药物摄入-可能可以避免的挑战-是否使后代更容易发展严重的早期CMV感染过程。对母体和新生儿抗原特异性T细胞的深入表征将确定其在生命早期阶段控制CMV感染中的作用。最后，与宿主免疫反应平行，我们将研究病原体本身，以确定决定其致病性和垂直传播可能性的病毒遗传因素。总之，我们打算回答悬而未决的问题，CMV感染生物学在接口的生殖，儿科，免疫学和病毒学，可以奠定基础，新的诊断或治疗方法。

Congenital infection with cytomegalovirus (CMV) in newborns is the most frequent infectious cause of permanent disabilities. Currently, there is no established therapy available to prevent neonatal CMV disease. Although recognized as a global clinical problem, prenatal factors determining vertical virus transmission from mother to foetus are still unknown. Moreover, it remains poorly understood why most infected neonates remain asymptomatic whereas some show moderate or severe disease symptoms.Here, we aim to investigate factors that could increase the risk of prenatal CMV-infection and severity of neonatal CMV disease. Utilizing human samples obtained from the PRINCE cohort (Service Project S1) in combination with a mouse model for congenital CMV infection we will determine the role of prenatal challenges, the anti-CMV T cell response of mother and child, and viral pathogenicity factors. Using an established CMV mouse model, we will clarify if maternal stress and medication intake during pregnancy - challenges which are potentially avoidable – render the offspring more prone to develop a severe course of early life CMV infection. In depth characterisation of maternal and neonatal antigen-specific T cells will define their role in control of CMV infection during the early life phase. Finally, in parallel to the host immune response we will investigate the pathogen itself to identify viral genetic factors that determine its pathogenicity and likelihood of vertical transmission. In summary, we intend to answer pending questions of CMV infection biology at the interface of reproduction, paediatrics, immunology, and virology that could lay the basis for new diagnostic or therapeutic approaches.