Cytomegalovirus Transmission in Pregnant Women

描述（由申请人提供）：本提案的目的是为Beth Marshall博士提供强大的指导经验和教学培训，使她有机会实现成为学术机构独立研究员的长期目标。为此，我们提出了一个多方面的职业发展计划，包括：1)通过课程作业和研讨会的教学指导；2)广泛的指导，包括2名监督导师和6人职业咨询委员会；3)通过实质性和全面的临床研究项目进行研究训练。我们提出的研究将检验这样一种假设，即怀孕前一年或一年以上感染巨细胞病毒（血清阳性）的孕妇不能完全避免分娩同型感染的婴儿，因为她们在怀孕前或怀孕期间再次感染巨细胞病毒。胎儿巨细胞病毒（CMV）感染导致每年大约8000名新生儿智力迟钝和/或失聪。这些影响主要是由于怀孕期间母体原发性巨细胞病毒感染。虽然不太常见，但血清阳性的妇女也可以生下先天性感染的婴儿，但尚不清楚这些妇女是否持续了巨细胞病毒的再激活或再次感染了另一株。这个问题的答案对疫苗开发和干预策略都具有重要意义。为了确定再次感染是否是血清阳性妇女先天性感染的主要来源，我们将比较三组血清阳性孕妇的先天性感染率：有儿童CMV脱落的妇女、没有儿童CMV脱落的妇女和妊娠前血清转化的妇女。再感染将通过证明年长的兄弟姐妹（在研究过程中感染）和新生儿传播的病毒具有相同的基因组模式来定义。此外，我们将建立免疫反应和病毒学方面的血清阳性妇女生下受感染的新生儿，因为这些信息是重要的了解病毒传播给胎儿的因素，并最终开发有效的疫苗，以防止先天性巨细胞病毒。

DESCRIPTION (provided by applicant): The purpose of this proposal is to provide a strong mentoring experience and didactic training to afford Dr. Beth Marshall the opportunity to attain her long term goal of becoming an independent investigator in an academic institution. To this end, we propose a multifaceted career development program consisting of: 1) didactic instruction via coursework and seminar attendance; 2) extensive mentoring in the form of 2 overseeing mentors and a 6-member Career Advisory Committee; 3) research training via a substantial and well-rounded clinical research project. The research we propose will test the hypothesis that pregnant women who have been infected with CMV one or more years prior to pregnancy (seropositive) are not completely protected against delivering congenially infected infants because they become reinfected with CMV just before or during pregnancy. Infection of the fetus with cytomegalovirus (CMV) results in approximately 8,000 infants born each year who will be mentally retarded and/or deaf. These effects are mainly due to primary maternal CMV infection during pregnancy. Although less common, seropositive women can also give birth to congenially infected infants, but what is not known is whether these women have sustained a reactivation of CMV or reinfection with another strain. The answer to this question has significant implications for both vaccine development as well as intervention strategies. To determine whether reinfection is the primary source of congenital infection in seropositive women, we will compare congenital infection rates in 3 groups of seropositive pregnant women: women with children shedding CMV, women without children shedding CMV, and women who have seroconverted just prior to pregnancy. Reinfection will be defined by demonstrating identical genomic patterns of virus shed by an older sibling (infected during the course of the study) and the newborn. Additionally, we will establish the immunologic responses and virologic aspects of those seropositive women who give birth to infected newborns, as this information is important for understanding the factors involved in the transmission of virus to the fetus, and ultimately for the development of an efficacious vaccine to prevent congenital CMV.