Cytomegalovirus Transmission in Pregnant Women

描述（由申请人提供）：本提案的目的是提供强大的指导经验和教学培训，以使Beth马歇尔博士有机会实现她成为学术机构独立研究者的长期目标。为此，我们提出了一个多方面的职业发展计划，包括：1）通过课程和研讨会出席教学指导; 2）以2名监督导师和6名成员的职业咨询委员会的形式进行广泛的指导; 3）通过大量和全面的临床研究项目进行研究培训。我们提出的研究将检验这样一个假设，即在怀孕前一年或多年感染CMV的孕妇（血清阳性）并不能完全防止分娩同种感染的婴儿，因为她们在怀孕前或怀孕期间再次感染CMV。胎儿感染巨细胞病毒（CMV）导致每年约8，000名新生儿智力迟钝和/或失聪。这些影响主要是由于妊娠期间母体CMV感染所致。虽然不太常见，血清反应阳性的妇女也可以生下同类感染的婴儿，但不知道这些妇女是否持续了CMV的再激活或另一种毒株的再感染。这个问题的答案对疫苗开发和干预策略都有重要意义。为了确定再感染是否是血清阳性女性先天性感染的主要来源，我们将比较3组血清阳性孕妇的先天性感染率：有子女脱落巨细胞病毒的妇女、没有子女脱落巨细胞病毒的妇女以及在怀孕前血清转化的妇女。 通过证明年长同胞（在研究过程中感染）和新生儿散发的病毒基因组模式相同来定义再感染。此外，我们将建立那些血清反应阳性的妇女谁生下感染的新生儿的免疫反应和病毒学方面，因为这些信息是重要的了解病毒传播到胎儿的因素，并最终开发一种有效的疫苗，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.