Viral diversity in congenital cytomegalovirus infection

描述（由申请人提供）：先天性CMV（CCMV）是最常见的先天性感染，在美国所有活产婴儿中发生率为0.5%-1.0%。据估计，所有儿童听力损失中有25%-40%是由宫内CMV感染引起的。大多数先天性CMV感染的婴儿（约90%）在出生时没有可检测到的临床异常（无症状感染），这些儿童中约有10%发展为SNHL。近一半患有CMV相关SNHL的儿童在出生时听力正常，并在语言发育的关键阶段出现听力障碍。CCMV相关SNHL的发病机制知之甚少，目前尚无针对所有CCMV感染患者的既定治疗方法。发生多种病毒株的感染，但最近的数据显示，CMV株在宿主内的变异性与RNA病毒相同。由于儿童CCMV携带大量病毒多年，我们假设多样性可能是由高水平的病毒复制产生的，较高的病毒多样性导致这种感染的不良后果。本建议的目的是确定在一个大的，明确定义的先天性CMV感染的儿童人群中，所有脱落区室中CMV毒株的多样性。我们还将研究改变病毒复制的因素的影响;免疫反应和抗病毒治疗，随着时间的推移对病毒种群的变化。通过确定病毒多样性在CCMV感染中的总体意义，并进一步确定选择压力如何影响多样性和随后的后遗症，我们将能够确定SNHL的相关性，并设计更好的抗病毒药物，以改善CCMV婴儿的长期结局。

DESCRIPTION (provided by applicant): Congenital CMV (CCMV) is the most common congenital infection occurring in 0.5% -1.0% of all live born infants in the U.S. It is estimated tat between 25% and 40% of all childhood hearing loss is caused by intrauterine CMV infection. Most infants (~90%) with congenital CMV infection have no detectable clinical abnormalities at birth (asymptomatic infection), and about 10% of these children develop SNHL. Nearly half of children with CMV-associated SNHL have normal hearing at birth and develop hearing deficits during critical stages of language development. The pathogenesis of CCMV-related SNHL is poorly understood and there is currently no established therapy for all patients with CCMV infection. Infection with multiple virus strains occurs but recent data has revealed that the variability of CMV strains within a host equals that of RNA viruses. As children with CCMV harbor large amounts of virus for many years, we hypothesize that diversity is likely generated by high levels of virus replication and higher viral diversity leads to adverse outcome in this infection. The purpose of this proposal is to define the diversity of CMV strains in all compartments of shedding in a large, well defined population of children with congenital CMV infection. We will also examine the effects of factors that alter viral replication; the immune response and antiviral therapy, on changes in viral populations over time. By determining the overall significance of viral diversity in CCMV infection, and further defining how selective pressures affect diversity and subsequent sequelae, we will then be able to define correlates of SNHL and design better anti-virals to improve long term outcomes in infants with CCMV.