Molecular Epidemiology of Primary CMV Infection

描述（由申请人提供）：基于基因组差异检测的分子技术显示，许多CMV毒株在人群中流行。虽然原发性人类CMV感染传统上被认为是由单一毒株引起的，但以前对CMV毒株异质性的研究主要限于器官移植受者。在这种情况之外，分离出多种CMV毒株被认为是再感染的证据。研究表明，在临床环境和社区中，受试者（移植患者、艾滋病患者、日托幼儿、性活跃者）可能会暴露于多种CMV毒株并随着时间的推移再次感染。以前没有研究确定健康受试者的初始CMV感染是否涉及多种菌株。对这一问题的兴趣源于我们以前的工作，在这些工作中，我们在因先天性CMV感染而死于子宫内的胎儿中鉴定了多种CMV毒株（基于UL 144和US 28基因型）。只有一个单一的基因型，确定从培养分离的CMV感染的活婴儿。根据文献，可以预期这些严重的先天性CMV感染病例是由于原发性母体感染所致。然而，多种菌株的检测表明，再感染可能发挥了作用。检测的差异是否与组织的直接测序有关，而不是从培养物中选择优先分离株尚不清楚。本申请的目的是通过以下具体目的来表征健康成人中原发性CMV感染期间的菌株异质性：1.根据UL 144、UL 146和糖蛋白B基因的序列多样性，确定健康成人原发性CMV感染是涉及单一毒株还是多毒株。2.确定初次感染后6至12个月内检测到的CMV毒株是否与初次感染时检测到的毒株不同。这项探索性研究将有助于确定菌株多样性可用作CMV再感染证据的程度。它可能会奠定基础，为更广泛的研究（在受试者数量，病毒排泄的网站数量，研究的基因数量）的菌株多样性在正常宿主中的原发性CMV感染。此外，这项研究将对疫苗开发和理解自然CMV感染如何导致对病毒的广泛免疫产生重要影响。PHS 398/2590（Rev. 05/01）Page 2 Continuation Format Page CMV（巨细胞病毒）感染是最常见的由母亲传染给新生儿的感染，影响全世界1%的新生儿。病毒的基因组成有几种变化，专业术语是病毒株。本申请的目的是确定急性CMV感染是由单一菌株还是多种菌株引起的，如使用基因测序技术对各种体液所确定的。这一应用将提高我们对急性CMV感染的理解，并将为疫苗开发开辟新的研究方向。.

DESCRIPTION (provided by applicant): Molecular techniques based on detection of genomic differences reveal that numerous CMV strains are circulating in the population. Although primary human CMV infection is traditionally believed to be caused by a single strain, previous studies of CMV strain heterogeneity have been limited mostly to organ transplant recipients. Outside this setting, isolation of multiple CMV strains has been considered proof of reinfection. Studies show that in both clinical settings and in the community, subjects (transplant patients, AIDS patients, young children in day care, sexually active persons) may be exposed to and re-infected over time with multiple CMV strains. No previous studies have determined whether initial CMV infection in healthy subjects involves multiple strains. Interest in this issue stems from our previous work in which we identified multiple CMV strains (based on UL144 and US28 genotypes) in fetuses who died in utero from congenital CMV infection. Only a single genotype was identified from cultured isolates of CMV infected live infants. Based on the literature, one would expect that these severe cases of congenital CMV infection were due to a primary maternal infection. However, the detection of multiple strains suggests that reinfection could have played a role. Whether the difference in detection is related to direct sequencing from tissue as opposed to selection of preferential isolates from culture is unclear. The goal of this application is to characterize strain heterogeneity during primary CMV infection in healthy adults through the following specific aims: 1. To determine whether primary CMV infection in healthy adults involves single strain or multiple strains based on sequence diversity in UL144, UL146 and glycoprotein B genes. 2. To determine whether CMV strains detected six to twelve months years after primary infection are different from the strain(s) detected at the time of initial infection. This exploratory study will help define the extent to which strain diversity can be used as evidence of CMV reinfection. It will likely lay the groundwork for a more extensive study (in terms of number of subjects, number of sites of viral excretion, number of genes studied) of strain diversity in primary CMV infection in the normal host. In addition this study will have significant implications for vaccine development and understanding how natural CMV infection leads to broad immunity to the virus. PHS 398/2590 (Rev. 05/01) Page 2 Continuation Format Page CMV (cytomegalovirus) infection is the most common infection transmitted from mothers to newborns, affecting 1 percent of newborns worldwide. There are several variations in the genetic makeup of the virus, and the professional term for those is viral strains. The goal of this application is to determine whether acute CMV infection is caused by a single strain or multiple strains, as determined using genetic sequencing techniques on a variety of bodily fluids. This application will improve our understanding of acute CMV infection and will open new research directions in vaccine development. .