LTR VARIATION REGULATES EIA EXPRESSION IN MACROPHAGES

描述（改编自研究者摘要）： 这项研究表明，EIAV高变区的改变 LTR增强子是EIAV毒力的主要决定因素， 负责马巨噬细胞中EIAV复制的调节。 总体目标是了解增强子变异性如何调节 急性或复发性病毒血症感染中的巨噬细胞复制， 慢性无症状“潜伏”感染/病毒血症抑制。 具体而言，PI希望确定是否存在高变， LTR的发生降低巨噬细胞特异性病毒表达， 促进从有症状的EIAV感染发展为无症状的EIAV感染。 为此，PI寻求（1）鉴定LTR增强子序列 所需的病毒表达在巨噬细胞，原代成纤维细胞和 使用电泳凝胶移位建立成纤维样细胞系 检测（EMSA）和瞬时表达检测;（2）确定是否 由此鉴定的增强子Date基序调节EIAV在细胞中的复制。 感染性分子克隆的背景;（3）确定是否 EIAV LTR增强子的高变性控制细胞嗜性;和（4） 以确定EIAV LTR增强子的高变是否决定了 马体内病毒持久性或毒力。

DESCRIPTION (Adapted from investigator's abstract): The hypothesis of this study is that alterations in the hypervariable region of the EIAV LTR enhancer are a major determinant of EIAV virulence, being directly responsible for regulation of EIAV replication in equine macrophages. The overall goal is to understand how enhancer variability regulates macrophage replication in acute or relapsing viremic infection and chronic asymptomatic "latent" infection/viremic suppression. Specifically, the PI wishes to establish whether hypervariability in the LTR occurs to decrease macrophage-specific viral expression and facilitate progression from symptomatic to asymptomatic EIAV infection. To this end, the PI seeks (1) to identify LTR enhancer sequences required for viral expression in macrophages, primary fibroblasts and established fibroblastoid cell lines using electrophoretic gel shift assays (EMSAs) and transient expression assays; (2) to determine if enhancer Date motifs thus identified regulate EIAV replication in the context of an infectious molecular clone; (3) to determine if hypervariability in the EIAV LTR enhancer controls cell tropism; and (4) to determine if hypervariability in the EIAV LTR enhancer determines virus persistence or virulence in horses in vivo.