LTR VARIATION REGULATES EIA EXPRESSION IN MACROPHAGES

描述(改编自调查人员摘要)：假设 这项研究是EIAV高变区的变化 Ltr增强子是EIAV毒力的主要决定因素，直接 负责调节EIAV在马巨噬细胞中的复制。 总体目标是了解增强子的可变性如何调节 急性或复发性病毒感染中的巨噬细胞复制和 慢性无症状“潜伏”感染/病毒抑制。 具体地说，PI希望确定是否存在高度变异性 Ltr可降低巨噬细胞特异性病毒的表达和 促进从有症状的EIAV感染进展到无症状的EIAV感染。 为此，PI寻求(1)识别LTR增强子序列 病毒在巨噬细胞、原代成纤维细胞和 用凝胶电泳法建立成纤维细胞样细胞系 检测(EMSA)和瞬时表达检测；(2)确定 由此确定的增强子日期基序调控EIAV在 感染性分子克隆的背景；(3)确定 EIAV LTR增强子的高度变异性控制细胞嗜性；和(4) 为了确定EIAV LTR增强子中的超变异性是否决定了 病毒在马体内的持久性或毒力。

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.