MOLECULAR ASPECTS OF CYTOMEGALOVIRUS LATENCY

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 该项目的目标是了解巨细胞病毒（CMV）在宿主中持续存在的细胞和分子机制。HCMV是种特异性病毒，在初次感染后在宿主中建立持续/潜伏感染。这种能力需要避免免疫检测和限制对携带病毒的细胞的致细胞病变作用。疱疹病毒通过限制大部分病毒基因组的表达来实现这一点，从而减少急性复制并最小化抗原蛋白呈递的可能性，同时保持在后期再活化的能力。疱疹病毒限制自身基因表达的过程，从而促进持续或潜伏状态，还不清楚，但可能涉及细胞和病毒因素。最近发现的RNA干扰和microRNA的广泛表达揭示了一个新的转录后基因调控层。研究表明，很大比例的转录物可以被miRNA靶向和调节，因此小RNA的调节可能代表基因表达控制中的关键机制。该项目将扩展HCMV UL 112 -1在急性和持续感染期间的表征;鉴定和表征其他病毒编码的miRNA的HCMV基因靶标;分析miRNA在急性感染期间对病毒的调控作用;并检查HCMV miRNA在单核巨噬细胞和持续感染的内皮细胞中的表达和功能。阐明miRNA调控HCMV基因表达的机制将为疱疹病毒和miRNA领域的研究做出重要贡献。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This project's goal is to develop an understanding of the cellular and molecular mechanisms of cytomegalovirus (CMV) persistence in the host. HCMV is a species-specific virus that establishes a persistent/latent infection in the host after primary infection. This ability requires avoidance of immune detection and limitation of cytopathic effect on cells harboring virus. Herpesviruses achieved this by restricting expression of the majority of the viral genome, thereby reducing acute replication and minimizing the potential for presentation of antigenic proteins, while maintaining the ability to reactivate at a later stage. The process by which herpesviruses restrict their own gene expression, thereby promoting a persistent or latent state, is not well understood, but is likely to involve both cellular and viral factors. The recent discovery of RNA interference and the widespread expression of microRNAs has uncovered a new layer of post-transcriptional gene regulation. Studies have suggested that a large percentage of transcripts may be targeted and regulated by miRNAs, thus regulation by small RNAs may represent a crucial mechanism in the control of gene expression. This project will extend the characterization of HCMV UL112-1 during acute and persistent infection; identify and characterize the HCMV gene targets of other virally encoded miRNAs; analyze the miRNAs contribution to regulation of the virus during acute infection; and examine the expression and function of the HCMV miRNAs in monocyte macrophages and persistently infected endothelial cells. Elucidating the mechanisms of miRNA regulation of HCMV gene expression will provide an important contribution to the herpesviruses and miRNA field.