Murine Model of Gammaherpesvirus Latency

伽马疱疹病毒潜伏期小鼠模型

• 批准号: 6633947
• 负责人: JEFFERY T SAMPLE
• 金额: $ 25.81万
• 依托单位: ST. JUDE CHILDREN'S RESEARCH HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-01 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6633947
• 关键词: B lymphocyte; Burkitt's lymphoma; Epstein Barr virus; Kaposi's sarcoma; dendritic cells; disease /disorder model; gene induction /repression; host organism interaction; human herpesvirus 8; laboratory mouse; latent virus infection; macrophage; microorganism immunology; polymerase chain reaction; recombinant virus; southern blotting; virus genetics

DESCRIPTION (provided by applicant): The long-term objective of the proposed research is to define the mechanisms that enable the gamma herpesviruses to persist indefinitely within their immunocompetent hosts. These mechanisms underlie the pathogenesis and oncogenic potential associated with these viruses, particularly in individuals with acquired or inherited immunodeficiencies. Unfortunately, due to the extreme host restrictions of the human gamma-herpesviruses Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV), it has not been possible to directly address the mechanisms responsible for EBV and KSHV persistence in a relevant host setting. Infection of laboratory mice with the murine gamma-herpesvirus MHV-68 (closely related to KSHV) offers a highly tractable and potential model of human gamma-herpesvirus persistence, but viral latency in this system has not been sufficiently characterized at the molecular level to enable exploitation of this model for these purposes. Therefore, the immediate goals of the proposed research are to define the molecular characteristics of MHV-68 latency. To obtain our objective, we propose three specific aims. Under Aim 1 we will define the programs of MHV-68 latency gene expression during the establishment and maintenance phases of latency within the hematopoietic-cell reservoirs of latent virus (activated and resting B cells, macrophages, and dendritic cells). Specifically, we will screen these cells by RT-PCR and Southern blot hybridization for expression of the MHV-68 latency genes M2, M3, M1 1, 72, 73 and 74. Additionally, we propose to identify potentially novel MHV-68 latency genes expressed in these cells that are not apparent from analysis of the viral genornic DNA sequence. Under Aim 2 we will address the functions of three latency-associated genes: M2, 73 and 74, for which little or no information is available. Under Aim 3 we will define the impact of MHV-68 latency on cellular gene expression in vivo at the cellular level. Together, these specific aims will fill the significant gaps that currently remain in our knowledge of the latent life cycle of MHV-68, as well as provide better insight into the mechanisms that the gamma-herpesviruses as a group exploit to maintain latency, and thus contribute to their pathogenic potential.

描述（由申请人提供）：建议的长期目标