MURINE MODEL FOR MONKEY B VIRUS INFECTION

猴 B 病毒感染的鼠模型

• 批准号: 6604145
• 负责人: Jerry W Ritchey
• 金额: $ 22.77万
• 依托单位: OKLAHOMA STATE UNIVERSITY STILLWATER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6604145
• 关键词: Cercopithecid herpesvirus 1; Macaca; RNase protection assay; cellular immunity; central nervous system; cytokine; disease /disorder model; enzyme linked immunosorbent assay; gene expression; genotype; histopathology; humoral immunity; immune tolerance /unresponsiveness; immunocytochemistry; immunofluorescence technique; interferon gamma; laboratory mouse; laboratory rabbit; model design /development; nervous system infection; occupational hazard; pathologic process; virus cytopathogenic effect; virus genetics; virus infection mechanism; virus replication; western blottings

DESCRIPTION (provided by applicant): Nonhuman primates (NHPs) are an integral part of biomedical research programs, particularly as animal models of human disease. As long as monkeys are used for research, zoonotic infection by simian viruses will continue to be an occupational hazard. Human infections by BV, a herpes virus of macaques, commonly involve the central nervous system (CNS) and if left untreated, are usually fatal. Even though the first BV case was reported in 1934, there still remain many unanswered questions about BV. A well-characterized small animal model system that could be used to answer such questions does not exist. The goal of this project is to establish and characterize a murine model for BV infection. To achieve this goal, the ID50, CNSD50, and LD50 will be determined for BV infection in the mouse. Histopathology, immunohistochemistry, and immunofluorescence will document the anatomical and temporal spread of virus and viral lesions in the CNS and other tissues. Lesion development and viral localization will also be compared with the temporal development of humoral immunity (ELISA, Western blot), cellular immunity (antigen specific induction of IFN-gamma), and cytokine gene expression (RNAse protection assay) in both the peripheral and the CNS. Following characterization of the murine model, the model will be used to answer the question of whether BV strains isolated from rhesus macaques have greater neuroinvasive and/or neuropathogenicity potential than BV genotypes isolated from other macaque species. Establishment of a well characterized murine model system for BV infection will serve as an important resource in which hypothesis-driven studies can be performed such as evaluation of anti-viral drugs, challenge assessment of potential vaccines, and investigation of the role of various viral genes/proteins in determining the pathogenic properties of these viruses.

描述（由申请人提供）：非人灵长类动物（NHP）是生物医学研究计划的组成部分，特别是作为人类疾病的动物模型。 只要猴子被用于研究，猿类病毒引起的人畜共患病感染将继续是一种职业危害。 人类感染BV（猕猴疱疹病毒）通常涉及中枢神经系统（CNS），如果不治疗，通常是致命的。 尽管1934年报道了第一例BV病例，但关于BV仍有许多未解之谜。 目前还不存在可用于回答此类问题的特征良好的小动物模型系统。 本项目的目标是建立和表征BV感染的小鼠模型。 为了实现这一目标，将测定小鼠中BV感染的ID 50、CNSD 50和LD 50。 组织学、免疫组化和免疫荧光将记录病毒和病毒病变在CNS和其他组织中的解剖学和时间传播。 还将病变发展和病毒定位与外周和CNS中的体液免疫（ELISA、Western印迹）、细胞免疫（IFN-γ的抗原特异性诱导）和细胞因子基因表达（RNA酶保护试验）的时间发展进行比较。 在对鼠模型进行表征后，该模型将用于回答从恒河猴中分离的BV菌株是否比从其他猕猴种属中分离的BV基因型具有更大的神经侵袭性和/或神经致病性潜力的问题。 建立一个良好表征的BV感染小鼠模型系统将作为一个重要的资源，其中可以进行假设驱动的研究，如抗病毒药物的评价，潜在疫苗的挑战评估，以及各种病毒基因/蛋白在确定这些病毒的致病特性中的作用的调查。