THE ROLE OF CYTOMEGALOVIRUS PHOSPHOPROTEIN 65 IN VIRUS REPLICATON IN VIVO

巨细胞病毒磷酸蛋白65在体内病毒复制中的作用

• 批准号: 7958465
• 负责人: VICTOR Robert DEFILIPPIS
• 金额: $ 3.45万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-04 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7958465
• 关键词: Animals; Antiviral Agents; Capsid; Cellular Immunity; Chronic; Computer Retrieval of Information on Scientific Projects Database; Cytomegalovirus; Cytomegalovirus Infections; Cytomegalovirus Vaccines; Cytoplasm; Development; Funding; Grant; Growth; Immune response; In Vitro; Infection; Institution; Macaca; Macaca mulatta; Outcome; Primates; Proteins; Research; Research Personnel; Resources; Role; Source; United States National Institutes of Health; Virus; Virus Diseases; Virus Replication; cytomegalovirus matrix protein 65kDa; design; immunogenicity; in vivo; mutant; vector vaccine

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. Cytomegalovirus (CMV) protein pp65 modulates the host immune response yet simultaneously is the primary antiviral target of cellular immunity. pp65 is the most abundant component of the Rhesus CMV (RhCMV) and human CMV (HCMV) tegument, a protein-rich layer between the capsid and the envelope that is released into the cytoplasm. Interestingly, pp65 is not required for in vitro growth of either virus. This allowed us to generate a pp65-deficient RhCMV to examine whether 1) pp65's immunomodulatory functions are critical for virus survival in vivo; or 2) pp65 immunogenicity limits virus replication in healthy animals. Infection of rhesus macaques (RMs) with mutant RhCMV will allow examination of the importance of pp65 for CMV infection in vivo. We will infect CMV-na¿ve macaques with pp65-deleted RhCMV and evaluate whether this virus is able to establish primary and chronic infection and, if so, how virological and immunological parameters compare to previous observations made during infection with wild type RhCMV. Depending on the outcome, we will evaluate whether pp65-deleted virus is able to re-infect these animals. If pp65-encoded functions are required for productive infection, we expect replication of the mutant to be either undetectable or diminished. Conversely, if pp65 immunogenicity is crucial to the ability of the host immune response to control virus infection we predict that replication of the pp65-deleted virus will be greater than that for wild type. The outcome has implications both for the design of CMV vaccines and antivirals as well as the development of CMV as a vaccine vector.

该副本是使用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这是调查员的机构。 巨细胞病毒（CMV）蛋白PP65调节宿主免疫增强响应，但仅仅是细胞免疫史的主要抗病毒靶标。 PP65是恒河猴CMV（RHCMV）和人CMV（HCMV）团队中最丰富的组成部分，这是Capsid和包膜之间蛋白质富含蛋白质的层，并释放到细胞质中。有趣的是，两种病毒的体外生长都不需要PP65。这使我们能够生成PP65缺乏率RHCMV检查1）PP65的免疫调节功能是否对于体内病毒生存至关重要；或2）PP65免疫原性限制了健康动物的病毒复制。用突变rhCMV感染猕猴（RMS）将允许研究PP65在体内CMV感染的重要性。我们将用pp65删除的RHCMV感染CMV-NACHOMAQUS，并评估该病毒是否能够建立原发性和慢性感染，如果是的，则与野生型RHCMV感染期间的先前观察结果相比，病毒学和免疫学参数与先前的观察结果相比如何。根据结果​​的不同，我们将评估PP65缺失的病毒是否能够重新感染这些动物。如果产品感染需要PP65编码的功能，我们预计突变体的复制是无法检测的或减少的。相反，如果PP65免疫原性对于宿主免疫响应控制病毒感染的能力至关重要，那么我们预测PP65骨骼病毒的复制将大于野生型。结果对CMV疫苗和抗病毒药的设计以及CMV作为疫苗载体的开发都有意义。