Viral Genes Essential for MHV-68 Persistent Infection in the Spleen

MHV-68 脾脏持续感染所必需的病毒基因

• 批准号: 7380067
• 负责人: REN SUN
• 金额: $ 17.21万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-12-02 至 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7380067
• 关键词: Animal Model; Applications Grants; Bacterial Artificial Chromosomes; Benign; Biological; Biological Models; Cells; Cultured Cells; Disease; Essential Genes; Fibroblasts; Genes; Genome; Goals; Herpesviridae; Human; Human Herpesvirus 4; Human Herpesvirus 8; Human Virus; Image; Imaging technology; Immune response; Immune system; In Vitro; Inbred Mouse; Individual; Infection; Knowledge; Libraries; Life; Life Cycle Stages; Lung; Lymphocyte; Lytic Phase; Malignant Neoplasms; Measures; Monitor; Murine herpesvirus 68; Mus; Mutagenesis; Nonsense Mutation; Open Reading Frames; Pathogenesis; Polymerase Chain Reaction; Preparation; Property; Research; Role; Screening Result; Screening procedure; Simplexvirus; Spleen; System; Therapeutic; Time; Vaccines; Viral; Viral Genes; Viral Genome; Viral Physiology; Virus; Virus Diseases; Virus Replication; carcinogenesis; follow-up; gene function; genetic analysis; genetic manipulation; in vivo; latent infection; member; molecular imaging; mutant; novel therapeutics; recombinant virus; research study; therapeutic target; tumor; vector; virus host interaction

DESCRIPTION: Viral genes essential for MHV-68 Persistent Infection in the Spleen Members of the gammaherpesvirus subfamily are distinct in their ability to establish latent infections in the lymphocytes and cause benign or malignant tumors in infected hosts. There are two human viruses in this subfamily, Epstein-Barr virus (EBV) and human herpesvirus-8/Kaposi's sarcoma-associated herpesvirus (HHV-8/KSHV). Murine gammaherpesvirus-68 (MHV-68) is another member of the same subfamily. Since EBV and KSHV cannot effectively replicate in cell cultures or small model animals, MHV-68 serves as an excellent model system for studying the role of both the virus and the host in viral replication and pathogenesis. The function of viral genes can be determined in the MHV-68 system, which should provide instrumental information for the related genes in human gammaherpesviruses. The long-term goal of our discovery-oriented approach is to determine the function of each viral gene by mutagenesis of the whole viral genome. MHV-68 genome is mutagenized by random insertion of signature- tagged transposons into an MHV-68 bacterial artificial chromosome. The viral genes essential for viral replication in cell cultures have been identified. The objective of this exploratory R21 application is to identify viral genes essential for establishment of long-term persistent infection in the spleen. This study will be the first comprehensive analysis of viral gene function. The results will allow us to follow up on specific viral genes with hypothesis driven study. This will open a new window for us to look into the mechanism of viral persistence, which provides possibilities of identifying potential new therapeutic targets. Furthermore define the viral genes essential for persistent infection will allow us to construct recombinant viruses that are replication competent but cannot establish persistent infection. These viruses will strongly stimulate immune responses but will not establish persistent infection to cause diseases, thus a potential vaccine strategy.

描述：MHV-68 脾脏持续感染所必需的病毒基因 伽玛疱疹病毒亚科的成员在淋巴细胞中建立潜伏感染并在受感染宿主中引起良性或恶性肿瘤的能力各不相同。该亚科中有两种人类病毒，即 Epstein-Barr 病毒 (EBV) 和人类疱疹病毒 8/卡波西肉瘤相关疱疹病毒 (HHV-8/KSHV)。鼠伽马疱疹病毒 68 (MHV-68) 是同一亚科的另一个成员。由于 EBV 和 KSHV 无法在细胞培养物或小型模型动物中有效复制，因此 MHV-68 可以作为研究病毒和宿主在病毒复制和发病机制中的作用的优秀模型系统。 MHV-68系统可以确定病毒基因的功能，这将为人类伽马疱疹病毒的相关基因提供工具信息。我们以发现为导向的方法的长期目标是通过整个病毒基因组的诱变来确定每个病毒基因的功能。通过将标记转座子随机插入 MHV-68 细菌人工染色体中，对 MHV-68 基因组进行诱变。细胞培养物中病毒复制所必需的病毒基因已被鉴定。这一探索性 R21 应用的目的是确定在脾脏中建立长期持续感染所必需的病毒基因。这项研究将是首次对病毒基因功能进行全面分析。结果将使我们能够通过假设驱动的研究来追踪特定的病毒基因。这将为我们研究病毒持久性机制打开一扇新窗口，从而为识别潜在的新治疗靶点提供可能性。此外，定义持续感染所必需的病毒基因将使我们能够构建具有复制能力但不能建立持续感染的重组病毒。这些病毒将强烈刺激免疫反应，但不会建立持续感染而导致疾病，因此是一种潜在的疫苗策略。