PERSISTENT VIRAL INFECTION WITH LCM VIRUS

LCM 病毒持续性病毒感染

• 批准号: 3813821
• 负责人: MICHAEL B OLDSTONE
• 金额: --
• 依托单位: SCRIPPS CLINIC AND RESEARCH FOUNDATION
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3813821
• 关键词: autoimmune disorder; cell differentiation; collagen disorder; complementary DNA; electron microscopy; gene expression; genetic manipulation; genetic promoter element; genetically modified animals; human tissue; insulin; insulin dependent diabetes mellitus; laboratory mouse; laboratory rat; latent virus infection; lymphocyte; lymphocytic choriomeningitis virus; mature animal; messenger RNA; neurons; newborn animals; noncytopathogenic virus; nucleic acid hybridization; pancreatic islet function; peptide hormone biosynthesis; somatotropin; thyroglobulin; thyroid function; tissue /cell culture; virus RNA; virus diseases; virus genetics; virus protein; virus related diabetes mellitus

This subproject proposes the following studies to further delineate the role of persistent infections in luxury function alternation of differentiated cells: (1) Quantitation of the GH deficiency and reconstruction of GH-deficient mice; (2) Analysis of GH peptides to determine whether GH has been structurally altered during viral infection; (3) Analysis of LCMV replication; (4) Measurement of the production of autoantibodies to GH and other peptide hormones; (5) Evaluation of the hypoglycemia seen in LCMV-infected mice; (6) Evaluation of the presence and distribution of LCMV antigens on the neurons of the hypothalmus; and (7) Evaluation of the role of host factors in altering homeostasis in persistently infected mice. Each of these in vivo studies may be further extended to the diabetes mellitus model. In vitro studies planned include: (1) Investigation of alternations in production of GH and prolactin by GH-3 cells persistently infected with LCMV; (2) Evaluation of the tropism of virus for GH producing cells; and (3) Evaluation of the regulation of the GH gene, the state of the viral genome (in collaboration with Dr. Peter Southern). Alterations and production of insulin in cells persistently infected with LCMV and alterations in production of antibody by hybridomas persistently infected with LCMV will be undertaken.

这个分项目提议进行下列研究，以进一步界定 持续性感染的奢侈功能交替分化 细胞：（1）GH缺乏的定量和 GH缺陷小鼠;（2）分析GH肽以确定GH是否具有 在病毒感染过程中结构发生改变;（3）LCMV分析 （4）测定抗GH自身抗体的产生， 其他肽类激素;（5）评价低血糖， LCMV感染的小鼠;（6）LCMV的存在和分布的评价 下丘脑神经元上的抗原;和（7）评估 宿主因素在改变持续感染小鼠体内平衡中的作用。 这些体内研究中的每一个都可以进一步扩展到糖尿病 模型。 计划的体外研究包括：（1）研究 GH-3细胞持续分泌GH和催乳素的变化 （2）病毒对GH产生的嗜性评价 （3）评估GH基因的调节， 病毒基因组（与Peter Southern博士合作）。 持续感染的细胞中胰岛素的变化和产生 LCMV和杂交瘤持续产生抗体的改变 感染了LCMV的人将被感染。