GENETICS OFNEUROPATHOGENIC SIV INFECTION

神经病原性 SIV 感染的遗传学

• 批准号: 7715711
• 负责人: FRANCIS J NOVEMBRE
• 金额: $ 9.52万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7715711
• 关键词: AIDS Dementia Complex; Address; Affect; Animals; Brain; Cercocebus atys; Computer Retrieval of Information on Scientific Projects Database; Data; Development; Disease; Evolution; Funding; Genotype; Grant; Growth; Infection; Institution; Knowledge; Lymphoid; Lymphoid Tissue; Macaca; Molecular Cloning; Mutation; Neurologic; Persons; Research; Research Personnel; Resources; Role; SIV; Source; System; Time; United States National Institutes of Health; Viral; Virus; Virus Diseases; day; genetic selection; macrophage; nervous system disorder; virus characteristic

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. AIDS dementia is a progressive neurological disease that affects a significant portion of HIV-infected persons. A major gap in knowledge concerns the role of viral sequences in the induction of neurologic disease. We have identified a simian immunodeficiency virus (SIV) isolate, termed SIVsmmFGb, derived from a sooty mangabey, which is highly neuropathogenic in pigtailed macaques. The central hypothesis is that there is genetic selection and evolution of SIV that occurs in the CNS, separate from that in the lymphoid system, which is directly related to the development of neurologic disease. Specifically, 1) genotypic selection occurs after virus enters the CNS; 2) viral evolution is the CNS is distinct from the lymphoid tissue; 3) genotypic compartmentalization occurs in the CNS and is related to the development of neurologic disease; and 4) along with genotypic evolution of SIV in the CNS, phenotypic evolution also occurs, which facilitates growth in the CNS and also facilitates development of neurologic disease. To address these hypotheses, we compared the selection and evolution of SIV genotypes in the CNS and the lymphoid system at immediate early (7 days) and early times (2 months) after infection. Current data suggests that while the initial invasion of the CNS by virus is not limited to specific sequences, there is an initial compartmentalization of sequences within the CNS and the lymphoid system. We have shown that a unique molecular clone of SIV derived from the brain of a SIVsmmFGb-infected macaque can only infect macrophages. This virus has been inoculated into two pigtailed macaques to investigate the effects of such an unusual virus. To date, the animals have shown no signs of disease development and have not corrected the mutation responsible for the unusual characteristics of the virus.

该副本是利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，这不一定是调查员的机构。 艾滋病痴呆症是一种渐进的神经系统疾病，会影响受HIV感染者的很大一部分。 知识的主要差距涉及病毒序列在诱导神经系统疾病中的作用。我们已经确定了源自烟熏芒果的SIVSMMFGB，称为SIVSMMFGB，它鉴定出一种猿猴免疫缺陷病毒（SIV）分离株，该病毒在柔软的猕猴中具有高度神经性发病。 中心假设是，在中枢神经系统中存在遗传选择和SIV的进化，与淋巴系统中的遗传选择和与神经系统疾病的发展直接相关的SIV。 具体而言，1）基因型选择是在病毒进入中枢神经系统之后发生的； 2）病毒进化是中枢神经系统与淋巴组织不同。 3）基因型隔室化发生在中枢神经系统中，与神经系统疾病的发展有关； 4）随着中枢神经系统中SIV的基因型进化，还会发生表型进化，这促进了中枢神经系统的生长，并促进了神经系统疾病的发展。 为了解决这些假设，我们比较了感染后立即（7天）和早期（2个月）的CNS和淋巴系统中SIV基因型的选择和演变。 当前数据表明，尽管病毒对CNS的初始侵袭不限于特定序列，但在中枢神经系统和淋巴机系统内有初始的序列化。 我们已经表明，源自SIVSMMFGB感染的猕猴的SIV的独特分子克隆只能​​感染巨噬细胞。 该病毒已被接种到两个辫子的猕猴中，以研究这种异常病毒的作用。 迄今为止，这些动物还没有显示出疾病发展的迹象，也没有纠正导致病毒异常特征的突变。