GENETICS OFNEUROPATHOGENIC SIV INFECTION

神经病原性 SIV 感染的遗传学

• 批准号: 7562557
• 负责人: FRANCIS J NOVEMBRE
• 金额: $ 9.16万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7562557
• 关键词: Affect; Anti-Retroviral Agents; Area; Brain; Computer Retrieval of Information on Scientific Projects Database; Data; Dementia; Development; Disease; Evolution; Funding; Genotype; Grant; Institution; Knowledge; Lymphoid Tissue; Macaca; Molecular Cloning; Neurologic; Persons; Phenotype; Research; Research Personnel; Resources; Role; SIV; Source; Tissues; United States National Institutes of Health; Viral; Virus; Virus Diseases; genetic selection; lymph nodes; macrophage; nervous system disorder

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. he unusual charAIDS dementia is a progressive neurological disease that affects a significant portion of HIV-infected persons, even in the presence of anti-retroviral therapy. A major gap in knowledge concerns the evolution of virus in the CNS and the role of viral genotype in the induction of neurologic disease. We have identified a simian immunodeficiency virus (SIV) isolate, termed SIVsmmFGb that is highly neuropathogenic in infected pigtailed macaques. The central hypothesis to be evaluated is that there is separate genetic selection and evolution of SIV that occurs in the CNS, which is directly related to the development of neurologic disease. Specific hypotheses investigated are: 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 development of neurologic disease. SIV sequences derived from the SIVsmmFGb virus stock as well as from four areas of the brain and from several lymph nodes of both sets of macaques are currently being cloned and analyzed. In the V1 region of Env, we found eight (8) different groups of virus present in the uncloned SIVsmmFGb stock. When compared with sequences derived from the tissues of infected macaques, data from the first group of six macaques is suggestive of specific viral sequences responsible for initial neuroinvasion; where specific groups are present in the CNS, but not in the periphery. A unique molecular clone of SIV derived from the brain of a SIVsmmFGb-infected macaque can only infect macrophages and maintains this phenotype even in macaques infected with the virus for over two years. acteristics of the virus.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 艾滋病痴呆症是一种进行性神经系统疾病，即使在抗逆转录病毒治疗的情况下，也会影响相当一部分艾滋病毒感染者。 一个主要的知识缺口涉及病毒在中枢神经系统中的演变和病毒基因型在诱导神经系统疾病中的作用。 我们已经确定了一种猴免疫缺陷病毒（SIV）分离株，称为SIVsmmFGb，在感染的猪尾猕猴中具有高度神经致病性。 待评估的中心假设是，在CNS中发生的SIV存在单独的遗传选择和进化，这与神经系统疾病的发展直接相关。 研究的具体假设是：1）病毒进入CNS后发生基因型选择; 2）CNS与淋巴组织不同时病毒进化; 3）CNS中发生基因型区室化，并与神经系统疾病的发生相关; 4）SIV在CNS中沿着基因型进化，也发生表型进化，这促进了神经系统疾病的发生。目前正在克隆和分析来自SIVsmmFGb病毒库以及来自两组猕猴的大脑的四个区域和几个淋巴结的SIV序列。 在Env的V1区，我们发现未克隆的SIVsmmFGb原液中存在8个不同的病毒组。 当与来自感染猕猴组织的序列相比时，来自第一组6只猕猴的数据提示负责初始神经侵袭的特定病毒序列;其中特定组存在于CNS中，但不在外周中。 来源于SIVsmmFGb感染的猕猴脑的SIV的独特分子克隆仅能感染巨噬细胞，并且即使在病毒感染的猕猴中维持这种表型超过两年。病毒的特征。