GENETICS OFNEUROPATHOGENIC SIV INFECTION

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 艾滋病痴呆症是一种进行性神经系统疾病，即使在接受抗逆转录病毒治疗的情况下，也会影响到相当一部分艾滋病毒感染者。知识上的一个主要差距涉及中枢神经系统中病毒的进化以及病毒基因型在诱发神经系统疾病中的作用。我们已经鉴定出一种猴免疫缺陷病毒(SIV)分离株，命名为SIVsmmFGb，它在感染的猪尾猕猴中具有高度的神经致病性。需要评估的中心假设是，在中枢神经系统中存在SIV的单独基因选择和进化，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后发生基因选择；2)病毒进化是CNS与淋巴组织不同；3)CNS发生基因区隔，与神经系统疾病的发生有关；4)随着CNS中SIV的基因进化，也发生表型进化，促进神经系统疾病的发展。来自SIVsmmFGb病毒种群以及来自两组猕猴大脑四个区域和几个淋巴结的SIV序列目前正在被克隆和分析。在Env的V1区域，我们发现在未克隆的SIVsmmFGb库中存在八(8)组不同的病毒。与来自受感染猕猴组织的序列相比，来自第一组六只猕猴的数据暗示了导致最初神经入侵的特定病毒序列；其中特定组存在于中枢神经系统，但不存在于外围。从SIVsmmFGb感染的猕猴脑中提取的SIV独特的分子克隆只能感染巨噬细胞，并在感染该病毒两年以上的猕猴中保持这种表型。病毒的特征。

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.