MOLECULAR MECHANISMS OF HIV POST-INTEGRATION LATENCY

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 尽管在许多接受高效抗逆转录病毒治疗的HIV感染患者中几乎完全抑制了可检测到的病毒，但在治疗中断后病毒血症迅速复发。 整合后潜伏期是指潜伏感染的静息记忆CD 4 + T细胞含有转录沉默整合的HIV-1基因组。 整合后潜伏期有助于HAART下病毒的持续存在，并代表了根除HIV感染的已知障碍。 为了研究艾滋病治疗的新方法，我们的非人灵长类动物模型使用RT-SHIV，一种含有HIV-1逆转录酶（RT）的猿免疫缺陷病毒嵌合体。 建立了RT-SHIV感染猕猴组织中病毒DNA（vDNA）和病毒RNA（vRNA）的提取、预扩增和实时荧光PCR分析方法。 这些方法用于鉴定用由依法韦仑、恩曲他滨和替诺福韦组成的有效HAART方案治疗的RT-SHIV感染的猕猴中的病毒储库。在HAART期间，在许多解剖位置的组织中检测到病毒RNA和DNA。 HAART处理的猕猴中最高水平的vDNA和vRNA存在于淋巴组织中，特别是脾、淋巴结和胃肠道组织。 这项研究是第一次对HAART期间灵长类艾滋病病毒的组织和器官分布进行全面分析。 这些数据表明HAART期间组织中残留病毒的广泛持久性。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Despite the near complete suppression of detectable virus in many HIV infected patients undergoing highly active antiretroviral therapy, viremia reemerges rapidly after interruption of treatment. Postintegration latency refers to latently infected resting memory CD4+ T cells containing transcriptionally silent integrated HIV-1 genomes. Postintegration latency contributes to the persistence of the virus under HAART and represents a known barrier to eradication of HIV infection. To investigate novel approaches for AIDS therapy, our nonhuman primate model uses RT-SHIV, a chimera of simian immunodeficiency virus containing the HIV-1 reverse transcriptase (RT). Methods were developed for extraction, pre-amplification and real-time PCR analyses of viral DNA (vDNA) and viral RNA (vRNA) in tissues from RT-SHIV-infected macaques. These methods were used to identify viral reservoirs in RT-SHIV-infected macaques treated with a potent HAART regimen consisting of efavirenz, emtricitabine and tenofovir. Viral RNA and DNA were detected during HAART in tissues from numerous anatomical locations. The highest levels of vDNA and vRNA in HAART-treated macaques were in lymphoid tissues, particularly spleen, lymph nodes, and gastrointestinal tract tissues. This study is the first comprehensive analysis of tissue and organ distribution of a primate AIDS virus during HAART. These data demonstrate widespread persistence of residual virus in tissues during HAART.