Viral Sanctuaries during Highly Active Antiretroviral Therapy in a Nonhuman Primate Model for AIDS
Viral Sanctuaries during Highly Active Antiretroviral Therapy in a Nonhuman Primate Model for AIDS
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DOI：
10.1128/jvi.02356-09
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发表时间：
2010-03-01
影响因子：
5.4
通讯作者：
Luciw, Paul A.
中科院分区：
文献类型：
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作者：
North, Thomas W.;Higgins, Joanne;Luciw, Paul A.
高效抗逆转录病毒疗法（HAART）能够长期抑制感染者的血浆HIV-1载量，但低水平病毒持续存在，并在治疗停止后反弹。在HAART期间，这种病毒存在于潜伏感染的细胞中，例如静息的CD 4（+）T细胞，以及可能支持残留病毒复制的其他细胞类型。治疗性根除需要从所有宿主中消除病毒。我们在这里报告了一个全面的分析，这些水库的液体，细胞和组织中的恒河猴模型，模仿HAART在HIV感染的人。这种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。方法开发的提取，预扩增，和实时PCR分析的病毒DNA（vDNA）和病毒RNA（vRNA）的组织从RT-SHIV感染的猕猴。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。尸检时的血浆病毒载量范围为11至28个vRNA拷贝/ml。在HAART期间，在许多解剖位置的组织中检测到病毒RNA和DNA。其他分析提供了HAART抑制病毒的动物组织中全长病毒RNA的证据。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。
Highly active antiretroviral therapy (HAART) enables long-term suppression of plasma HIV-1 loads in infected persons, but low-level virus persists and rebounds following cessation of therapy. During HAART, this virus resides in latently infected cells, such as resting CD4(+) T cells, and in other cell types that may support residual virus replication. Therapeutic eradication will require elimination of virus from all reservoirs. We report here a comprehensive analysis of these reservoirs in fluids, cells, and tissues in a rhesus macaque model that mimics HAART in HIV-infected humans. This nonhuman primate model uses RT-SHIV, a chimera of simian immunodeficiency virus containing the HIV-1 reverse transcriptase (RT). Methods were developed for extraction, preamplification, 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. Plasma virus loads at necropsy ranged from 11 to 28 copies of vRNA per ml. Viral RNA and DNA were detected during HAART, in tissues from numerous anatomical locations. Additional analysis provided evidence for full-length viral RNA in tissues of animals with virus suppressed by HAART. The highest levels of vDNA and vRNA in HAART-treated macaques were in lymphoid tissues, particularly the spleen, lymph nodes, and gastrointestinal tract tissues. This study is the first comprehensive analysis of the tissue and organ distribution of a primate AIDS virus during HAART. These data demonstrate widespread persistence of residual virus in tissues during HAART.