Tissue and Cell Reservoirs for HIV

治疗艾滋病毒/艾滋病的成功关键取决于对奥秘的透彻和准确的理解 感染-在哪里以及如何保持艾滋病毒的持久性。这项建议的重点是巨噬细胞和 滤泡树突状细胞(FDC)作为HIV的细胞储存库，骨髓和脑作为组织储存库。 尽管它们受到的关注相对较少，但这些细胞和组织隔间很可能 代表着具有相当重要意义的艾滋病毒蓄水池。重要的是，每一个似乎都能够充当 潜在艾滋病毒感染的避难所。我们建议在这里确定这些细胞和组织是否确实可以 因为潜伏感染的宿主能够产生能够在体内播种的感染性颗粒。我们试图找出 淋巴组织和中枢神经系统之间的艾滋病毒传播模式，并确定是否 大脑可能会在外围重新播种艾滋病毒。我们还试图确定抗逆转录病毒的细胞和组织储存库。 对药物敏感的艾滋病毒与抗药性的艾滋病毒。在这些研究中，艾滋病毒基因分型将使用 同期采集的死前骨髓和颈淋巴清扫活检 标本，连同患者匹配的血浆、脑脊液(CSF)和分离的血液 同时采集单核细胞和T淋巴细胞样本，以及在活检之前和之后。 将检查HIV基因组的两个区域，包膜基因的V1-V4区域和一个1.2kb 包括蛋白酶基因和逆转录酶基因的编码部分的片段 对于大多数抗逆转录病毒耐药突变具有重要意义。以最佳方式解决……问题 大脑是否可以在外围植入艾滋病毒，我们将不仅评估存在于大脑中的艾滋病毒物种 淋巴结(LN)中的CD4+T细胞群，也与LN生发中心滤泡相关 树突状细胞(FDC)。这些调查将与对身体组织的研究相辅相成。在……里面 此外，我们试图确定骨髓中与全身性病毒学衰竭相关的事件。注意力将会 关注骨髓中HIV的表达和单核/巨噬细胞的激活。免疫组织化学与Flow 将使用细胞学方法。这些研究将产生关于艾滋病毒宿主的重要新信息， 以及骨髓中的事件对艾滋病毒免疫发病机制和疾病进展的贡献。

Success in treating HIV/AIDS is critically dependent upon a thorough and accurate understanding of occult infection---where and how HIV persistence is maintained. This proposal focuses on the macrophage and follicular dendritic cell (FDC) as cellular reservoirs for HIV, and bone marrow and brain as tissue reservoirs. Although they have received comparatively little attention, these cell and tissue compartments most probably represent HIV reservoirs of considerable significance. Importantly, each appears capable of serving as a sanctuary for latent HIV infection. We propose here to determine if, indeed, these cells and tissues can serve as latently-infected hosts able to yield infectious particles that can seed the body. We seek to identify patterns of HIV trafficking between lymphoid tissues and the Central Nervous System, and determine if the brain can reseed the periphery with HIV. We also seek to identify cell and tissue reservoirs for antiretroviral drug-sensitive, versus drug-resistant, HIV. For these studies, HIV genotyping will be performed using contemporaneously-collected ante-mortem bone marrow and excisional cervical lymph node biopsy specimens, in conjunction with patient-matched plasma, cerebrospinal fluid (CSF), and separated blood monocyte and T-lymphocyte specimens collected concomitantly, as well as prior to, and following biopsy. Two regions of the HIV genome will be examined, the V1-V4 region of the envelope gene, and a 1.2kb fragment which includes the protease gene and that portion of the reverse transcriptase gene which codes for most of the antiretroviral resistance mutations of significance. To optimally address the question of whether the brain can seed the periphery with HIV, we will evaluate the HIV species present not only within the lymph node (LN) CD4+ T-cell population, but also those associated with LN germinal center follicular dendritic cells (FDC). These investigations will be complemented with studies of post-mortem tissues. In addition, we seek to identify events in bone marrow associated with systemic virologic failure. Attention will be paid to HIV expression and monocyte/macrophage activation in marrow. Immunohistochemistry and flow cytometry methods will be used. These studies will yield important new information regarding HIV reservoirs, as well as the contributions of events in bone marrow to HIV immunopathogenesis and disease progression.