Analysis of HIV-1 in mucosal tissue in elite suppressors

描述（由申请人提供）：精英抑制者是HIV-1感染者，在未接受抗逆转录病毒治疗的情况下，病毒载量维持在<50拷贝/ml。尽管这种病毒复制的良好控制，这些患者继续具有残留的病毒血症，如通过含有复制能力HIV-1的潜伏感染的CD 4 + T细胞的存在所确定的。 有趣的是，外周血中这些潜伏感染细胞的频率在ES中比在具有不可检测的病毒载量的抑制性HAART方案的患者中低得多。这可能表明，ES可能是根除这些细胞的最佳候选策略。只有当ES中这些细胞的总负荷低得多时，这才是正确的。因此，我们建议在两个不同的粘膜网站在ES。研究表明，在HAART患者中，肠道相关淋巴组织（GALT）中潜伏感染的CD 4 T细胞的频率比外周CD 4 + T细胞的频率高10倍。我们想确定这种关系在ES中是否成立。我们还将研究这些患者肺部潜伏感染的CD 4 + T细胞的频率，以便更好地近似ES中感染细胞的总负荷。 我们最近还提供了证据，表明ES患者血浆中存在非常低水平的HIV-1正在进行HIV-1复制和进化。从外周CD 4 + T细胞获得的病毒几乎没有进化，这意味着其他一些隔室中的CD 4 + T细胞是导致血浆变体的持续复制和进化的来源。通过分析从每个区室获得的序列，我们将能够确定患者中正在进行的复制的来源。 这项工作将是重要的，因为它可能表明，ES是研究的最佳候选者，可能通过根除潜伏感染的CD 4 + T细胞来治愈HIV-1感染。

DESCRIPTION (provided by applicant): Elite suppressors are HIV-1 infected patients who maintain viral loads of <50 copies/ml without antiretroviral therapy. Despite this excellent control of viral replication, these patients continue to have residual viremia as determined by the presence of latently infected CD4+ T cells that contain replication-competent HIV-1. Interestingly, the frequency of these latently infected cells in peripheral blood is much lower in ES than in patients on suppressive HAART regimens with undetectable viral loads. This might suggest that ES may be the best candidates for strategies that could lead to eradication of these cells. This would only hold true if the total burden of these cells was much lower in ES. We therefore propose to look at two different mucosal sites in ES. Studies have suggested that the frequency of latently infected CD4 T cells in the gut associated lymphoid tissue (GALT) is ten times higher than the frequency in peripheral CD4+ T cells in patients on HAART. We want to determine whether this relationship holds true in ES. We will also look at the frequency of latently infected CD4+ T cells in the lungs of these patients so as to have a better approximation of the total burden of infected cells in ES. We have also recently provided evidence of ongoing HIV-1 replication and evolution of the very low level of HIV-1 present in the plasma of ES. There was very little evolution of the virus obtained from peripheral CD4+ T cells implying that CD4+ T cells in some other compartment are the source of the ongoing replication and evolution that lead to the plasma variants. By analyzing the sequence obtained from each compartment we would be able to determine the source of ongoing replication in the patients. This work will be important because it may suggest that ES are the best candidates for studies that could potentially cure HIV-1 infection by the eradication of latently infected CD4+ T cells.