What can characterization of cerebrospinal fluid escape populations teach us about viral reservoirs in the central nervous system?
What can characterization of cerebrospinal fluid escape populations teach us about viral reservoirs in the central nervous system?
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DOI：
10.1097/qad.0000000000002253
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发表时间：
2019-12-01
期刊：
影响因子：
3.8
通讯作者：
Price, Richard W.
中科院分区：
文献类型：
--
作者：
Joseph, Sarah B.;Trunfio, Mattia;Price, Richard W.
目的：目的：综述中枢神经系统（CNS）中病毒宿主产生CSF（脑脊液）逃逸群的证据。设计图：CSF逃逸是一种罕见的现象，其中接受抑制性ART的个体具有良好控制的全身感染，其CSF中的HIV-1 RNA水平升高。然而，CSF逃逸的罕见性加上相对较低的CSF病毒载量阻碍了对这些人群的详细分析。在这里，在以前的研究中，我们进行了遗传和表型评估的CSF逃逸人口，以确定CSF逃逸是由中枢神经系统水库或通过中枢神经系统的细胞运输。研究方法：我们报告的HIV-1病毒载量的CSF和血浆中的4个人与CSF逃逸（一个新的例子和三个以前描述的例子）。我们对病毒env基因进行了系统发育分析，以评估CSF逃逸群体内的多样性，并进行了进入分析，以确定Env蛋白是否适合进入巨噬细胞/小胶质细胞。结果：两个人的CSF逃逸产生的CNS水库。相比之下，其余两例病例可能是由于迁移到CNS并释放病毒的细胞产生的短暂病毒。结论：总之，我们的分析表明，复制能力的HIV-1可以持续在中枢神经系统在ART，但不是所有的情况下，CSF逃逸产生的中枢神经系统水库。我们的研究结果还表明，CD 4（+）T细胞和巨噬细胞/小胶质细胞可以作为持久的病毒库在中枢神经系统。
Objective: To review the evidence that CSF (cerebrospinal fluid) escape populations are produced by viral reservoirs in the central nervous system (CNS). Design: CSF escape is a rare phenomenon in which individuals on suppressive ART have well controlled systemic infections with elevated levels of HIV-1 RNA in their CSF. However, the rarity of CSF escape coupled with relatively low CSF viral loads has impeded detailed analyses of these populations. Here, and in a previous study, we performed genetic and phenotypic assessments of CSF escape populations to determine whether CSF escape is produced by CNS reservoirs or by cells trafficking through the CNS. Methods: We report HIV-1 viral loads in the CSF and blood plasma of four individuals with CSF escape (one new example and three previously described examples). We performed phylogenetic analyses of the viral env gene to evaluate diversity within the CSF escape populations and performed entry analyses to determine whether Env proteins were adapted to entering macrophage/microglia. Results: Two individuals had CSF escape produced by CNS reservoirs. In contrast, the remaining two cases were likely because of transient viral production from cells migrating into the CNS and releasing virus. Conclusion: Together our analyses indicate that replication-competent HIV-1 can persist in the CNS during ART, but that not all cases of CSF escape are produced by CNS reservoirs. Our results also suggest that both CD4(+) T cells and macrophage/microglia can serve as persistent viral reservoirs in the CNS.