当HIV侵入了你的脑子

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三十年前科学家发现了HIV。这么多年，有很多研究人员投入了大量时间，然而HIV及其引起的AIDS仍然没有特效药。HIV仍然是人类健康的头号杀手之一，是非洲人群死亡的罪魁祸首。

HIV对中枢神经系统的影响的问题早有报道。在上世纪80年代和90年代，科学家们就发现了在HIV感染者中，感染时间很长的人群中出现了运动障碍和认知障碍。然而具体的机制还不清楚。

近期在线发表在《Plos Pathogens》的文章，部分地解释了为啥HIV屡除不尽的原因。因为HIV病毒比我们想象的更加“阴险”。耶鲁大学医学院和北卡罗来纳大学的研究人员们发现，在HIV感染后的四个月内，HIV病毒就可以突破血脑屏障，进入大脑，并在大脑中稳定存在。一些时间之后，这些HIV病毒逐渐发生变异，开始变得不同于血液循环系统中的那些HIV病毒颗粒。然而，针对血液中的抗HIV药物并不能很好地杀死那些在脑部存在的变异后的HIV病毒。因而，在一定时间之后，这些存活下来的变异HIV病毒能够对神经系统和精神健康产生很大的负面影响，比如可以造成大脑的萎缩。

研究者们采集了72份美国加州旧金山的HIV新近感染者的血液和脑脊液样品。他们发现，仅仅在几个月内，70个人中的脑脊液中可以检出HIV的存在。被试验者中的四分之一的人在一年后，被发现他们体内在中枢神经系统中的HIV可以独立于血液循环系统中的HIV完成复制。

在脑部的很多外来物都是危险的。正如文章作者提到的，“我们的研究的意义在于，某些特定的脑部病毒感染，可以从血液循环进入大脑。而这些感染，往往会对人产生很多负面地认知相关的疾病。”

如今，已经有超过30种抗HIV的药物，在发达国家，20岁左右感染HIV并立即接受治疗的人可以活到55岁左右。2011年的一项研究表明，在感染HIV早期就开始接受治疗的话，在男同性恋的恋人中，HIV通过性行为传播的感染率可以下降96%。或许，HIV特效药终会出现，AIDS也终将被治愈。

然而，HIV并没有被我们很好的认知，太多的问题等着科学家去解决。我们需要希望，但是也要认清现实。抗HIV的路还很长很长。

（生物谷Bioon.com）

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Compartmentalized Replication of R5 T Cell-Tropic HIV-1 in the Central Nervous System Early in the Course of Infection

Christa Buckheit Sturdevant, Sarah B. Joseph, Gretja Schnell, Richard W. Price, Ronald Swanstrom, Serena Spudich

Abstract
Compartmentalized HIV-1 replication within the central nervous system (CNS) likely provides a foundation for neurocognitive impairment and a potentially important tissue reservoir. The timing of emergence and character of this local CNS replication has not been defined in a population of subjects. We examined the frequency of elevated cerebrospinal fluid (CSF) HIV-1 RNA concentration, the nature of CSF viral populations compared to the blood, and the presence of a cellular inflammatory response (with the potential to bring infected cells into the CNS) using paired CSF and blood samples obtained over the first two years of infection from 72 ART-naïve subjects. Using single genome amplification (SGA) and phylodynamics analysis of full-length env sequences, we compared CSF and blood viral populations in 33 of the 72 subjects. Independent HIV-1 replication in the CNS (compartmentalization) was detected in 20% of sample pairs analyzed by SGA, or 7% of all sample pairs, and was exclusively observed after four months of infection. In subjects with longitudinal sampling, 30% showed evidence of CNS viral replication or pleocytosis/inflammation in at least one time point, and in approximately 16% of subjects we observed evolving CSF/CNS compartmentalized viral replication and/or a marked CSF inflammatory response at multiple time points suggesting an ongoing or recurrent impact of the infection in the CNS. Two subjects had one of two transmitted lineages (or their recombinant) largely sequestered within the CNS shortly after transmission, indicating an additional mechanism for establishing early CNS replication. Transmitted variants were R5 T cell-tropic. Overall, examination of the relationships between CSF viral populations, blood and CSF HIV-1 RNA concentrations, and inflammatory responses suggested four distinct states of viral population dynamics, with associated mechanisms of local viral replication and the early influx of virus into the CNS. This study considerably enhances the generalizability of our results and greatly expands our knowledge of the early interactions of HIV-1 in the CNS.

Author Summary
Early HIV-1 CNS replication likely provides a foundation for brain injury and a potentially important tissue reservoir. To explore the character and timing of emergence of early HIV-1 CNS replication, we examined paired cerebrospinal fluid (CSF) and blood samples from 72 ART-naïve adults, with one-half having longitudinal samples, during the first two years following HIV-1 subtype B infection. In a cross sectional analysis over the first two years of infection, 10–25% of subjects had evidence of either local viral replication in the CNS, defined by the presence of CSF compartmentalization, or a robust inflammatory response, and in approximately 16% of subjects this CNS involvement persisted over time. In some subjects, one of two transmitted viruses replicated predominantly within the CNS, providing insight into how HIV-1 can establish independently replicating populations early in different parts of the body. Based on their entry phenotype, all viruses were selected for replication in CD4+ T cells, although this phenotype was slightly altered in the compartmentalized virus. Overall, we suggest four states to model the nature of HIV-1 CNS infection, which imply distinct mechanisms of virus/host interaction within the CNS during early infection.

http://journals.plos.org/plospat ... ournal.ppat.1004720

此情可待bm

    非常好的文章。
    在感染早起血液中已R4嗜性的病毒为主，感染后期R5病毒逐渐占优势。在脑部R5病毒在感染早起就已大量出现，说明脑部是HIV重要的病毒驻存库。  HIV的区室化（Compartmention）特性非常明显，体内的病毒存在多种突变类群。