PLoS ONE：HIV病毒致命进化模式
美国科学家近日通过研究，揭示了HIV病毒在人的一生中发展成致命艾滋病（AIDS）病毒的过程。这一发现将有助于开发针对早期HIV病毒的药靶。相关论文9月份发表在《公共科学图书馆.综合》（PLoS ONE）上。
此次研究由美国佛罗里达大学医学院的Marco Salemi领导完成。他表示，之前人们所知道的仅仅是HIV会发生变异，而一旦变异发生，人体就开始发展AIDS。但人们对其中的机制却所知甚少。
在最新的研究中，研究人员提取了四个天生带有HIV病毒儿童的血液和组织样本，这些样本的提取时间分别在刚出生时、贯穿生命期间以及刚死亡后不久。应用一种高分辨计算技术，研究人员监控了一种帮助HIV感染人类细胞的蛋白的变异情况，并将病毒分成了两个族群，R5和X4。R5通常在感染的早期阶段大量出现，而X4则在AIDS即将真正形成之前开始出现。此次实验的目的即是要找出X4最初出现的时间和地点。
结果发现，X4病毒主要分布在胸腺里。这表明这些病毒是在胸腺里进行进化，或者至少是在这里进行停留和复制。研究人员同时揭示出，X4病毒并不是一直存在于身体里，而是在AIDS开始发作前由R5直接进化而来。此外，研究人员还发现，虽然各个儿童的病史存在差异，但是HIV在每个儿童体内的进化路径却很相似。
Goodenow认为，这表明HIV病毒的进化路径可能并不是完全随机的，它可能遵循一种设计好的发展程序。
英国牛津大学动物学系的Oliver Pybus表示，这是一项卓越的研究，它表明了感染过程中HIV精密的进化和改编模式，并且第一次揭示了机体免疫细胞的运作与病毒进化之间的联系。
Goodenow表示，下一步的研究将是追踪成人体内HIV病毒在治疗前后的变化情况。他同时希望此次发现能够有助于开发出一种新的药物，以干扰HIV在胸腺里的进化。（科学网 梅进/编译）
原始出处:
Phylodynamics of HIV-1 in Lymphoid and Non-Lymphoid Tissues Reveals a Central Role for the Thymus in Emergence of CXCR4-Using Quasispecies
1 Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, Florida, United States of America, 2 Department of Anthropology, University of Florida, Gainesville, Florida, United States of America, 3 Department of Pediatrics, Division of Immunology, Rheumatology, and Infectious Diseases, University of Florida, Gainesville, Florida, United States of America, 4 Department of Pediatrics, Division of Allergy, Immunology, and Rheumatology, University of South Florida and All Children's Hospital, St. Petersburg, Florida, United States of America
Abstract
Background
During HIV-1 infection coreceptor switch from CCR5- (R5)- to CXCR4 (X4)-using viruses is associated with disease progression. X4 strains of HIV-1 are highly cytopathic to immature thymocytes. Virtually no studies have evaluated the HIV-1 quasispecies present in vivo within thymic and lymphoid tissues or the evolutionary relationship between R5 and X4 viruses in tissues and peripheral blood.
Methodology/Principal Findings
High-resolution phylodynamic analysis was applied to virus envelope quasispecies in longitudinal peripheral blood mononuclear cells (PBMCs) and lymphoid and non-lymphoid tissues collected post mortem from therapy naïve children with AIDS. There were three major findings. First, continued evolution of R5 viruses in PBMCs, spleen and lymph nodes involved multiple bottlenecks, independent of coreceptor switch, resulting in fitter quasispecies driven by positive selection. Second, evolution of X4 strains appeared to be a sequential process requiring the initial fixation of positively selected mutations in V1-V2 and C2 domains of R5 variants before the emergence of high charge V3 X4 variants. Third, R5 viruses persisted after the emergence of CXCR4-using strains, which were found predominantly but not exclusively in the thymus.
Conclusions/Significance
Our data indicate that the evolution of X4 strains is a multi-step, temporally structured process and that the thymus may play an important role in the evolution/amplification of coreceptor variants. Development of new therapeutic protocols targeting virus in the thymus could be important to control HIV-1 infection prior to advanced disease.
Received: April 6, 2007; Accepted: September 6, 2007; Published: September 26, 2007
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