近日，佛罗里达大学科研人员发现了艾滋病（HIV）病毒在人体内的进化历程，此项发现为确定早期HIV病毒形式，研究新型治疗措施，开发新型治疗药物找到了新方向。该项科研成果发表在美国《公共科学图书馆·综合》（PLoS ONE）期刊上。
研究人员跟踪观察了4个出生时感染HIV的儿童。他们一出生就被采了血液样本，并对患者进行终生跟踪研究。被研究的HIV病毒分为CCR5（R5）和CXCR4（X4）两种。研究人员发现，在早期感染阶段，R5病毒数量较多，而X4病毒的出现则标志着HIV感染已经进入了晚期。
佛罗里达医学院病理免疫与试验医学助理教授马可·塞尔米说，此前我们只知道，HIV病毒一旦变异，就会很快发展成艾滋病。但从开始感染到死亡整个过程中，病毒是如何变异的，变异发生在什么部位，还没有人知道。
通过观察，研究人员发现胸腺是病毒定居和复制的场所，胸腺位于胸骨后面，也是T细胞分化与成熟的场所，具有免疫调节功能，大部分的病毒变异发生在胸腺，到了感染晚期，病毒X4已经控制了胸腺。
研究人员还发现，X4病毒并非一直存在于人体中，而是在艾滋病发作之前由R5病毒直接进化而来，X4病毒比R5病毒的致病性更强。但事实上，病人致死是由于R5病毒所造成的，但X4病毒的某些进化机理真正起到了促进作用。如果我们能了解这种机制或者干扰病毒发展到胸腺的能力，就可以为相关治疗药物的研发找到一条新路。
牛津大学动物系研究人员奥立佛·派巴斯表示，这项研究准确地揭示了感染过程中HIV病毒的进化和生长变异以及身体免疫细胞在病毒进化过程中的行为，这可以作为临床感染结果的测定手段。(科技日报)
原始出处:
Received: April 6, 2007; Accepted: September 6, 2007; Published: September 26, 2007
Phylodynamics of HIV-1 in Lymphoid and Non-Lymphoid Tissues Reveals a Central Role for the Thymus in Emergence of CXCR4-Using Quasispecies
Marco Salemi1*#, Brant R. Burkhardt1¤#, Rebecca R. Gray1,2, Guity Ghaffari1,3, John W. Sleasman4, Maureen M. Goodenow1,3*
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.
全文链接：http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0000950
