美國(guó)科學(xué)家近日通過研究,，揭示了HIV病毒在人的一生中發(fā)展成致命艾滋?。ˋIDS）病毒的過程。這一發(fā)現(xiàn)將有助于開發(fā)針對(duì)早期HIV病毒的藥靶,。相關(guān)論文9月份發(fā)表在《公共科學(xué)圖書館.綜合》（PLoS ONE）上,。
此次研究由美國(guó)佛羅里達(dá)大學(xué)醫(yī)學(xué)院的Marco Salemi領(lǐng)導(dǎo)完成。他表示,，之前人們所知道的僅僅是HIV會(huì)發(fā)生變異,，而一旦變異發(fā)生，人體就開始發(fā)展AIDS。但人們對(duì)其中的機(jī)制卻所知甚少,。
在最新的研究中,，研究人員提取了四個(gè)天生帶有HIV病毒兒童的血液和組織樣本，這些樣本的提取時(shí)間分別在剛出生時(shí),、貫穿生命期間以及剛死亡后不久,。應(yīng)用一種高分辨計(jì)算技術(shù)，研究人員監(jiān)控了一種幫助HIV感染人類細(xì)胞的蛋白的變異情況,，并將病毒分成了兩個(gè)族群,，R5和X4。R5通常在感染的早期階段大量出現(xiàn),，而X4則在AIDS即將真正形成之前開始出現(xiàn),。此次實(shí)驗(yàn)的目的即是要找出X4最初出現(xiàn)的時(shí)間和地點(diǎn)。
結(jié)果發(fā)現(xiàn),，X4病毒主要分布在胸腺里,。這表明這些病毒是在胸腺里進(jìn)行進(jìn)化，或者至少是在這里進(jìn)行停留和復(fù)制,。研究人員同時(shí)揭示出,，X4病毒并不是一直存在于身體里，而是在AIDS開始發(fā)作前由R5直接進(jìn)化而來,。此外,，研究人員還發(fā)現(xiàn)，雖然各個(gè)兒童的病史存在差異,，但是HIV在每個(gè)兒童體內(nèi)的進(jìn)化路徑卻很相似,。
Goodenow認(rèn)為，這表明HIV病毒的進(jìn)化路徑可能并不是完全隨機(jī)的,，它可能遵循一種設(shè)計(jì)好的發(fā)展程序,。
英國(guó)牛津大學(xué)動(dòng)物學(xué)系的Oliver Pybus表示，這是一項(xiàng)卓越的研究,，它表明了感染過程中HIV精密的進(jìn)化和改編模式,，并且第一次揭示了機(jī)體免疫細(xì)胞的運(yùn)作與病毒進(jìn)化之間的聯(lián)系。
Goodenow表示,，下一步的研究將是追蹤成人體內(nèi)HIV病毒在治療前后的變化情況,。他同時(shí)希望此次發(fā)現(xiàn)能夠有助于開發(fā)出一種新的藥物，以干擾HIV在胸腺里的進(jìn)化,。（科學(xué)網(wǎng) 梅進(jìn)/編譯）
原始出處:
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.
Received: April 6, 2007; Accepted: September 6, 2007; Published: September 26, 2007
