Heeregrave Edwin J, Geels Mark J, Brenchley Jason M, Baan Elly, Ambrozak David R, van der Sluis Renee M, Bennemeer Rune, Douek Daniel C, Goudsmit Jaap, Pollakis Georgios, Koup Richard A, Paxton William A
Laboratory of Experimental Virology, Department of Medical Microbiology, Center of Infection and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, The Netherlands.
Virology. 2009 Oct 10;393(1):24-32. doi: 10.1016/j.virol.2009.07.011. Epub 2009 Aug 20.
Viral compartmentalization between naïve and memory CD4(+) T cell subsets has been described, but only for individuals who were receiving antiretroviral therapy (ART). We present here an extensive analysis of the viral quasispecies residing in the naïve, central and effector memory CD4(+) T cell subsets in a number of therapy naïve individuals and representing an array of HIV-1 subtypes. We longitudinally analyzed subset-specific infection and evolution in a subtype B infected individual who switches from CCR5 to dual CCR5/CXCR4 coreceptor usage. We show that the central memory subset, the predominantly infected subset, harbors a more diverse viral population compared to the others. Through sequence analysis of the env C2V3 region we demonstrate a lack of viral compartmentalization among all subsets. Upon coreceptor switch we observe a pronounced increase in the infection level of the naïve population. Our findings emphasize the importance of all CD4(+) T cell subsets to viral evolution.
已有研究描述了初始和记忆性CD4(+) T细胞亚群之间的病毒区室化现象，但仅限于接受抗逆转录病毒疗法（ART）的个体。我们在此展示了对一些未经治疗的个体中初始、中央和效应记忆性CD4(+) T细胞亚群中病毒准种的广泛分析，这些个体代表了一系列HIV-1亚型。我们纵向分析了一名从使用CCR5共受体转换为使用CCR5/CXCR4双共受体的B亚型感染个体中特定亚群的感染和进化情况。我们发现，主要被感染的中央记忆亚群所携带的病毒群体比其他亚群更多样化。通过对env C2V3区域的序列分析，我们证明所有亚群之间不存在病毒区室化现象。在共受体转换后，我们观察到初始群体的感染水平显著增加。我们的研究结果强调了所有CD4(+) T细胞亚群对病毒进化的重要性。
