Sun Jianping, Zhao Yan, Peng Yanchun, Han Zhen, Liu Guihai, Qin Ling, Liu Sai, Sun Huanhuan, Wu Hao, Dong Tao, Zhang Yonghong
Beijing You'An Hospital, Capital Medical University, Beijing, PR China Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford University, Oxford, UK.
Medicine (Baltimore). 2016 Jul;95(30):e4429. doi: 10.1097/MD.0000000000004429.
Cytotoxic T lymphocyte (CTL) responses play pivotal roles in controlling the replication of human immunodeficiency virus type 1 (HIV-1), but the correlation between CTL responses and the progression of HIV-1 infection are controversial on account of HIV immune escape mutations driven by CTL pressure were reported.The acute HIV-1-infected patients from Beijing were incorporated into our study to investigate the effects of CTL response on the progression of HIV-1 infection.A longitudinal study was performed on acute HIV-1-infected patients to clarify the kinetic of T-cell responses, the dynamic of escape mutations, as well as the correlation between effective T-cell response and the progression of HIV infection.Seven human leukocyte antigen-B51+ (HLA-B51+) individuals were screened from 105 acute HIV-1 infectors. The detailed kinetic of HLA-B51-restricted CTL responses was described through blood sampling time points including seroconversion, 3 and 6 months after HIV-1 infection in the 7 HLA-B51+ individuals, by using 16 known HLA-B51 restricted epitopes. Pol743-751 (LPPVVAKEI, LI9), Pol283-289 (TAFTIPSI, TI8), and Gag327-3459 (NANPDCKTI, NI9) were identified as 3 dominant epitopes, and ranked as starting with LI9, followed by TI8 and NI9 in the ability to induce T-cell responses. The dynamics of escape mutations in the 3 epitopes were also found with the same order as T-cell response, by using sequencing for viral clones on blood sampling at seroconversion, 3 and 6 months after HIV-1 infection.We use solid evidence to demonstrate the correlation between T-cell response and HIV-1 mutation, and postulate that multiple T-cell responses might benefit the control of HIV-1 infection, especially in acute infection phase.
细胞毒性T淋巴细胞(CTL)反应在控制1型人类免疫缺陷病毒(HIV-1)复制中起关键作用,但由于有报道称CTL压力会导致HIV免疫逃逸突变,CTL反应与HIV-1感染进展之间的相关性存在争议。将来自北京的急性HIV-1感染患者纳入我们的研究,以调查CTL反应对HIV-1感染进展的影响。对急性HIV-1感染患者进行了一项纵向研究,以阐明T细胞反应的动力学、逃逸突变的动态变化,以及有效的T细胞反应与HIV感染进展之间的相关性。从105名急性HIV-1感染者中筛选出7名人类白细胞抗原B51+(HLA-B51+)个体。通过在7名HLA-B51+个体中于HIV-1感染后的血清转化期、3个月和6个月等采血时间点,利用16个已知的HLA-B51限制性表位,描述了HLA-B51限制性CTL反应的详细动力学。Pol743-751(LPPVVAKEI,LI9)、Pol283-289(TAFTIPSI,TI8)和Gag327-3459(NANPDCKTI,NI9)被确定为3个优势表位,在诱导T细胞反应的能力方面,排名依次为LI9第一,其次是TI8和NI9。通过对HIV-1感染后血清转化期、3个月和6个月采血时的病毒克隆进行测序,还发现了这3个表位中逃逸突变的动态变化顺序与T细胞反应相同。我们用确凿的证据证明了T细胞反应与HIV-1突变之间的相关性,并推测多种T细胞反应可能有利于控制HIV-1感染,尤其是在急性感染期。