HIV-1 superinfection despite broad CD8+ T-cell responses containing replication of the primary virus
HIV-1 superinfection despite broad CD8+ T-cell responses containing replication of the primary virus
复制标题
DOI：
10.1038/nature01200
复制
发表时间：
2002-11-28
期刊：
影响因子：
64.8
通讯作者：
Walker, BD
中科院分区：
文献类型：
--
作者：
Altfeld, M;Allen, TM;Walker, BD
对急性HIV - 1感染进行早期治疗，随后中断治疗，已显示出增强对感染的免疫控制的潜力（1 - 3）。然而，随后控制的丧失使得保护性免疫的相关因素能够得到评估。在此我们表明，在一名感染HIV - 1的个体中，经过长时间的免疫抑制后，血浆病毒血症突然暴发，此时病毒蛋白Gag、RT、整合酶、Env、Nef、Vpr、Vif和Rev中的25个不同的CD8(+) T细胞表位正被靶向。对血浆和细胞中的病毒进行测序表明，感染第二种B亚型病毒与免疫控制的丧失同时发生。这种病毒血症的突然增加与一半的CD8(+) T细胞反应下降有关。下降的CD8(+) T细胞反应伴随着相对于初始病毒的序列变化，从而导致识别能力受损。我们的数据表明，在强烈且广泛定向的病毒特异性CD8(+) T细胞反应的情况下，HIV - 1重复感染可能发生。尽管持续识别多个CD8表位，但对密切相关的HIV - 1毒株缺乏交叉保护性免疫，这对公共卫生和疫苗开发具有重要意义。
Early treatment of acute HIV-1 infection followed by treatment interruptions has shown promise for enhancing immune control of infection(1-3). A subsequent loss of control, however, allows the correlates of protective immunity to be assessed. Here we show that sudden breakthrough of plasma viraemia occurred after prolonged immune containment in an individual infected with HIV-1 at a time when 25 distinct CD8(+) T-cell epitopes in the viral proteins Gag, RT, Integrase, Env, Nef, Vpr, Vif and Rev were being targeted. Sequencing of the virus in plasma and cells showed that superinfection with a second clade-B virus was coincident with the loss of immune control. This sudden increase in viraemia was associated with a decline in half of the CD8(+) T-cell responses. The declining CD8(+) T-cell responses were coupled with sequence changes relative to the initial virus that resulted in impaired recognition. Our data show that HIV-1 superinfection can occur in the setting of a strong and broadly directed virus-specific CD8(+) T-cell response. The lack of cross-protective immunity for closely related HIV-1 strains, despite persistent recognition of multiple CD8 epitopes, has important implications for public health and vaccine development.