Constraints on HIV-1 evolution and immunodominance revealed in monozygotic adult twins infected with the same virus.
Constraints on HIV-1 evolution and immunodominance revealed in monozygotic adult twins infected with the same virus.
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DOI：
10.1084/jem.20052116
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发表时间：
2006-03-20
期刊：
影响因子：
--
通讯作者：
Martinez-Picado J
中科院分区：
文献类型：
--
作者：
Draenert R;Allen TM;Liu Y;Wrin T;Chappey C;Verrill CL;Sirera G;Eldridge RL;Lahaie MP;Ruiz L;Clotet B;Petropoulos CJ;Walker BD;Martinez-Picado J
由于宿主和遗传病毒的多样性，在快速演变的人类病毒感染中病毒-宿主相互作用和疾病进展的可预测性一直难以评估。在这里，我们研究了适应性艾滋病毒特异性细胞和体液免疫反应和病毒进化的成年同卵双胞胎同时感染同一病毒。在三年的随访中，CD 4 T细胞计数和病毒载量遵循类似的轨迹。最初的CD 8 T细胞应答靶向17个表位，其中15个在每对双胞胎中是相同的，包括两个免疫显性应答。到感染后36个月，15个初始反应中的14个在两个中都仍然可以检测到，而所有新的反应都是亚显性的，并且仍然如此。在两对双胞胎中均下降的四种反应中，有三种在同一残基上表现出突变。此外，进化中的抗体反应交叉中和了另一个双胞胎的病毒，包膜基因的进化模式也发生了类似的变化。这些结果揭示了适应性细胞和体液免疫反应和HIV进化在相同的遗传环境中的相当一致性，表明对HIV免疫逃逸的突变途径的限制。
The predictability of virus–host interactions and disease progression in rapidly evolving human viral infections has been difficult to assess because of host and genetic viral diversity. Here we examined adaptive HIV-specific cellular and humoral immune responses and viral evolution in adult monozygotic twins simultaneously infected with the same virus. CD4 T cell counts and viral loads followed similar trajectories over three years of follow up. The initial CD8 T cell response targeted 17 epitopes, 15 of which were identical in each twin, including two immunodominant responses. By 36 months after infection, 14 of 15 initial responses were still detectable in both, whereas all new responses were subdominant and remained so. Of four responses that declined in both twins, three demonstrated mutations at the same residue. In addition, the evolving antibody responses cross-neutralized the other twin's virus, with similar changes in the pattern of evolution in the envelope gene. These results reveal considerable concordance of adaptive cellular and humoral immune responses and HIV evolution in the same genetic environment, suggesting constraints on mutational pathways to HIV immune escape.
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DOI：
10.1084/jem.185.8.1423
发表时间：
1997-04-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Goulder PJ;Sewell AK;Lalloo DG;Price DA;Whelan JA;Evans J;Taylor GP;Luzzi G;Giangrande P;Phillips RE;McMichael AJ
通讯作者：
McMichael AJ
HIV-1 GAG中的簇突变是逃避HLA-B27限制的细胞毒性T淋巴细胞反应所必需的。
影响因子：
15.3
作者：
Kelleher, A D;Long, C;Holmes, E C;Allen, R L;Wilson, J;Conlon, C;Workman, C;Shaunak, S;Olson, K;Goulder, P;Brander, C;Ogg, G;Sullivan, J S;Dyer, W;Jones, I;McMichael, A J;Rowland-Jones, S;Phillips, R E
通讯作者：
Phillips, R E
影响因子：
5.4
作者：
Kimura, Y;Gushima, T;Walker, CM
通讯作者：
Walker, CM
影响因子：
56.9
作者：
COFFIN, JM
通讯作者：
COFFIN, JM
影响因子：
5.4
作者：
AHMED, R;SIMON, RS;FREEDMAN, DM
通讯作者：
FREEDMAN, DM