O'Connell Karen A, Xu Jie, Durbin Anna P, Apuzzo Linda G, Imteyaz Hejab, Williams Thomas M, Ray Stuart C, Margolick Joseph B, Siliciano Robert F, Blankson Joel N
Department of Medicine, School of Medicine, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205, USA.
J Infect Dis. 2009 Dec 15;200(12):1820-4. doi: 10.1086/648377.
The human immunodeficiency virus type 1 (HIV-1)-specific immune responses of patients with the HLA-B57/5801 alleles who spontaneously control viral replication serve as an important model for T cell-based HIV-1 vaccines. Determining the breadth of this response and the extent of virologic escape in primary infection in these patients is therefore critical. Here we document the development of mutations in 3 HLA-B5801-restricted epitopes in gag, nef, and pol in an HLA-B5801-positive patient who had a viral load of only 1159 copies/mL at day 167 after infection. A full genome sequence analysis was performed to determine the extent of mutations in HLA-B5801-restricted epitopes, and longitudinal sequence data of specific genes were combined with enzyme-linked immunospot assay analysis of critical epitopes to determine the importance of escape mutations. Thus, relative control of viral replication can be maintained in spite of the rapid development of multiple escape mutations within cytotoxic T lymphocyte epitopes.
人类免疫缺陷病毒1型（HIV-1）特异性免疫反应在自发控制病毒复制的携带HLA-B57/5801等位基因的患者中发挥作用，这是基于T细胞的HIV-1疫苗的重要模型。因此，确定这些患者在初次感染时这种反应的广度以及病毒学逃逸的程度至关重要。在此，我们记录了一名HLA-B5801阳性患者在感染后第167天病毒载量仅为1159拷贝/毫升时，gag、nef和pol中3个HLA-B5801限制性表位发生的突变情况。进行了全基因组序列分析以确定HLA-B5801限制性表位的突变程度，并将特定基因的纵向序列数据与关键表位的酶联免疫斑点分析相结合，以确定逃逸突变的重要性。因此，尽管在细胞毒性T淋巴细胞表位内多个逃逸突变迅速出现，但病毒复制仍可得到相对控制。
