National Creative Research Initiative Center for Antigen Presentation, Department of Biological Sciences, Seoul National University, Seoul, Republic of Korea.
Nat Immunol. 2011 Sep 4;12(10):984-91. doi: 10.1038/ni.2097.
Major histocompatibility complex (MHC) class I molecules present peptides on the cell surface to CD8(+) T cells, which is critical for the killing of virus-infected or transformed cells. Precursors of MHC class I-presented peptides are trimmed to mature epitopes by the aminopeptidase ERAP1. The US2-US11 genomic region of human cytomegalovirus (HCMV) is dispensable for viral replication and encodes three microRNAs (miRNAs). We show here that HCMV miR-US4-1 specifically downregulated ERAP1 expression during viral infection. Accordingly, the trimming of HCMV-derived peptides was inhibited, which led to less susceptibility of infected cells to HCMV-specific cytotoxic T lymphocytes (CTLs). Our findings identify a previously unknown viral miRNA-based CTL-evasion mechanism that targets a key step in the MHC class I antigen-processing pathway.
主要组织相容性复合体 (MHC) Ⅰ类分子将肽呈递在细胞表面，供 CD8(+)T 细胞识别，这对于杀伤病毒感染或转化细胞至关重要。MHC Ⅰ类呈递肽的前体由氨肽酶 ERAP1 修剪成熟表位。人巨细胞病毒 (HCMV) 的 US2-US11 基因组区域对于病毒复制不是必需的，并且编码三个 microRNAs (miRNAs)。我们在这里表明，HCMV miR-US4-1 在病毒感染期间特异性地下调 ERAP1 的表达。相应地，HCMV 衍生肽的修剪受到抑制，导致感染细胞对 HCMV 特异性细胞毒性 T 淋巴细胞 (CTL) 的敏感性降低。我们的发现确定了一种以前未知的基于病毒 miRNA 的 CTL 逃逸机制，该机制靶向 MHC Ⅰ类抗原加工途径中的关键步骤。
