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Nat Immunol. 2011 Sep 4;12(10):984-91. doi: 10.1038/ni.2097.

Human cytomegalovirus microRNA miR-US4-1 inhibits CD8(+) T cell responses by targeting the aminopeptidase ERAP1.

Author information

1
National Creative Research Initiative Center for Antigen Presentation, Department of Biological Sciences, Seoul National University, Seoul, Republic of Korea.

Abstract

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.

PMID:
21892175
PMCID:
PMC3526977
DOI:
10.1038/ni.2097
[Indexed for MEDLINE]
Free PMC Article

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