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Human cytomegalovirus microRNA miR-US4-1 inhibits CD8 + T cell responses by targeting the aminopeptidase ERAP1
Cited 136 time in
Web of Science
Cited 150 time in Scopus
- Authors
- Issue Date
- 2011-10
- Publisher
- Nature Publishing Group
- Citation
- Nature Immunology, Vol.12 No.10, pp.984-991
- 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.
- ISSN
- 1529-2908
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