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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminopeptidases / antagonists & inhibitors*
  • Aminopeptidases / genetics
  • Aminopeptidases / physiology
  • Antigen Presentation
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Line
  • Cytomegalovirus / genetics*
  • Cytomegalovirus / immunology
  • Cytomegalovirus Infections / immunology
  • Down-Regulation
  • Humans
  • MicroRNAs / physiology*
  • Minor Histocompatibility Antigens
  • Ovalbumin / metabolism


  • MicroRNAs
  • Minor Histocompatibility Antigens
  • Ovalbumin
  • Aminopeptidases
  • ERAP1 protein, human