title: Human cytomegalovirus microRNA miR-US4-1 inhibits CD8(+) T cell responses by targeting the aminopeptidase ERAP1.
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.
authors: National Creative Research Initiative Center for Antigen Presentation, Department of Biological Sciences, Seoul National University, Seoul, Republic of Korea.
authors: Sungchul
authors: S
authors: Kim
authors: Sanghyun
authors: S
authors: Lee
authors: Jinwook
authors: J
authors: Shin
authors: Youngkyun
authors: Y
authors: Kim
authors: Irini
authors: I
authors: Evnouchidou
authors: Donghyun
authors: D
authors: Kim
authors: Young-Kook
authors: YK
authors: Kim
authors: Young-Eui
authors: YE
authors: Kim
authors: Jin-Hyun
authors: JH
authors: Ahn
authors: Stanley R
authors: SR
authors: Riddell
authors: Efstratios
authors: E
authors: Stratikos
authors: V Narry
authors: VN
authors: Kim
authors: Kwangseog
authors: K
authors: Ahn
mesh_terms: D000626:Aminopeptidases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D017951:Antigen Presentation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D003587:Cytomegalovirus / Q000235:genetics* / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000276:immunology; D015536:Down-Regulation; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D015778:Minor Histocompatibility Antigens; D010047:Ovalbumin / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D015778:Minor Histocompatibility Antigens; D010047:Ovalbumin; D000626:Aminopeptidases; C464841:ERAP1 protein, human