Temporal Landscape of MicroRNA-Mediated Host-Virus Crosstalk during Productive Human Cytomegalovirus Infection

Cell Host Microbe. 2015 Jun 10;17(6):838-51. doi: 10.1016/j.chom.2015.05.014.

Abstract

Temporal profiles of miRNA activity during productive virus infection can provide fundamental insights into host-virus interactions. Most reported miRNA targetome analyses in the context of virus infection have been performed in latently infected cells and lack reliable models for quantifying the suppression efficacy at specific miRNA target sites. Here, we identified highly competent temporal miRNA targetomes during lytic HCMV infection by using AGO-CLIP-seq together with a bioinformatic method that quantifies miRNA functionality at a specific target site, called ACE-scoring. The repression efficiency at target sites correlates with the magnitude of the ACE-score, and temporal HCMV-encoded miRNA targetomes identified by ACE-scoring were significantly enriched in functional categories involved in pathways central for HCMV biology. Furthermore, comparative analysis between human and viral miRNA targetomes supports the existence of intimate cooperation and co-targeting between them. Our holistic survey provides a valuable resource for understanding host-virus interactions during lytic HCMV infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cytomegalovirus / genetics*
  • Cytomegalovirus / pathogenicity
  • Cytomegalovirus Infections / virology*
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Viral*
  • HeLa Cells / virology
  • Host-Pathogen Interactions*
  • Humans
  • Interferons / metabolism
  • Janus Kinases / metabolism
  • MicroRNAs* / genetics
  • Reproducibility of Results
  • STAT Transcription Factors / metabolism
  • Sequence Analysis, RNA / methods
  • Signal Transduction / genetics

Substances

  • MicroRNAs
  • STAT Transcription Factors
  • Interferons
  • Janus Kinases

Associated data

  • GEO/GSE63797