Human cytomegalovirus induces and exploits Roquin to counteract the IRF1-mediated antiviral state

Jaewon Song, Sanghyun Lee, Dong Yeon Cho, Sungwon Lee, Hyewon Kim, Namhee Yu, Sanghyuk Lee, Kwangseog Ahn

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

RNA represents a pivotal component of host–pathogen interactions. Human cytomegalovirus (HCMV) infection causes extensive alteration in host RNA metabolism, but the functional relationship between the virus and cellular RNA processing remains largely unknown. Through loss-of-function screening, we show that HCMV requires multiple RNA-processing machineries for efficient viral lytic production. In particular, the cellular RNA-binding protein Roquin, whose expression is actively stimulated by HCMV, plays an essential role in inhibiting the innate immune response. Transcriptome profiling revealed Roquin-dependent global down-regulation of proinflammatory cytokines and antiviral genes in HCMV-infected cells. Furthermore, using cross-linking immunoprecipitation (CLIP)-sequencing (seq), we identified IFN regulatory factor 1 (IRF1), a master transcriptional activator of immune responses, as a Roquin target gene. Roquin reduces IRF1 expression by directly binding to its mRNA, thereby enabling suppression of a variety of antiviral genes. This study demonstrates how HCMV exploits host RNA-binding protein to prevent a cellular antiviral response and offers mechanistic insight into the potential development of CMV therapeutics.

Original languageEnglish
Pages (from-to)18619-18628
Number of pages10
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number37
DOIs
StatePublished - 10 Sep 2019

Keywords

  • Human cytomegalovirus
  • Immune evasion
  • Proinflammatory cytokine
  • RNA-binding protein

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