Human cytomegalovirus induces and exploits Roquin to counteract the IRF1-mediated antiviral state
- 주제(키워드) human cytomegalovirus , RNA-binding protein , immune evasion , proinflammatory cytokine
- 주제(기타) Multidisciplinary Sciences
- 등재 SCIE, SCOPUS
- OA유형 Green Published, Bronze
- 발행기관 NATL ACAD SCIENCES
- 발행년도 2019
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000161458
- 본문언어 영어
- Published As http://dx.doi.org/10.1073/pnas.1909314116
- PubMed https://pubmed.ncbi.nlm.nih.gov/31451648
초록/요약
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.
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