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

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Title
Human cytomegalovirus induces and exploits Roquin to counteract the IRF1-mediated antiviral state
Author(s)
Jaewon Song; Sanghyun Lee; Dong-Yeon Cho; Sungwon Lee; Hyewon Kim; Namhee Yu; Sanghyuk Lee; Kwangseog Ahn
Publication Date
2019-09
Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v.116, no.37, pp.18619 - 18628
Publisher
NATL ACAD SCIENCES
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 downregulation 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. © 2019 National Academy of Sciences.
URI
https://pr.ibs.re.kr/handle/8788114/6880
ISSN
0027-8424
Appears in Collections:
Center for RNA Research(RNA 연구단) > Journal Papers (저널논문)
Files in This Item:
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