Human cytomegalovirus induces and exploits Roquin to counteract the IRF1-mediated antiviral state.
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.
['Song|Jaewon|J|', 'Lee|Sanghyun|S|', 'Cho|Dong-Yeon|DY|', 'Lee|Sungwon|S|', 'Kim|Hyewon|H|', 'Yu|Namhee|N|', 'Lee|Sanghyuk|S|', 'Ahn|Kwangseog|K|']
D045744:Cell Line, Tumor D002478:Cells, Cultured D016207:Cytokines D003587:Cytomegalovirus D003586:Cytomegalovirus Infections D015536:Down-Regulation D005347:Fibroblasts D020869:Gene Expression Profiling D054884:Host-Pathogen Interactions D006801:Humans D057131:Immune Evasion D007113:Immunity, Innate D050856:Interferon Regulatory Factor-1 D061251:Primary Cell Culture D012333:RNA, Messenger D016601:RNA-Binding Proteins D044767:Ubiquitin-Protein Ligases D014779:Virus Replication
human cytomegalovirus RNA-binding protein proinflammatory cytokine immune evasion