title: Infection-Induced Retrotransposon-Derived Noncoding RNAs Enhance Herpesviral Gene Expression via the NF-κB Pathway.
abstract: Short interspersed nuclear elements (SINEs) are highly abundant, RNA polymerase III-transcribed noncoding retrotransposons that are silenced in somatic cells but activated during certain stresses including viral infection. How these induced SINE RNAs impact the host-pathogen interaction is unknown. Here we reveal that during murine gammaherpesvirus 68 (MHV68) infection, rapidly induced SINE RNAs activate the antiviral NF-κB signaling pathway through both mitochondrial antiviral-signaling protein (MAVS)-dependent and independent mechanisms. However, SINE RNA-based signaling is hijacked by the virus to enhance viral gene expression and replication. B2 RNA expression stimulates IKKβ-dependent phosphorylation of the major viral lytic cycle transactivator protein RTA, thereby enhancing its activity and increasing progeny virion production. Collectively, these findings suggest that SINE RNAs participate in the innate pathogen response mechanism, but that herpesviruses have evolved to co-opt retrotransposon activation for viral benefit.
authors.affiliation: Department of Plant and Microbial Biology, University of California, Berkeley, Berkeley, California, United States of America.
authors.forename: John
authors.initials: J
authors.lastname: Karijolich
authors.affiliation: Department of Plant and Microbial Biology, University of California, Berkeley, Berkeley, California, United States of America.
authors.forename: Emma
authors.initials: E
authors.lastname: Abernathy
authors.affiliation: Department of Plant and Microbial Biology, University of California, Berkeley, Berkeley, California, United States of America.|Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California, United States of America.|Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, California, United States of America.
authors.forename: Britt A
authors.initials: BA
authors.lastname: Glaunsinger
mesh_terms: D000818:Animals; D002460:Cell Line; D015870:Gene Expression / Q000235:genetics; D015967:Gene Expression Regulation, Viral / Q000235:genetics*; D054884:Host-Pathogen Interactions; D051550:I-kappa B Kinase / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D022661:RNA, Untranslated / Q000235:genetics*; D012367:RNA, Viral / Q000235:genetics*; D018626:Retroelements; D018144:Rhadinovirus / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D014775:Virus Activation / Q000235:genetics*; D017735:Virus Latency / Q000235:genetics; D014779:Virus Replication / Q000235:genetics
chemical_list: D016328:NF-kappa B; D022661:RNA, Untranslated; D012367:RNA, Viral; D018626:Retroelements; D051550:I-kappa B Kinase