Infection-Induced Retrotransposon-Derived Noncoding RNAs Enhance Herpesviral Gene Expression via the NF-κB Pathway

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Short interspersed nuclear elements (SINEs) are noncoding mobile genetic elements that are present at ~106 copies per mammalian genome, roughly comprising 10% of mammalian genomic real estate. SINEs are typically transcriptionally silenced, though in some cases viral infection can promote their expression, yet to an unknown functional outcome. Thus, SINE elements represent the largest class of infection-inducible noncoding RNAs that are functionally uncharacterized. Here, we reveal that SINE RNAs play a critical role in the host-pathogen interaction in that they are required for efficient murine gammaherpesvirus 68 (MHV68) replication and gene expression. We demonstrate that SINE RNAs, both exogenously expressed and infection-induced, are robust activators of the IKKβ kinase, a key signaling molecule in the innate immune response. Activation of the IKKβ kinase by SINE RNA is mediated through both MAVS-dependent and independent mechanisms. Moreover, we demonstrate the activation of the IKKβ via SINE RNA is required to drive the phosphorylation of MHV68 RTA, the main viral transcriptional activator, which enhances its transcriptional activating property. Collectively, we reveal the first example of a role for SINE RNAs in the host-pathogen interaction and identify them as a key immune signaling molecule early during infection. Though SINE RNAs activate the innate immune response, MHV68 has co-opted SINE-mediate innate immune activation to enhance the viral lifecycle.

Vyšlo v časopise: Infection-Induced Retrotransposon-Derived Noncoding RNAs Enhance Herpesviral Gene Expression via the NF-κB Pathway. PLoS Pathog 11(11): e32767. doi:10.1371/journal.ppat.1005260
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005260

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