Interferon induced circRNAs escape herpesvirus host shutoff and suppress lytic infection

Sarah E Dremel, Takanobu Tagawa, Vishal N Koparde, Carmen Hernandez-Perez, Jesse H Arbuckle, Thomas M Kristie, Laurie T Krug, Joseph M Ziegelbauer

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

To globally profile circRNAs, we employ RNA-Sequencing paired with chimeric junction analysis for alpha-, beta-, and gamma-herpesvirus infection. We find circRNAs are, as a population, resistant to host shutoff. We validate this observation using ectopic expression assays of human and murine herpesvirus endoribonucleases. During lytic infection, four circRNAs are commonly induced across all subfamilies of human herpesviruses, suggesting a shared mechanism of regulation. We test one such mechanism, namely how interferon-stimulation influences circRNA expression. 67 circRNAs are upregulated by either interferon-β or -γ treatment, with half of these also upregulated during lytic infection. Using gain and loss of function studies we find an interferon-stimulated circRNA, circRELL1, inhibits lytic Herpes SimplexVirus-1 infection. We previously reported circRELL1 inhibits lytic Kaposi sarcoma-associated herpesvirus infection, suggesting a pan-herpesvirus antiviral activity. We propose a two-pronged model in which interferon-stimulated genes may encode both mRNA and circRNA with antiviral activity. This is critical in cases of host shutoff, such as alpha- and gamma-herpesvirus infection, where the mRNA products are degraded but circRNAs escape
Original languageEnglish
Pages (from-to)1541-1569
Number of pages29
JournalEMBO Reports
Volume25
Issue number3
Early online date23 Jan 2024
DOIs
Publication statusPublished - 12 Mar 2024
Externally publishedYes

Keywords / Materials (for Non-textual outputs)

  • Circular RNAs
  • Herpesviruses
  • Host Shutoff
  • Interferon-stimulated Genes

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