Transcriptional response to VZV infection is modulated by RNA polymerase III in lung epithelial cell lines

Brianna M. Doratt, Elizabeth Vance, Delphine C. Malherbe, Mark T.W. Ebbert, Ilhem Messaoudi

Research output: Contribution to journalArticlepeer-review

Abstract

Ancestral RNA polymerase III (Pol III) is a multi-subunit polymerase responsible for transcription of short non-coding RNA, such as double-stranded short interspersed nuclear elements (SINEs). Although SINE ncRNAs are generally transcriptionally repressed, they can be induced in response to viral infections and can stimulate immune signaling pathways. Indeed, mutations in RNA Pol III have been associated with poor antiviral interferon response following infection with varicella zoster virus (VZV). In this study, we probed the role of Pol III transcripts in the detection and initial immune response to VZV by characterizing the transcriptional response following VZV infection of wild type A549 lung epithelial cells as well as A549 cells lacking specific RNA sensors MAVS and TLR3, or interferon-stimulated genes RNase L and PKR in presence or absence of functional RNA Pol III. Multiple components of the antiviral sensing and interferon signaling pathways were involved in restricting VZV replication in lung epithelial cells thus suggesting an innate defense system with built-in redundancy. In addition, RNA Pol III silencing altered the antiviral transcriptional program indicating that it plays an essential role in the sensing of VZV infection.

Original languageEnglish
Article number943587
JournalFrontiers in Cellular and Infection Microbiology
Volume12
DOIs
StatePublished - Jul 25 2022

Bibliographical note

Funding Information:
This work was funded by NIH grant number R21AI143301.

Publisher Copyright:
Copyright © 2022 Doratt, Vance, Malherbe, Ebbert and Messaoudi.

Keywords

  • MAVS
  • PKR
  • RNA Polymerase III
  • RNA sensors
  • RNase L
  • VZV
  • antiviral innate immunity
  • transcriptome

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Microbiology (medical)
  • Infectious Diseases

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