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

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 in...

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Published in:Frontiers in cellular and infection microbiology 2022-07, Vol.12, p.943587-943587
Main Authors: Doratt, Brianna M, Vance, Elizabeth, Malherbe, Delphine C, Ebbert, Mark T W, Messaoudi, Ilhem
Format: Article
Language:English
Subjects:
antiviral innate immunity
Cellular and Infection Microbiology
Epithelial Cells
Herpesvirus 3, Human - genetics
Interferons
Lung
RNA
RNA Polymerase III
RNA Polymerase III - genetics
RNA sensors
RNase L
transcriptome
Virus Replication
VZV
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Summary: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.
ISSN:2235-2988
2235-2988
DOI:10.3389/fcimb.2022.943587