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

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.

Varicella‐zoster virus‐related neurological complications: From infection to immunomodulatory therapies

“…96 The CNS is monitored for signs of injury or pathogens, proinflammatory cytokines are activated and produced, viral growth is limited and mortality is decreased, T cells trigger the mediate synaptic elimination of the pathogen, antigen is presented to T cells during CNS infection, and the phenotypic transformation from the proinflammatory M1-phenotype to the anti-inflammatory M2-phenotype can help resolve neuroinflammation and repair tissue. [97][98][99][100] T lymphocytes, monocytes, and DCs have been seen to enter the neurological system after VZV infection. 101 Although precise evidence on their involvement in VZV infection is few, research on other viral infections sheds light on these immune cells' roles in the immune system's reaction to viral invasion in the nervous system.…”

“…On the other hand, research on different viral infections sheds light on the roles played by microglia in the immune system's response to viral invasion in the neurological system 96 . The CNS is monitored for signs of injury or pathogens, proinflammatory cytokines are activated and produced, viral growth is limited and mortality is decreased, T cells trigger the mediate synaptic elimination of the pathogen, antigen is presented to T cells during CNS infection, and the phenotypic transformation from the pro‐inflammatory M1‐phenotype to the anti‐inflammatory M2‐phenotype can help resolve neuroinflammation and repair tissue 97‐100 …”