G-quadruplexes formed by Varicella-Zoster virus reiteration sequences suppress expression of glycoprotein C and regulate viral cell-to-cell spread

G-quadruplex (G4) formed by repetitive guanosine-rich sequences plays important roles in diverse cellular processes; however, its roles in viral infection are not fully understood. In this study, we investigated the genome-wide distribution of G4-forming sequences (G4 motifs) in Varicella-Zoster vir...

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Bibliographic Details
Published in:PLoS pathogens 2023-01, Vol.19 (1), p.e1011095-e1011095
Main Authors: Chung, Woo-Chang, Ravichandran, Subramaniyam, Park, Daegyu, Lee, Gwang Myeong, Kim, Young-Eui, Choi, Youngju, Song, Moon Jung, Kim, Kyeong Kyu, Ahn, Jin-Hyun
Format: Article
Language:English
Subjects:
Biology and Life Sciences
Chicken pox
Circular Dichroism
Dichroism
Electrophoresis
G-Quadruplexes
Gel electrophoresis
Gene expression
Genetic aspects
Genome
Genomes
Glycoprotein C
Glycoproteins
Health aspects
Herpes viruses
Herpesvirus 3, Human - genetics
Host-virus relationships
Infections
Oligonucleotides
Polyacrylamide
Research and Analysis Methods
Spectroscopy
Transfection
Varicella
Varicella-zoster virus
Viral Envelope Proteins - genetics
Viruses
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Summary:G-quadruplex (G4) formed by repetitive guanosine-rich sequences plays important roles in diverse cellular processes; however, its roles in viral infection are not fully understood. In this study, we investigated the genome-wide distribution of G4-forming sequences (G4 motifs) in Varicella-Zoster virus (VZV) and found that G4 motifs are enriched in the internal repeat short and the terminal repeat short regions flanking the unique short region and also in some reiteration (R) sequence regions. A high density of G4 motifs in the R2 region was found on the template strand of ORF14, which encodes glycoprotein C (gC), a virulent factor for viral growth in skin. Analyses such as circular dichroism spectroscopy, thermal difference spectra, and native polyacrylamide gel electrophoresis with oligodeoxynucleotides demonstrated that several G4 motifs in ORF14 form stable G4 structures. In transfection assays, gC expression from the G4-disrupted ORF14 gene was increased at the transcriptional level and became more resistant to suppression by G4-ligand treatment. The recombinant virus containing the G4-disrupted ORF14 gene expressed a higher level of gC mRNA, while it showed a slightly reduced growth. This G4-disrupted ORF14 virus produced smaller plaques than the wild-type virus. Our results demonstrate that G4 formation via reiteration sequences suppresses gC expression during VZV infection and regulates viral cell-to-cell spread.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1011095