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Host-derived circular RNAs display proviral activities in Hepatitis C virus-infected cells.
- Source :
-
PLoS pathogens [PLoS Pathog] 2020 Aug 07; Vol. 16 (8), pp. e1008346. Date of Electronic Publication: 2020 Aug 07 (Print Publication: 2020). - Publication Year :
- 2020
-
Abstract
- Viruses subvert macromolecular pathways in infected host cells to aid in viral gene amplification or to counteract innate immune responses. Roles for host-encoded, noncoding RNAs, including microRNAs, have been found to provide pro- and anti-viral functions. Recently, circular RNAs (circRNAs), that are generated by a nuclear back-splicing mechanism of pre-mRNAs, have been implicated to have roles in DNA virus-infected cells. This study examines the circular RNA landscape in uninfected and hepatitis C virus (HCV)-infected liver cells. Results showed that the abundances of distinct classes of circRNAs were up-regulated or down-regulated in infected cells. Identified circRNAs displayed pro-viral effects. One particular up-regulated circRNA, circPSD3, displayed a very pronounced effect on viral RNA abundances in both hepatitis C virus- and Dengue virus-infected cells. Though circPSD3 has been shown to bind factor eIF4A3 that modulates the cellular nonsense-mediated decay (NMD) pathway, circPSD3 regulates RNA amplification in a pro-viral manner at a post-translational step, while eIF4A3 exhibits the anti-viral property of the NMD pathway. Findings from the global analyses of the circular RNA landscape argue that pro-, and likely, anti-viral functions are executed by circRNAs that modulate viral gene expression as well as host pathways. Because of their long half-lives, circRNAs likely play hitherto unknown, important roles in viral pathogenesis.<br />Competing Interests: The authors have declared that no competing interests exist.
- Subjects :
- Carcinoma, Hepatocellular genetics
Carcinoma, Hepatocellular pathology
DEAD-box RNA Helicases genetics
DEAD-box RNA Helicases metabolism
Eukaryotic Initiation Factor-4A genetics
Eukaryotic Initiation Factor-4A metabolism
Gene Expression Profiling
Hepatitis C virology
Humans
Liver Neoplasms genetics
Liver Neoplasms pathology
Nonsense Mediated mRNA Decay
Viral Proteins genetics
Viral Proteins metabolism
Carcinoma, Hepatocellular virology
Hepacivirus genetics
Hepatitis C complications
Liver Neoplasms virology
Proviruses genetics
RNA, Circular genetics
RNA, Viral genetics
Virus Replication
Subjects
Details
- Language :
- English
- ISSN :
- 1553-7374
- Volume :
- 16
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- PLoS pathogens
- Publication Type :
- Academic Journal
- Accession number :
- 32764824
- Full Text :
- https://doi.org/10.1371/journal.ppat.1008346