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RNA triphosphatase DUSP11 enables exonuclease XRN-mediated restriction of hepatitis C virus.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2018 Aug 07; Vol. 115 (32), pp. 8197-8202. Date of Electronic Publication: 2018 Jul 23. - Publication Year :
- 2018
-
Abstract
- Seventy percent of people infected with hepatitis C virus (HCV) will suffer chronic infection, putting them at risk for liver disease, including hepatocellular carcinoma. The full range of mechanisms that render some people more susceptible to chronic infection and liver disease is still being elucidated. XRN exonucleases can restrict HCV replication and may help to resolve HCV infections. However, it is unknown how 5' triphosphorylated HCV transcripts, primary products of the viral polymerase, become susceptible to attack by 5' monophosphate-specific XRNs. Here, we show that the 5' RNA triphosphatase DUSP11 acts on HCV transcripts, rendering them susceptible to XRN-mediated attack. Cells lacking DUSP11 show substantially enhanced HCV replication, and this effect is diminished when XRN expression is reduced. MicroRNA-122 (miR-122), a target of current phase II anti-HCV drugs, is known to protect HCV transcripts against XRNs. We show that HCV replication is less dependent on miR-122 in cells lacking DUSP11. Combined, these results implicate DUSP11 as an important component of XRN-mediated restriction of HCV.<br />Competing Interests: The authors declare no conflict of interest.
- Subjects :
- Acid Anhydride Hydrolases genetics
Carcinoma, Hepatocellular genetics
Carcinoma, Hepatocellular virology
Cell Line, Tumor
Dual-Specificity Phosphatases genetics
Exoribonucleases genetics
Gene Knockout Techniques
Genome, Viral
Hepacivirus physiology
Hepatitis C, Chronic genetics
Hepatitis C, Chronic virology
Hepatocytes virology
Humans
Liver Neoplasms genetics
Liver Neoplasms virology
RNA, Small Interfering metabolism
RNA, Viral metabolism
Virus Replication genetics
Acid Anhydride Hydrolases metabolism
Dual-Specificity Phosphatases metabolism
Exoribonucleases metabolism
Hepacivirus pathogenicity
Host-Pathogen Interactions physiology
MicroRNAs metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 115
- Issue :
- 32
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 30038017
- Full Text :
- https://doi.org/10.1073/pnas.1802326115