DHX9 regulates production of hepatitis B virus-derived circular RNA and viral protein levels

Oncotarget
Kazuma SekibaKazuhiko Koike

Abstract

Hepatitis B virus (HBV) infection, which is a major health concern worldwide, can lead to liver cirrhosis and hepatocellular carcinoma. Although current nucleos(t)ide analogs efficiently inhibit viral reverse transcription and viral DNA load clinically, episomal viral covalently closed circular DNA (cccDNA) minichromosomes and transcripts from cccDNA continue to be expressed over the long term. We hypothesized that, under these conditions, viral transcripts may have biological functions involved in pathogenesis. Here, we show that the host protein DExH-box helicase 9 (DXH9) is associated with viral RNAs. We also show that viral-derived circular RNA is produced during HBV replication, and the amount is increased by knockdown of the DHX9 protein, which, in turn, results in decreased viral protein levels but does not affect the levels of HBV DNA. These phenomena were observed in the HBV-producing cell culture model and HBV mini-circle model mimicking HBV cccDNA, as well as in human primary hepatocytes infected with HBV. Based on these results, we conclude that, in HBV infection, the RNA binding factor DHX9 is a novel regulator of viral circular RNA and viral protein levels.

References

Nov 1, 1976·Proceedings of the National Academy of Sciences of the United States of America·H L SangerA K Kleinschmidt
Oct 9, 1986·Nature·A KosH Schellekens
Feb 28, 1969·Journal of Molecular Biology·B Hirt
Mar 8, 2000·Microbiology and Molecular Biology Reviews : MMBR·C Seeger, W S Mason
Feb 28, 2003·The New England Journal of Medicine·Stephanos J HadziyannisUNKNOWN Adefovir Dipivoxil 438 Study Group
Feb 14, 2006·Journal of Hepatology·Chihiro YamasakiKatsutoshi Yoshizato
Sep 29, 2006·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Masaya SugiyamaMasashi Mizokami
Dec 5, 2008·The New England Journal of Medicine·Patrick MarcellinFranck Rousseau
Feb 17, 2009·Lancet·Yun-Fan Liaw, Chia-Ming Chu
Jul 6, 2010·Journal of Virological Methods·Thomas B Lentz, Daniel D Loeb
Dec 24, 2010·Journal of Gastroenterology and Hepatology·Kazuaki ChayamaMichio Imamura
Jun 16, 2011·The Journal of Infectious Diseases·Masataka TsugeKazuaki Chayama
Mar 1, 2013·Nature·Sebastian MemczakNikolaus Rajewsky
May 9, 2014·Nature Biotechnology·William R Jeck, Norman E Sharpless
Oct 5, 2014·Genes & Development·Dongming Liang, Jeremy E Wilusz
Mar 17, 2016·Scientific Reports·Akemi TakataKazuhiko Koike
May 27, 2016·Journal of Human Genetics·Motoyuki OtsukaKazuhiko Koike
Oct 5, 2016·JCI Insight·Takahiro KishikawaKazuhiko Koike
Mar 28, 2017·Molecular Cell·Nagarjuna Reddy PamudurtiSebastian Kadener
Jun 11, 2017·Journal of Hepatology·Marion DuriezPatrick Soussan

❮ Previous
Next ❯

Citations

Dec 27, 2018·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Kazuma SekibaKazuhiko Koike
Nov 26, 2020·The FEBS Journal·Ke-En Tan, Yat-Yuen Lim
Feb 25, 2021·The Journal of Microbiology·Zhihao LouBaolei Jia
Mar 7, 2021·Viruses·Rui-Zhu ShiLi Xing
Nov 3, 2020·Virus Research·Fan Guo, Li Xing
May 8, 2021·Frontiers in Microbiology·Janardhan AvilalaZhen Lin
May 19, 2021·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·Mengmei YangYunzhang Hu
Aug 8, 2021·International Journal of Molecular Sciences·Valeria PietropaoloUgo Moens
Aug 28, 2021·Cells·Xianhui ZengJinhang Gao
Nov 3, 2020·Virus Research·He XieLimin Chen

❮ Previous
Next ❯

Methods Mentioned

BETA
immunoprecipitation
electrophoresis
PCR
reverse transcription-PCR
transfection
RNA-immunoprecipitation
pull-down
immunoprecipitations
RIP
Assay

Software Mentioned

TurboSEQUEST
MASCOT
QuantaSoft

Related Concepts

Related Feeds

Adrenocortical Carcinoma

Hepatocellular carcinoma is the most common type of primary liver cancer and frequently occurs in individuals with chronic liver diseases like cirrhosis. Here is the latest research.

Carcinoma, Hepatocellular

Hepatocellular Carcinoma is a malignant cancer in liver epithelial cells. Discover the latest research on Hepatocellular Carcinoma here.