Hepatitis C Virus Infection Induces Hepatic Expression of NF-κB-Inducing Kinase and Lipogenesis by Downregulating miR-122

MBio
Brianna LoweyT Jake Liang

Abstract

Hepatitis C virus (HCV) harnesses host dependencies to infect human hepatocytes. We previously identified a pivotal role of IκB kinase α (IKK-α) in regulating cellular lipogenesis and HCV assembly. In this study, we defined and characterized NF-κB-inducing kinase (NIK) as an IKK-α upstream serine/threonine kinase in IKK-α-mediated proviral effects and the mechanism whereby HCV exploits this innate pathway to its advantage. We manipulated NIK expression in Huh7.5.1 cells through loss- and gain-of-function approaches and examined the effects on IKK-α activation, cellular lipid metabolism, and viral assembly. We demonstrated that NIK interacts with IKK-α to form a kinase complex in association with the stress granules, in which IKK-α is phosphorylated upon HCV infection. Depletion of NIK significantly diminished cytosolic lipid droplet content and impaired HCV particle production. NIK overexpression enhanced HCV assembly, and this process was abrogated in cells deprived of IKK-α, suggesting that NIK acts upstream of IKK-α. NIK abundance was increased in HCV-infected hepatocytes, liver tissues from Alb-uPA/Scid mice engrafted with human hepatocytes, and chronic hepatitis C patients. NIK mRNA contains an miR-122 seed sequence bindin...Continue Reading

References

Feb 19, 2000·Annals of Internal Medicine·T J LiangJ H Hoofnagle
May 15, 2002·Current Biology : CB·Mariana Lagos-QuintanaThomas Tuschl
Aug 19, 2005·Nature·Francis V Chisari
Sep 6, 2005·Science·Catherine L JoplingPeter Sarnow
Feb 7, 2006·Cell Metabolism·Christine EsauBrett P Monia
Dec 22, 2006·Nature Reviews. Molecular Cell Biology·Neil D Perkins
Feb 16, 2007·Journal of Virology·Takanobu KatoT Jake Liang
Aug 28, 2007·Nature Cell Biology·Yusuke MiyanariKunitada Shimotohno
Nov 26, 2008·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Onpan CheungArun J Sanyal
Jun 3, 2009·Genes & Development·David GatfieldUeli Schibler
Sep 1, 2009·Proceedings of the National Academy of Sciences of the United States of America·Qisheng LiStephen J Elledge
Dec 22, 2010·Cell Research·Shao-Cong Sun
Jan 19, 2011·Journal of Hepatology·Zhen-Ya LiChih-Chuan Liang
Jun 21, 2011·Annual Review of Microbiology·Catherine L Murray, Charles M Rice
Feb 4, 2012·Frontiers in Genetics·Yoshimasa SaitoToshifumi Hibi
Jul 24, 2012·The Journal of Clinical Investigation·Shu-Hao HsuKalpana Ghoshal
Jul 24, 2012·The Journal of Clinical Investigation·Wei-Chih TsaiAnn-Ping Tsou
Nov 23, 2012·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Khayriyyah Mohd HanafiahSteven T Wiersma
Dec 19, 2012·Proceedings of the National Academy of Sciences of the United States of America·You LiStanley M Lemon
May 17, 2013·The New England Journal of Medicine·T Jake Liang, Marc G Ghany
Oct 14, 2014·Journal of Hepatology·Simonetta BandieraMirjam B Zeisel
Mar 15, 2015·Cell·Joseph M LunaRobert B Darnell
Aug 8, 2015·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Hui WangUNKNOWN East-German and Swiss Hepatitis C Virus Study Groups
Jun 15, 2016·Proceedings of the National Academy of Sciences of the United States of America·Qisheng LiT Jake Liang
Aug 2, 2016·The International Journal of Biochemistry & Cell Biology·Ioanna VallianouMargarita Hadzopoulou-Cladaras
Sep 1, 2016·Annual Review of Virology·Peter Sarnow, Selena M Sagan
Apr 22, 2017·Nature Reviews. Gastroenterology & Hepatology·Nina L GluchowskiRobert V Farese
Jul 1, 2017·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Xiaoming ChengT Jake Liang

❮ Previous
Next ❯

Citations

Oct 28, 2019·International Journal of Molecular Sciences·Eckhard KlieserMatthias Ocker
Jun 18, 2020·International Journal of Molecular Sciences·Ariadna Pielok, Krzysztof Marycz
Nov 20, 2020·Journal of Virology·Yung-Ju YehJu-Chien Cheng

❮ Previous
Next ❯

Methods Mentioned

BETA
transfection
coimmunoprecipitation
nuclear
immunoprecipitation
co-IP
confocal microscopy
biopsy
PCR

Related Concepts

Related Feeds

Carcinoma, Hepatocellular

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

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.

Related Papers

The Journal of Immunology : Official Journal of the American Association of Immunologists
Bo ChenXueqin Liu
Biochimica Et Biophysica Acta. Reviews on Cancer
Gunter MaubachMichael Naumann
Trends in Molecular Medicine
Lara Valiño-RivasMaria Dolores Sanchez-Niño
© 2021 Meta ULC. All rights reserved