Intrahepatic Transcriptional Signature Associated with Response to Interferon-α Treatment in the Woodchuck Model of Chronic Hepatitis B

PLoS Pathogens
Simon P FletcherStephan Menne

Abstract

Recombinant interferon-alpha (IFN-α) is an approved therapy for chronic hepatitis B (CHB), but the molecular basis of treatment response remains to be determined. The woodchuck model of chronic hepatitis B virus (HBV) infection displays many characteristics of human disease and has been extensively used to evaluate antiviral therapeutics. In this study, woodchucks with chronic woodchuck hepatitis virus (WHV) infection were treated with recombinant woodchuck IFN-α (wIFN-α) or placebo (n = 12/group) for 15 weeks. Treatment with wIFN-α strongly reduced viral markers in the serum and liver in a subset of animals, with viral rebound typically being observed following cessation of treatment. To define the intrahepatic cellular and molecular characteristics of the antiviral response to wIFN-α, we characterized the transcriptional profiles of liver biopsies taken from animals (n = 8-12/group) at various times during the study. Unexpectedly, this revealed that the antiviral response to treatment did not correlate with intrahepatic induction of the majority of IFN-stimulated genes (ISGs) by wIFN-α. Instead, treatment response was associated with the induction of an NK/T cell signature in the liver, as well as an intrahepatic IFN-γ transc...Continue Reading

References

Oct 5, 1990·Journal of Molecular Biology·S F AltschulD J Lipman
Mar 1, 1970·Journal of Molecular Biology·S B Needleman, C D Wunsch
Oct 6, 1999·Genome Research·X Huang, A Madan
Dec 29, 1999·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·P J CoteJ L Gerin
Jun 8, 2002·Veterinary Immunology and Immunopathology·Stephan MenneBud C Tennant
Sep 13, 2002·Journal of Medical Virology·Pedro BerraondoJuan Ruiz
Nov 16, 2002·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Valentina SalucciFabio Palombo
Apr 22, 2004·Proceedings of the National Academy of Sciences of the United States of America·Stefan WielandFrancis V Chisari
Jul 5, 2005·Proceedings of the National Academy of Sciences of the United States of America·Stefan F WielandFrancis V Chisari
Oct 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Aravind SubramanianJill P Mesirov
Nov 3, 2006·Journal of Virology·Michael D RobekFrancis V Chisari
Jan 9, 2007·World Journal of Gastroenterology : WJG·Stephan Menne, Paul J Cote
Apr 23, 2008·Current Protocols in Bioinformatics·Melissa de la Bastide, W Richard McCombie
Nov 19, 2008·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Pedro BerraondoGloria González-Aseguinolaza
Dec 31, 2008·BMC Bioinformatics·Peter Langfelder, Steve Horvath
Jan 1, 2009·Journal of Virology·Julien CrettazGloria Gonzalez-Aseguinolaza
Mar 6, 2009·Genome Biology·Ben LangmeadSteven L Salzberg
Jun 10, 2009·Bioinformatics·Heng LiUNKNOWN 1000 Genome Project Data Processing Subgroup
Sep 11, 2010·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Milan J SonneveldHarry L A Janssen
Oct 29, 2010·Genome Biology·Simon Anders, Wolfgang Huber
Mar 8, 2011·Gastroenterology·Marc LütgehetmannMaura Dandri
Mar 23, 2011·Nature Reviews. Gastroenterology & Hepatology·Hellan Kwon, Anna S Lok
May 17, 2011·Nature Biotechnology·Manfred G GrabherrAviv Regev
Jan 25, 2012·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Ning LiWei Liu
Feb 14, 2012·Current Opinion in Virology·John W Schoggins, Charles M Rice
Mar 21, 2012·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Simon P FletcherStephan Menne
Mar 24, 2012·Current Opinion in Virology·Melissa Swiecki, Marco Colonna
Jul 19, 2012·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Simon P FletcherStephan Menne
Dec 21, 2012·The Journal of Experimental Medicine·Dimitra PeppaMala K Maini

❮ Previous
Next ❯

Citations

Apr 17, 2016·Journal of Hepatology·Antonio Bertoletti, Carlo Ferrari
Apr 17, 2016·Journal of Hepatology·Mala K Maini, Adam J Gehring
Oct 24, 2017·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Fang ShenZhenghong Yuan
Aug 16, 2017·Scientific Reports·Martijn D B van de GardeThomas Vanwolleghem
Aug 29, 2019·Nature Reviews. Drug Discovery·Gregory C FanningAntonio Bertoletti
Jan 6, 2021·Proceedings of the National Academy of Sciences of the United States of America·Laura M BergnerDaniel G Streicker
Apr 26, 2020·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Jieliang ChenZhenghong Yuan
Feb 15, 2018·Current Opinion in Virology·Aleksei SuslovStephan Menne
Mar 18, 2021·Journal of Hepatocellular Carcinoma·Michal Mauda-HavakukWilliam F Pritchard
Jun 25, 2021·World Journal of Gastrointestinal Oncology·Manasa Suresh, Stephan Menne
Jan 19, 2021·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Xupeng HongJianming Hu
Aug 10, 2021·Frontiers in Immunology·Manasa SureshStephan Menne
Mar 12, 2019·Virology·Tetyana LukashSeverin O Gudima

❮ Previous
Next ❯

Methods Mentioned

BETA
transgenic
biopsy
RNA-Seq
biopsies
ELISA
flow cytometry
transfection
size exclusion chromatography
dot
PCR

Software Mentioned

SAMtools
GSEA
PHRAP
BLAST
CASAVA
DESeq
Ingenuity Pathway Analysis
Trinity
Partek Genomics
Ingenuity Pathway Analysis ( IPA )

Related Concepts

Related Feeds

Cancer Biology: Molecular Imaging

Molecular imaging enables noninvasive imaging of key molecules that are crucial to tumor biology. Discover the latest research in molecular imaging in cancer biology in this feed.

Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.