Hepatitis C Virus Activates a Neuregulin-Driven Circuit to Modify Surface Expression of Growth Factor Receptors of the ErbB Family

PloS One
Sabine StindtJohannes G Bode

Abstract

Recently, the epidermal growth factor (EGF) receptor (EGFR), a member of the ErbB receptor family, and its down-stream signalling have been identified as co-factors for HCV entry and replication. Since EGFR also functions as a heterodimer with other ErbB receptor family members, the subject of the present study was to investigate a possible viral interference with these cellular components. By using genotype 1b replicon cells as well as an infection-based system we found that while transcript and protein levels of EGFR and ErbB2 were up-regulated or unaffected, respectively, HCV induced a substantial reduction of ErbB3 and ErbB4 expression. Down-regulation of ErbB3 expression by HCV involves specificity protein (Sp)1-mediated induction of Neuregulin (NRG)1 expression as well as activation of Akt. Consistently, at transcript level disruption of ErbB3 expression by HCV can be prevented by knockdown of NRG1 or Sp1 expression, whereas reconstitution of ErbB3 protein levels requires inhibition of HCV-induced NRG1 expression and of Akt activity. Interestingly, the NRG1-mediated suppression of ErbB3 expression by HCV results in an enhanced expression of EGFR and ErbB2 on the cell surface, which can be mimicked by siRNA-mediated knockd...Continue Reading

References

Nov 26, 1999·Gene·G Suske
Mar 22, 2002·Journal of Virology·Thomas PietschmannRalf Bartenschlager
Nov 20, 2002·Journal of Virology·Keril J BlightCharles M Rice
Mar 22, 2003·Experimental Cell Research·Douglas L Falls
May 3, 2006·Proceedings of the National Academy of Sciences of the United States of America·Thomas PietschmannRalf Bartenschlager
Jul 11, 2006·Nature Reviews. Molecular Cell Biology·Ami Citri, Yosef Yarden
Aug 3, 2007·The Journal of Clinical Investigation·Hongtao ZhangMark I Greene
Sep 21, 2007·Journal of Virology·Artur KaulRalf Bartenschlager
Dec 18, 2007·Biochimica Et Biophysica Acta·Timo FrensingThomas Schmitt-John
Aug 21, 2008·Biological Chemistry·Johannes G BodeDieter Häussinger
May 29, 2009·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Erwin Daniel BrenndörferJohannes Georg Bode
Aug 1, 2009·Biological Chemistry·Johannes G BodeDieter Häussinger
Jun 30, 2012·Nature Methods·Johannes SchindelinAlbert Cardona
Oct 26, 2012·The Journal of Biological Chemistry·Zhe LiuJing-hsiung James Ou
Mar 5, 2013·Biochemical and Biophysical Research Communications·Nogol RahbinErwin Daniel Brenndörfer
May 2, 2013·PLoS Pathogens·Katja MöllekenJohannes H Hegemann
Aug 2, 2013·Journal of Pharmacological Sciences·Nobuhiro OsadaYoshihisa Ito
Jan 21, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Erwin Daniel BrenndörferMatti Sällberg
Apr 3, 2014·Journal of Cellular Physiology·Smita Awasthi, Anne W Hamburger
Aug 8, 2014·Membranes·Vibeke Bertelsen, Espen Stang
Jan 7, 2015·Cellular Signalling·Christian EhltingJohannes G Bode

❮ Previous
Next ❯

Citations

Aug 16, 2016·Journal of Experimental & Clinical Cancer Research : CR·Corina ButaChristèle Desbois-Mouthon
Aug 16, 2018·MBio·Tonya N WatkinsVincent M Bruno
Feb 6, 2021·Journal of Clinical Medicine·Tom Domovitz, Meital Gal-Tanamy

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR
transfection
electrophoresis
ELISA
FACS
FCS

Software Mentioned

Fiji
FlowJo
SPSS
ImageJ

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.