Persistent and transient replication of full-length hepatitis C virus genomes in cell culture

Journal of Virology
Thomas PietschmannRalf Bartenschlager

Abstract

The recently developed subgenomic hepatitis C virus (HCV) replicons were limited by the fact that the sequence encoding the structural proteins was missing. Therefore, important information about a possible influence of these proteins on replication and pathogenesis and about the mechanism of virus formation could not be obtained. Taking advantage of three cell culture-adaptive mutations that enhance RNA replication synergistically, we generated selectable full-length HCV genomes that amplify to high levels in the human hepatoma cell line Huh-7 and can be stably propagated for more than 6 months. The structural proteins are efficiently expressed, with the viral glycoproteins E1 and E2 forming heterodimers which are stable under nondenaturing conditions. No disulfide-linked glycoprotein aggregates were observed, suggesting that the envelope proteins fold productively. Electron microscopy studies indicate that cell lines harboring these full-length HCV RNAs contain lipid droplets. The majority of the core protein was found on the surfaces of these structures, whereas the glycoproteins appear to localize to the endoplasmic reticulum and cis-Golgi compartments. In agreement with this distribution, no endoglycosidase H-resistant for...Continue Reading

References

Jan 1, 1992·Medical Microbiology and Immunology·R ThomssenA Uy
Jul 1, 1991·Journal of Medical Virology·D BradleyE H Cook
Mar 26, 1982·Science·J HollandS VandePol
Oct 4, 1995·Biochemical and Biophysical Research Communications·D W KimJ Choe
Jun 1, 1994·Journal of Virology·E SantoliniN La Monica
Jan 1, 1997·Journal of Virology·V DeleersnyderJ Dubuisson
Feb 18, 1997·Proceedings of the National Academy of Sciences of the United States of America·G BarbaC Bréchot
Sep 26, 1997·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·J H Hoofnagle
Jun 17, 1998·Journal of Virology·K YasuiM Kohara
Jul 11, 1998·Journal of Virology·S I Schmid, P Hearing
Mar 3, 1999·Proceedings of the National Academy of Sciences of the United States of America·M YanagiJ Bukh
Dec 11, 1999·Current Topics in Microbiology and Immunology·N Kato, K Shimotohno

❮ Previous
Next ❯

Citations

May 8, 2003·Journal of Biosciences·Nicole Pavio, Michael M C Lai
May 8, 2003·Journal of Biosciences·G Waris, A Siddiqui
Apr 12, 2012·Archives of Virology·Chao ChenRong-Ge Yang
Mar 3, 2007·Digestive Diseases and Sciences·Gary L DavisGyongyi Szabo
Nov 26, 2003·Antiviral Research·Ralf BartenschlagerSandra Sparacio
Mar 16, 2005·Biochemical and Biophysical Research Communications·Masanori IkedaNobuyuki Kato
Jun 21, 2005·Journal of Hepatology·Ralf Bartenschlager
May 26, 2004·Journal of Virological Methods·Laurence CagnonKenneth A Simmen
Jun 18, 2003·Biochemical and Biophysical Research Communications·Nobuyuki KatoKunitada Shimotohno
Sep 3, 2003·Virus Research·Adrish SenRatna B Ray
Oct 26, 2002·Journal of Hepatology·Xavier FornsRobert H Purcell
May 29, 2003·Biochimie·Anne Goffard, Jean Dubuisson
Nov 26, 2002·Trends in Cell Biology·Jean DubuissonDarius Moradpour
Aug 6, 2002·Current Opinion in Microbiology·Timothy L Tellinghuisen, Charles M Rice
Sep 27, 2002·Current Opinion in Pharmacology·Hengli TangFlossie Wong-Staal
Oct 18, 2002·Trends in Molecular Medicine·Darius MoradpourHubert E Blum
Mar 16, 2004·Clinical Gastroenterology and Hepatology : the Official Clinical Practice Journal of the American Gastroenterological Association·David A Brenner
Jul 19, 2011·Journal of Medicinal Chemistry·Rui LiuGang Liu
May 18, 2005·Oncogene·Naoual L Benali-FuretPatrizia Paterlini-Bréchot
Nov 26, 2002·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Hideki AizakiTetsuro Suzuki
Aug 25, 2004·Proceedings of the National Academy of Sciences of the United States of America·Matthew J EvansStephen P Goff
Nov 9, 2010·The Journal of Biological Chemistry·Andreas MerzRalf Bartenschlager
Mar 5, 2003·The Journal of Experimental Medicine·Birke BartoschFrançois-Loïc Cosset
Feb 13, 2003·Nucleic Acids Research·Estelle DumasMichel Ventura
Nov 28, 2007·Antimicrobial Agents and Chemotherapy·Yingjia ZhangWeidong Hao
Apr 11, 2007·Antimicrobial Agents and Chemotherapy·Masahiko YanoNobuyuki Kato
Jan 27, 2004·Antimicrobial Agents and Chemotherapy·Lieven J StuyverMichael J Otto
Apr 12, 2012·Journal of Virology·Peter D BurbeloAmit Kapoor
Jul 29, 2006·Journal of Virology·Bon Chang A KooStephen J Polyak
May 25, 2007·Journal of Virology·Timothy L TellinghuisenCharles M Rice
Aug 17, 2012·Journal of Virology·Daniel Da CostaThomas F Baumert

❮ Previous
Next ❯

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.