Dominant negative effect of wild-type NS5A on NS5A-adapted subgenomic hepatitis C virus RNA replicon

The Journal of General Virology
Rita Graziani, Giacomo Paonessa

Abstract

An efficient model is currently used to study hepatitis C virus (HCV) replication in cell culture. It involves transfection in Huh7, a hepatoma-derived cell line, of an antibiotic (neomycin) selectable HCV subgenomic replicon encoding the non-structural (NS) proteins from NS3 to NS5B. However, strong and sustained replication is achieved only on the appearance of adaptive mutations in viral proteins. The most effective of these adaptive mutations are concentrated mainly in NS5A, not only into the original Con1 but also in the recently established HCV-BK and HCV-H77 isolate-derived replicons. This suggests that the expression of wild-type (wt) NS5A may not allow efficient HCV RNA replication in cell culture. With the use of a beta-lactamase reporter gene as a marker for HCV replication and TaqMan RNA analysis, the replication of different HCV replicons in cotransfection experiments was investigated. Comparing wt with NS5A-adapted replicons, the strong evidence accumulated showed that the expression of wt NS5A was actually able to inhibit the replication of NS5A-adapted replicons. This feature was characterized as a dominant negative effect. Interestingly, an NS5B (R2884G)-adapted replicon, containing a wt NS5A, was dominant nega...Continue Reading

References

Feb 1, 1997·Kansenshōgaku zasshi. The Journal of the Japanese Association for Infectious Diseases·I MiyajimaK Tanikawa
Feb 25, 1999·Gastroenterology·T TakeuchiM Kohara
Jul 13, 2000·Baillière's Best Practice & Research. Clinical Gastroenterology·G R Foster, H C Thomas
Dec 9, 2000·Science·K J BlightC M Rice
Jan 11, 2001·Journal of Virology·V LohmannR Bartenschlager
Apr 20, 2001·Journal of Virology·N KriegerR Bartenschlager
Aug 17, 2001·Journal of Virology·J T GuoC Seeger
Sep 1, 2001·Antiviral Research·R Bartenschlager, V Lohmann
Jul 9, 2002·Oncogene·Keng-Hsin LanShou-Dong Lee
Oct 23, 2002·Proceedings of the National Academy of Sciences of the United States of America·Jens BukhRalf Bartenschlager
Nov 20, 2002·Journal of Virology·Keril J BlightCharles M Rice
Feb 14, 2003·Journal of Virology·Keril J BlightCharles M Rice
Mar 5, 2003·The Journal of Biological Chemistry·Jay A GroblerOsvaldo A Flores
Apr 15, 2003·Clinics in Liver Disease·Raffaele De Francesco, Charles M Rice

❮ Previous
Next ❯

Citations

Nov 5, 2014·ELife·Elizabeth J TannerKarla Kirkegaard
Sep 9, 2005·Virus Research·Xiao Tong, Bruce A Malcolm
Apr 8, 2015·Virology·Maria Teresa Catanese, Marcus Dorner
Oct 21, 2016·Current Opinion in Virology·Karla KirkegaardRoberto Mateo
Mar 29, 2018·ELife·Nicholas van BuurenKarla Kirkegaard

❮ Previous
Next ❯

Related Concepts

Related Feeds

Aminoglycosides (ASM)

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Aminoglycosides

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.