Impaired antiviral activity of interferon alpha against hepatitis C virus 2a in Huh-7 cells with a defective Jak-Stat pathway
Authors: Partha K Chandra
Gus Kousoulas
Bret Poat
Sidhartha Hazari
Robert F Garry
Sibnarayan Datta
Timothy P Foster
Takaji Wakita
Srikanta Dash
Journal: Virology Journal (2010)
Discipline: MICROBIOLOGY
Keywords: IFN-alpha; HCV genotype; Jak-Stat pathway; replication system; GFP
Affiliations: Department of Pathology and Laboratory Medicine, Tulane University of Health Sciences Center, 1430 Tulane Ave, New Orleans, LA 70112, USA.

Abstract:  Background: The sustained virological response to interferon-alpha (IFN-alpha) in individuals infected with hepatitis C virus (HCV) genotype 1 is only 50%, but is about 80% in patients infected with genotype 2-6 viruses. The molecular mechanisms explaining the differences in IFN-alpha responsiveness between HCV 1 and other genotypes have not been elucidated. Results: Virus and host cellular factors contributing to IFN responsiveness were analyzed using a green fluorescence protein (GFP) based replication system of HCV 2a and Huh-7 cell clones that either possesses or lack a functional Jak-Stat pathway. The GFP gene was inserted into the C-terminal non-structural protein 5A of HCV 2a full-length and sub-genomic clones. Both HCV clones replicated to a high level in Huh-7 cells and could be visualized by either fluorescence microscopy or flow cytometric analysis. Huh-7 cells transfected with the GFP tagged HCV 2a genome produced infectious virus particles and the replication of fluorescence virus particles was demonstrated in na√Øve Huh-7.5 cells after infection. IFN-alpha effectively inhibited the replication of full-length as well as sub-genomic HCV 2a clones in Huh-7 cells with a functional Jak-Stat pathway. However, the antiviral effect of IFN-alpha against HCV 2a virus was not observed in Huh-7 cell clones with a defect in Jak-Stat signaling. HCV infection or replication did not alter IFN-alpha induced Stat phosphorylation or ISRE promoter-luciferase activity in both the sensitive and resistant Huh-7 cell clones. Conclusions: The cellular Jak-Stat pathway is critical for a successful IFN-alpha antiviral response against HCV 2a. HCV infection or replication did not alter signaling by the Jak-Stat pathway. GFP labeled JFH1 2a replicon based stable cell lines with IFN sensitive and IFN resistant phenotypes can be used to develop new strategies to overcome IFN-resistance against hepatitis C. 

Retracted: No

PubPeer comments:
 Brought to my attention by a reader. This paper, describing graphene-WS2 structures, looks remarkably similar to another paper by the same researchers, describing graphene-MoS2 structures. That paper is: Ashkan Horri et al., IEEE Transactions on Electron Devices (2017), DOI: 10.1109 TED.2017.2716938 - https: pubpeer.com publications 1B8B32C49228874857C6D944F9A242 Both papers were submitted to the journals on the same day, 21 January 2017. In the comparisons below, I will call this paper  IEEE-TED 2017 [*right*], and the other paper  JAP 2017 [*left*]. Here are the two titles and abstracts.  Here are the texts of the two papers (lightly edited to remove formulas) compared to each other with SimTexter . The highlighted words are verbatim matches.  Here are Figures 1 and Figures 2 compared.  Several other figures look very similar between the two papers but I am not sure if those are expected or unexpected similarities. ,