Simple jQuery Dropdowns
Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/40767
Title: Human transbodies to HCV NS3/4A protease inhibit viral replication and restore host innate immunity
Authors: Surasak Jittavisutthikul
Watee Seesuay
Jeeraphong Thanongsaksrikul
Kanyarat Thueng-in
Potjanee Srimanote
Rolf G. Werner
Wanpen Chaicumpa
Mahidol University
Thammasat University
Suranaree University of Technology
Universität Tübingen
Keywords: Immunology and Microbiology;Medicine
Issue Date: 26-Aug-2016
Citation: Frontiers in Immunology. Vol.7, No.AUG (2016)
Abstract: © 2016 Jittavisutthikul, Seesuay, Thanongsaksrikul, Thueng-in, Srimanote, Werner and Chaicumpa. A safe and effective direct acting anti-hepatitis C virus (HCV) agent is still needed. In this study, human single chain variable fragments of antibody (scFvs) that bound to HCV NS3/4A protein were produced by phage display technology. The engineered scFvs were linked to nonaarginines (R9) for making them cell penetrable. HCV-RNA-transfected Huh7 cells treated with the transbodies produced from four different transformed E. coli clones had reduced HCV-RNA inside the cells and in the cell spent media, as well as fewer HCV foci in the cell monolayer compared to the transfected cells in culture medium alone. The transbodies-treated transfected cells also had up-expression of the genes coding for the host innate immune response, including TRIF, TRAF3, IRF3, IL-28B, and IFN-β. Computerized homology modeling and intermolecular docking predicted that the effective transbodies interacted with several critical residues of the NS3/4A protease, including those that form catalytic triads, oxyanion loop, and S1 and S6 pockets, as well as a zinc-binding site. Although insight into molecular mechanisms of the transbodies need further laboratory investigation, it can be deduced from the current data that the transbodies blocked the HCV NS3/4A protease activities, leading to the HCV replication inhibition and restoration of the virally suppressed host innate immunity. The engineered antibodies should be tested further for treatment of HCV infection either alone, in combination with current therapeutics, or in a mixture with their cognates specific to other HCV proteins.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84989345389&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/40767
ISSN: 16643224
Appears in Collections:Scopus 2016-2017

Files in This Item:
There are no files associated with this item.


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.