Publication: Inhibition of HCV replication by humanized-single domain transbodies to NS4B
4
Issued Date
2016-08-05
Resource Type
ISSN
10902104
0006291X
0006291X
Other identifier(s)
2-s2.0-84971645642
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Mahidol University
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SCOPUS
Bibliographic Citation
Biochemical and Biophysical Research Communications. Vol.476, No.4 (2016), 654-664
Suggested Citation
Kittirat Glab-ampai, Aijaz Ahmad Malik, Monrat Chulanetra, Jeeraphong Thanongsaksrikul, Kanyarat Thueng-in, Potjanee Srimanote, Pongsri Tongtawe, Wanpen Chaicumpa Inhibition of HCV replication by humanized-single domain transbodies to NS4B. Biochemical and Biophysical Research Communications. Vol.476, No.4 (2016), 654-664. doi:10.1016/j.bbrc.2016.05.109 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/42917
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Title
Inhibition of HCV replication by humanized-single domain transbodies to NS4B
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Abstract
© 2016 Elsevier Inc. NS4B of hepatitis C virus (HCV) initiates membrane web formation, binds RNA and other HCV proteins for viral replication complex (RC) formation, hydrolyses NTP, and inhibits innate anti-viral immunity. Thus, NS4B is an attractive target of a novel anti-HCV agent. In this study, humanized-nanobodies (VHs/VHHs) that bound to recombinant NS4B were produced by means of phage display technology. The nanobodies were linked molecularly to a cell penetrating peptide, penetratin (PEN), for making them cell penetrable (become transbodies). Human hepatic (Huh7) cells transfected with HCV JFH1-RNA that were treated with transbodies from four Escherichia coli clones (PEN-VHH7, PEN-VHH9, PEN-VH33, and PEN-VH43) had significant reduction of HCV RNA amounts in their culture fluids and intracellularly when compared to the transfected cells treated with control transbody and medium alone. The results were supported by the HCV foci assay. The transbody treated-transfected cells also had upregulation of the studied innate cytokine genes, IRF3, IFNβ and IL-28b. The transbodies have high potential for testing further as a novel anti-HCV agent, either alone, adjunct of existing anti-HCV agents/remedies, or in combination with their cognates specific to other HCV enzymes/proteins.