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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/42924
Title: Human transbodies to VP40 inhibit cellular egress of Ebola virus-like particles
Authors: Salma Teimoori
Watee Seesuay
Surasak Jittavisutthikul
Urai Chaisri
Nitat Sookrung
Jaslan Densumite
Nawannaporn Saelim
Monrat Chulanetra
Santi Maneewatch
Wanpen Chaicumpa
Mahidol University
Keywords: Biochemistry, Genetics and Molecular Biology
Issue Date: 14-Oct-2016
Citation: Biochemical and Biophysical Research Communications. Vol.479, No.2 (2016), 245-252
Abstract: © 2016 Elsevier Inc. A direct acting anti-Ebola agent is needed. VP40, a conserved protein across Ebolavirus (EBOV) species has several pivotal roles in the virus life cycle. Inhibition of VP40 functions would lessen the virion integrity and interfere with the viral assembly, budding, and spread. In this study, cell penetrable human scFvs (HuscFvs) that bound to EBOV VP40 were produced by phage display technology. Gene sequences coding for VP40-bound-HuscFvs were subcloned from phagemids into protein expression plasmids downstream to a gene of cell penetrating peptide, i.e., nonaarginine (R9). By electron microscopy, transbodies from three clones effectively inhibited egress of the Ebola virus-like particles from human hepatic cells transduced with pseudo-typed-Lentivirus particles carrying EBOV VP40 and GP genes. Computerized simulation indicated that the effective HuscFvs bound to multiple basic residues in the cationic patch of VP40 C-terminal domain which are important in membrane-binding for viral matrix assembly and virus budding. The transbodies bound also to VP40 N-terminal domain and L domain peptide encompassed the PTAPPEY (WW binding) motif, suggesting that they might confer VP40 function inhibition through additional mechanism(s). The generated transbodies are worthwhile tested with authentic EBOV before developing to direct acting anti-Ebola agent for preclinical and clinical trials.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84989184678&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/42924
ISSN: 10902104
0006291X
Appears in Collections:Scopus 2016-2017

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