Publication: Human transbodies to VP40 inhibit cellular egress of Ebola virus-like particles
Issued Date
2016-10-14
Resource Type
ISSN
10902104
0006291X
0006291X
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2-s2.0-84989184678
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Mahidol University
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SCOPUS
Bibliographic Citation
Biochemical and Biophysical Research Communications. Vol.479, No.2 (2016), 245-252
Suggested Citation
Salma Teimoori, Watee Seesuay, Surasak Jittavisutthikul, Urai Chaisri, Nitat Sookrung, Jaslan Densumite, Nawannaporn Saelim, Monrat Chulanetra, Santi Maneewatch, Wanpen Chaicumpa Human transbodies to VP40 inhibit cellular egress of Ebola virus-like particles. Biochemical and Biophysical Research Communications. Vol.479, No.2 (2016), 245-252. doi:10.1016/j.bbrc.2016.09.052 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/42924
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Title
Human transbodies to VP40 inhibit cellular egress of Ebola virus-like particles
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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.