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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/36128
Title: Cell penetrable human scFv specific to middle domain of matrix protein-1 protects mice from lethal influenza
Authors: Fonthip Dong-Din-On
Thaweesak Songserm
Tippawan Pissawong
Potjanee Srimanote
Jeeraphong Thanongsaksrikul
Kanyarat Thueng-In
Pattra Moonjit
Preeda Lertwatcharasarakul
Watee Seesuay
Wanpen Chaicumpa
Kasetsart University
Mahidol University
Thammasat University
Keywords: Immunology and Microbiology;Medicine
Issue Date: 14-Jan-2015
Citation: Viruses. Vol.7, No.1 (2015), 154-179
Abstract: © 2015 by the authors; licensee MDPI, Basel, Switzerland. A new anti-influenza remedy that can tolerate the virus antigenic variation is needed. Influenza virus matrix protein-1 (M1) is highly conserved and pivotal for the virus replication cycle: virus uncoating, assembly and budding. An agent that blocks the M1 functions should be an effective anti-influenza agent. In this study, human scFv that bound to recombinant M1 middle domain (MD) and native M1 of A/H5N1 was produced. Phage mimotope search and computerized molecular docking revealed that the scFv bound to the MD conformational epitope formed by juxtaposed helices 7 and 9 of the M1. The scFv was linked molecularly to a cell penetrable peptide, penetratin (PEN). The PEN-scFv (transbody), when used to treat the cells pre-infected with the heterologous clade/subclade A/H5N1 reduced the viral mRNA intracellularly and in the cell culture fluids. The transbody mitigated symptom severity and lung histopathology of the H5N1 infected mice and caused reduction of virus antigen in the tissues as well as extricated the animals from the lethal challenge in a dose dependent manner. The transbody specific to the M1 MD, either alone or in combination with the cognate human scFvs specific to other influenza virus proteins, should be an effective, safe and mutation tolerable anti-influenza agent.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84921473751&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/36128
ISSN: 19994915
Appears in Collections:Scopus 2011-2015

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