Cell penetrable human scFv specific to middle domain of matrix protein-1 protects mice from lethal influenza

dc.contributor.authorFonthip Dong-Din-Onen_US
dc.contributor.authorThaweesak Songsermen_US
dc.contributor.authorTippawan Pissawongen_US
dc.contributor.authorPotjanee Srimanoteen_US
dc.contributor.authorJeeraphong Thanongsaksrikulen_US
dc.contributor.authorKanyarat Thueng-Inen_US
dc.contributor.authorPattra Moonjiten_US
dc.contributor.authorPreeda Lertwatcharasarakulen_US
dc.contributor.authorWatee Seesuayen_US
dc.contributor.authorWanpen Chaicumpaen_US
dc.contributor.otherKasetsart Universityen_US
dc.contributor.otherMahidol Universityen_US
dc.contributor.otherThammasat Universityen_US
dc.description.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.en_US
dc.identifier.citationViruses. Vol.7, No.1 (2015), 154-179en_US
dc.rightsMahidol Universityen_US
dc.subjectImmunology and Microbiologyen_US
dc.titleCell penetrable human scFv specific to middle domain of matrix protein-1 protects mice from lethal influenzaen_US