Next Article in Journal
The Standard Scrapie Cell Assay: Development, Utility and Prospects
Previous Article in Journal
Molecular Biology of KSHV Lytic Reactivation
Article Menu

Export Article

Open AccessArticle
Viruses 2015, 7(1), 154-179; doi:10.3390/v7010154

Cell Penetrable Human scFv Specific to Middle Domain of Matrix Protein-1 Protects Mice from Lethal Influenza

1
Center for Agricultural Biotechnology, Kasetsart University, Kamphaeng Saen Campus, Nakhon Pathom 73140, Thailand
2
Laboratory for Research and Technology Development, Department of Parasitology, and Center of Excellence on Therapeutic Proteins and Antibody Engineering, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
3
Department of Veterinary Pathology, Faculty of Veterinary Medicine, Kasetsart University, Kamphaeng Saen Campus, Nakhon Pathom 73140, Thailand
4
Chulabhorn International College of Medicine, Thammasat University, Pathumthani 12120, Thailand
5
Graduate Program in Biomedical Science, Faculty of Allied Health Sciences, Thammasat University, Pathumthani 12120, Thailand
6
Department of Microbiology and Immunology, Faculty of Veterinary Medicine, Kasetsart University, Bangkok 10900, Thailand
*
Author to whom correspondence should be addressed.
Academic Editor: Curt Hagedorn
Received: 20 September 2014 / Accepted: 5 January 2015 / Published: 14 January 2015
(This article belongs to the Section Antivirals & Vaccines)
View Full-Text   |   Download PDF [2920 KB, uploaded 12 May 2015]   |  

Abstract

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. View Full-Text
Keywords: Cell penetrating antibody; H5N1; human ScFv; influenza; influenza virus; matrix protein-1 (M1); middle domain of M1; molecular docking; phage display; transbody Cell penetrating antibody; H5N1; human ScFv; influenza; influenza virus; matrix protein-1 (M1); middle domain of M1; molecular docking; phage display; transbody
Figures

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Dong-din-on, F.; Songserm, T.; Pissawong, T.; Srimanote, P.; Thanongsaksrikul, J.; Thueng-in, K.; Moonjit, P.; Lertwatcharasarakul, P.; Seesuay, W.; Chaicumpa, W. Cell Penetrable Human scFv Specific to Middle Domain of Matrix Protein-1 Protects Mice from Lethal Influenza. Viruses 2015, 7, 154-179.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Viruses EISSN 1999-4915 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top