Foot-and-Mouth Disease (FMD) Virus 3C Protease Mutant L127P: Implications for FMD Vaccine Development
Abstract
ABSTRACT The foot-and-mouth disease virus (FMDV) afflicts livestock in more than 80 countries, limiting food production and global trade. Production of foot-and-mouth disease (FMD) vaccines requires cytosolic expression of the FMDV 3C protease to cleave the P1 polyprotein into mature capsid proteins, but the FMDV 3C protease is toxic to host cells. To identify less-toxic isoforms of the FMDV 3C protease, we screened 3C mutants for increased transgene output in comparison to wild-type 3C using aGaussialuciferase reporter system. The novel point mutation 3C(L127P) increased yields of recombinant FMDV subunit proteins in mammalian and bacterial cells expressing P1-3C transgenes and retained the ability to process P1 polyproteins from multiple FMDV serotypes. The 3C(L127P) mutant produced crystalline arrays of FMDV-like particles in mammalian and bacterial cells, potentially providing a practical method of rapid, inexpensive FMD vaccine production in bacteria. IMPORTANCEThe mutant FMDV 3C protease L127P significantly increased yields of recombinant FMDV subunit antigens and produced virus-like particles in mammalian and bacterial cells. The L127P mutation represents a novel advancement for economical FMD vaccine production.
- Authors:
-
- US Dept. of Homeland Security (DHS), Greenport, NY (United States). Plum Island Animal Disease Center; Leidos, Inc., Greenport, NY (United States). Plum Island Animal Disease Center; Oak Ridge Inst. for Science and Education (ORISE), Oak Ridge, TN (United States). Plum Island Animal Disease Center Research Participation Program
- Leidos, Inc., Greenport, NY (United States). Plum Island Animal Disease Center; Oak Ridge Inst. for Science and Education (ORISE), Oak Ridge, TN (United States). Plum Island Animal Disease Center Research Participation Program
- Leidos, Inc., Greenport, NY (United States). Plum Island Animal Disease Center
- Oak Ridge Inst. for Science and Education (ORISE), Oak Ridge, TN (United States). Plum Island Animal Disease Center Research Participation Program
- US Dept. of Homeland Security (DHS), Greenport, NY (United States). Plum Island Animal Disease Center;
- Leidos, Inc., Greenport, NY (United States). Plum Island Animal Disease Center;
- Publication Date:
- Research Org.:
- Oak Ridge Associated Univ., Oak Ridge, TN (United States)
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1626072
- Grant/Contract Number:
- AC05-06OR23100; HSHQDC-14-F-00035; HSHQPM-14-X00001
- Resource Type:
- Journal Article: Accepted Manuscript
- Journal Name:
- Journal of Virology
- Additional Journal Information:
- Journal Volume: 91; Journal Issue: 22; Journal ID: ISSN 0022-538X
- Publisher:
- American Society for Microbiology
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; Virology; 3C protease; StopGo translation; Escherichia coli; Gaussia luciferase; VLP; adenoviruses; foot-and-mouth disease virus; in vivo; in vivo expression technology; translational interrupter; vaccines; virus-like particles
Citation Formats
Puckette, Michael, Clark, Benjamin A., Smith, Justin D., Turecek, Traci, Martel, Erica, Gabbert, Lindsay, Pisano, Melia, Hurtle, William, Pacheco, Juan M., Barrera, José, Neilan, John G., and Rasmussen, Max. Foot-and-Mouth Disease (FMD) Virus 3C Protease Mutant L127P: Implications for FMD Vaccine Development. United States: N. p., 2017.
Web. doi:10.1128/jvi.00924-17.
Puckette, Michael, Clark, Benjamin A., Smith, Justin D., Turecek, Traci, Martel, Erica, Gabbert, Lindsay, Pisano, Melia, Hurtle, William, Pacheco, Juan M., Barrera, José, Neilan, John G., & Rasmussen, Max. Foot-and-Mouth Disease (FMD) Virus 3C Protease Mutant L127P: Implications for FMD Vaccine Development. United States. https://doi.org/10.1128/jvi.00924-17
Puckette, Michael, Clark, Benjamin A., Smith, Justin D., Turecek, Traci, Martel, Erica, Gabbert, Lindsay, Pisano, Melia, Hurtle, William, Pacheco, Juan M., Barrera, José, Neilan, John G., and Rasmussen, Max. Wed .
"Foot-and-Mouth Disease (FMD) Virus 3C Protease Mutant L127P: Implications for FMD Vaccine Development". United States. https://doi.org/10.1128/jvi.00924-17. https://www.osti.gov/servlets/purl/1626072.
@article{osti_1626072,
title = {Foot-and-Mouth Disease (FMD) Virus 3C Protease Mutant L127P: Implications for FMD Vaccine Development},
author = {Puckette, Michael and Clark, Benjamin A. and Smith, Justin D. and Turecek, Traci and Martel, Erica and Gabbert, Lindsay and Pisano, Melia and Hurtle, William and Pacheco, Juan M. and Barrera, José and Neilan, John G. and Rasmussen, Max},
abstractNote = {ABSTRACT The foot-and-mouth disease virus (FMDV) afflicts livestock in more than 80 countries, limiting food production and global trade. Production of foot-and-mouth disease (FMD) vaccines requires cytosolic expression of the FMDV 3C protease to cleave the P1 polyprotein into mature capsid proteins, but the FMDV 3C protease is toxic to host cells. To identify less-toxic isoforms of the FMDV 3C protease, we screened 3C mutants for increased transgene output in comparison to wild-type 3C using aGaussialuciferase reporter system. The novel point mutation 3C(L127P) increased yields of recombinant FMDV subunit proteins in mammalian and bacterial cells expressing P1-3C transgenes and retained the ability to process P1 polyproteins from multiple FMDV serotypes. The 3C(L127P) mutant produced crystalline arrays of FMDV-like particles in mammalian and bacterial cells, potentially providing a practical method of rapid, inexpensive FMD vaccine production in bacteria. IMPORTANCEThe mutant FMDV 3C protease L127P significantly increased yields of recombinant FMDV subunit antigens and produced virus-like particles in mammalian and bacterial cells. The L127P mutation represents a novel advancement for economical FMD vaccine production.},
doi = {10.1128/jvi.00924-17},
url = {https://www.osti.gov/biblio/1626072},
journal = {Journal of Virology},
issn = {0022-538X},
number = 22,
volume = 91,
place = {United States},
year = {2017},
month = {9}
}
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Works referencing / citing this record:
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