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Title: Foot-and-Mouth Disease (FMD) Virus 3C Protease Mutant L127P: Implications for FMD Vaccine Development

Journal Article · · Journal of Virology
 [1];  [2];  [2];  [3];  [4];  [3];  [3];  [5];  [4];  [3];  [5];  [5]
  1. 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; DOE/OSTI
  2. 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
  3. Leidos, Inc., Greenport, NY (United States). Plum Island Animal Disease Center
  4. Oak Ridge Inst. for Science and Education (ORISE), Oak Ridge, TN (United States). Plum Island Animal Disease Center Research Participation Program
  5. US Dept. of Homeland Security (DHS), Greenport, NY (United States). Plum Island Animal Disease Center
+ Show Author Affiliations

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.

Research Organization:
Oak Ridge Associated Univ., Oak Ridge, TN (United States)
Sponsoring Organization:
USDOE
Grant/Contract Number:
AC05-06OR23100
OSTI ID:
1626072
Journal Information:
Journal of Virology, Journal Name: Journal of Virology Journal Issue: 22 Vol. 91; ISSN 0022-538X
Publisher:
American Society for MicrobiologyCopyright Statement
Country of Publication:
United States
Language:
English

References (64)

Efficient production of foot-and-mouth disease virus empty capsids in insect cells following down regulation of 3C protease activity journal February 2013
Genetic heterogeneity in the foot-and-mouth disease virus Leader and 3C proteinases journal May 2002
Evaluation of Gaussia luciferase and foot-and-mouth disease virus 2A translational interrupter chimeras as polycistronic reporters for transgene expression journal June 2017
Cleavage of translation initiation factor 4AI (eIF4AI) but not eIF4AII by foot-and-mouth disease virus 3C protease: identification of the eIF4AI cleavage site journal October 2001
Sequential modification of translation initiation factor eIF4GI by two different foot-and-mouth disease virus proteases within infected baby hamster kidney cells: identification of the 3Cpro cleavage site journal October 2004
pAd5-Blue: Direct Ligation System for Engineering Recombinant Adenovirus Constructs journal November 2001
Crystal Structure of Foot-and-Mouth Disease Virus 3C Protease: NEW INSIGHTS INTO CATALYTIC MECHANISM AND CLEAVAGE SPECIFICITY journal January 2005
Development of transgenic alfalfa plants containing the foot and mouth disease virus structural polyprotein gene P1 and its utilization as an experimental immunogen journal March 2005
Characterization of the Foot-and-Mouth Disease Virus 3C Protease Expressed in Escherichia coli journal November 1993
Multiple efficacy studies of an adenovirus-vectored foot-and-mouth disease virus serotype A24 subunit vaccine in cattle using homologous challenge journal June 2016
Production and characterization of two serotype independent monoclonal antibodies against foot-and-mouth disease virus journal January 2007
Biologically active protease of foot and mouth disease virus is expressed from cloned viral cDNA in Escherichia coli. journal June 1984
Crystallization of foot-and-mouth disease virus 3C protease: surface mutagenesis and a novel crystal-optimization strategy journal April 2005
Electron microscopic observation of crystalline arrays of foot-and-mouth disease virus. journal January 1966
Structural and Mutagenic Analysis of Foot-and-Mouth Disease Virus 3C Protease Reveals the Role of the β-Ribbon in Proteolysis journal October 2006
Foot-and-Mouth Disease Virus 3C Protease Induces Cleavage of Translation Initiation Factors eIF4A and eIF4G within Infected Cells journal January 2000
Multiple efficacy studies of an adenovirus-vectored foot-and-mouth disease virus serotype A24 subunit vaccine in cattle using homologous challenge journal June 2016
Analysis of Foot-and-Mouth Disease Virus Type O1 Brugge Neutralization Epitopes Using Monoclonal Antibodies journal October 1986
Sequential modification of translation initiation factor eIF4GI by two different foot-and-mouth disease virus proteases within infected baby hamster kidney cells: identification of the 3Cpro cleavage site journal December 2004
Immune responses and protection against foot-and-mouth disease virus (FMDV) challenge in swine vaccinated with adenovirus-FMDV constructs journal February 2001
Early protection against homologous challenge after a single dose of replication-defective human adenovirus type 5 expressing capsid proteins of foot-and-mouth disease virus (FMDV) strain A24 journal February 2002
Rapid protection of cattle from direct challenge with foot-and-mouth disease virus (FMDV) by a single inoculation with an adenovirus-vectored FMDV subunit vaccine journal July 2005
The nuclear protein Sam68 is cleaved by the FMDV 3C protease redistributing Sam68 to the cytoplasm during FMDV infection of host cells journal March 2012
Delivery of a foot-and-mouth disease virus empty capsid subunit antigen with nonstructural protein 2B improves protection of swine journal October 2008
Biologically active protease of foot and mouth disease virus is expressed from cloned viral cDNA in Escherichia coli. journal June 1984
pAd5-Blue: Direct Ligation System for Engineering Recombinant Adenovirus Constructs journal November 2001
Capsid intermediates assembled in a foot-and-mouth disease virus genome RNA-programmed cell-free translation system and in infected cells. journal January 1985
Rapid protection of cattle from direct challenge with foot-and-mouth disease virus (FMDV) by a single inoculation with an adenovirus-vectored FMDV subunit vaccine journal July 2005
Foot-and-Mouth Disease Virus 3C Protease Cleaves NEMO To Impair Innate Immune Signaling journal June 2012
Delivery of a foot-and-mouth disease virus empty capsid subunit antigen with nonstructural protein 2B improves protection of swine journal October 2008
Sequential modification of translation initiation factor eIF4GI by two different foot-and-mouth disease virus proteases within infected baby hamster kidney cells: identification of the 3Cpro cleavage site journal December 2004
The economic impacts of foot and mouth disease – What are they, how big are they and where do they occur? journal November 2013
Foot-and-mouth disease virus protease 3C induces specific proteolytic cleavage of host cell histone H3. journal January 1990
Antigenic comparison of different foot-and-mouth disease vims types using monoclonal antibodies defining multiple neutralizing epitopes on FMDV A5 subtypes journal May 1989
Assembly and characterization of foot-and-mouth disease virus empty capsid particles expressed within mammalian cells journal August 2013
Evaluation of Gaussia luciferase and foot-and-mouth disease virus 2A translational interrupter chimeras as polycistronic reporters for transgene expression journal June 2017
Insights into Cleavage Specificity from the Crystal Structure of Foot-and-Mouth Disease Virus 3C Protease Complexed with a Peptide Substrate journal January 2010
Early protection against homologous challenge after a single dose of replication-defective human adenovirus type 5 expressing capsid proteins of foot-and-mouth disease virus (FMDV) strain A24 journal February 2002
Production and characterization of two serotype independent monoclonal antibodies against foot-and-mouth disease virus journal January 2007
Electron microscopic observation of crystalline arrays of foot-and-mouth disease virus. journal January 1966
Development of Replication-Defective Adenovirus Serotype 5 Containing the Capsid and 3C Protease Coding Regions of Foot-and-Mouth Disease Virus as a Vaccine Candidate journal October 1999
Immune responses and protection against foot-and-mouth disease virus (FMDV) challenge in swine vaccinated with adenovirus-FMDV constructs journal February 2001
Characterization of the Foot-and-Mouth Disease Virus 3C Protease Expressed in Escherichia coli journal November 1993
Crystallization of foot-and-mouth disease virus 3C protease: surface mutagenesis and a novel crystal-optimization strategy journal April 2005
The economic impacts of foot and mouth disease – What are they, how big are they and where do they occur? journal November 2013
Cleavage of translation initiation factor 4AI (eIF4AI) but not eIF4AII by foot-and-mouth disease virus 3C protease: identification of the eIF4AI cleavage site journal October 2001
Foot-and-mouth disease virus protease 3C induces specific proteolytic cleavage of host cell histone H3. journal January 1990
Development of Replication-Defective Adenovirus Serotype 5 Containing the Capsid and 3C Protease Coding Regions of Foot-and-Mouth Disease Virus as a Vaccine Candidate journal October 1999
Identification of the Active-Site Residues of the 3C Proteinase of Foot-and-Mouth Disease Virus journal November 1995
Foot-and-Mouth Disease Virus 3C Protease Induces Fragmentation of the Golgi Compartment and Blocks Intra-Golgi Transport journal August 2013
FMD vaccines journal January 2003
Foot-and-mouth disease virus protease 3C induces specific proteolytic cleavage of host cell histone H3. journal January 1990
Antigenic comparison of different foot-and-mouth disease vims types using monoclonal antibodies defining multiple neutralizing epitopes on FMDV A5 subtypes journal May 1989
Electron microscopic observation of crystalline arrays of foot-and-mouth disease virus. journal January 1966
Evaluation of a Fiber-Modified Adenovirus Vector Vaccine against Foot-and-Mouth Disease in Cattle journal November 2015
Development of transgenic alfalfa plants containing the foot and mouth disease virus structural polyprotein gene P1 and its utilization as an experimental immunogen journal March 2005
Capsid intermediates assembled in a foot-and-mouth disease virus genome RNA-programmed cell-free translation system and in infected cells. journal January 1985
Genetic heterogeneity in the foot-and-mouth disease virus Leader and 3C proteinases journal May 2002
Foot-and-Mouth Disease Virus 3C Protease Induces Fragmentation of the Golgi Compartment and Blocks Intra-Golgi Transport journal August 2013
Assembly and characterization of foot-and-mouth disease virus empty capsid particles expressed within mammalian cells journal August 2013
FMD vaccines journal January 2003
Insights into Cleavage Specificity from the Crystal Structure of Foot-and-Mouth Disease Virus 3C Protease Complexed with a Peptide Substrate journal January 2010
Efficient production of foot-and-mouth disease virus empty capsids in insect cells following down regulation of 3C protease activity journal February 2013
The nuclear protein Sam68 is cleaved by the FMDV 3C protease redistributing Sam68 to the cytoplasm during FMDV infection of host cells journal March 2012

Cited By (3)

Review on Outbreak Dynamics, the Endemic Serotypes, and Diversified Topotypic Profiles of Foot and Mouth Disease Virus Isolates in Ethiopia from 2008 to 2018 journal November 2019
Early IgG Response to Foot and Mouth Disease Vaccine Formulated with a Vegetable Oil Adjuvant journal October 2019
Early IgG Response to Foot and Mouth Disease Vaccine Formulated with a Vegetable Oil Adjuvant journal October 2019

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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