A mutant of Asia 1 serotype of Foot-and-mouth disease virus with the deletion of an important antigenic epitope in the 3A protein

2011 ◽  
Vol 57 (3) ◽  
pp. 169-176 ◽  
Author(s):  
Shuang Li ◽  
Mingchun Gao ◽  
Runxiang Zhang ◽  
Ge Song ◽  
Jun Song ◽  
...  
Keyword(s):  
Disease Virus ◽  
Nonstructural Protein ◽  
Cell Epitope ◽  
Foot And Mouth Disease ◽  
Viral Disease ◽  
In Vitro Transcription ◽  
Mouth Disease ◽  
Mouth Disease Virus ◽  
Foot And Mouth

Foot-and-mouth disease is a highly contagious viral disease of cloven-hoofed animals. The availability of a vaccine for differentiating infected from vaccinated animals (DIVA) is crucial for the control and eradication of Foot-and-mouth disease virus (FMDV). Because traditional inactivated vaccines may contain trace nonstructural proteins interfering with the DIVA, we hypothesized that mutant FMDV with deletion of immunodominant epitopes may be valuable. Our previous study has generated a full-length cDNA clone (pBSAs) of FMDV serotype Asia 1 isolated in China. In this study, a B-cell epitope was identified in the 3A region of a nonstructural protein (NSP) by anti-FMDV cattle sera. Furthermore, we generated recombinant FMDV (rvAs-3A14D) by selectively deleting 14 amino acids (position 91–104) in the 3A region of the NSP. Following in vitro transcription and transfection in BHK-21 cells, we successfully rescued the rvAs-3A14D from BHK-21 cells. Characterization of the rvAs-3A14D revealed that the infectivity, antigenicity, and replication kinetics in BHK-21 cells and virulence in mice of the rvAs-3A14D were similar to that of its parent virus. Notably, the mutant rvAs-3A14D only replicated well in BHK-21 but did poorly in primary calf kidney cells. These data suggest that the recombinant FMDV with deletion of this epitope in the NSP may be potentially used as a candidate inactivated vaccine. Therefore, the application of the marker vaccine and differential diagnostic tests may open a promising new avenue for the development of a vaccine for DIVA.

scholarly journals Immunogenicity evaluation of MS2 phage-mediated chimeric nanoparticle displaying an immunodominant B cell epitope of foot-and-mouth disease virus

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4823 ◽  
Author(s):  
Guoqiang Wang ◽  
Yunchao Liu ◽  
Hua Feng ◽  
Yumei Chen ◽  
Suzhen Yang ◽  
...  
Keyword(s):  
Disease Virus ◽  
Cell Epitope ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Economic Losses ◽  
Peptide Epitopes ◽  
Serotype O ◽  
Mouth Disease Virus ◽  
Foot And Mouth

Foot-and-mouth disease (FMD) is a highly contagious disease of cloven-hoofed animals that has caused tremendous economic losses worldwide. In this study, we designed a chimeric nanoparticles (CNPs) vaccine that displays the predominant epitope of the serotype O foot-and-mouth disease virus (FMDV) VP1 131-160 on the surface of MS2 phage. The recombinant protein was expressed inEscherichia Coliand can self-assemble into CNPs with diameter at 25–30 nmin vitro. A tandem repeat peptide epitopes (TRE) was prepared as control. Mice were immunized with CNPs, TRE and commercialized synthetic peptide vaccines (PepVac), respectively. The ELISA results showed that CNPs stimulated a little higher specific antibody levels to PepVac, but was significantly higher than the TRE groups. Moreover, the results from specific IFN-γ responses and lymphocyte proliferation test indicated that CNP immunized mice exhibited significantly enhanced cellular immune response compared to TRE. These results suggested that the CNPs constructed in current study could be a potential alternative vaccine in future FMDV control.

scholarly journals Transgenic shRNA pigs reduce susceptibility to foot and mouth disease virus infection

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Shengwei Hu ◽  
Jun Qiao ◽  
Qiang Fu ◽  
Chuangfu Chen ◽  
Wei Ni ◽  
...  
Keyword(s):  
Disease Virus ◽  
Clinical Signs ◽  
Foot And Mouth Disease ◽  
Viral Disease ◽  
Mouth Disease ◽  
Swine Industry ◽  
Mouth Disease Virus ◽  
Foot And Mouth ◽  
Interfering Rna

Foot-and-mouth disease virus (FMDV) is an economically devastating viral disease leading to a substantial loss to the swine industry worldwide. A novel alternative strategy is to develop pigs that are genetically resistant to infection. Here, we produce transgenic (TG) pigs that constitutively expressed FMDV-specific short interfering RNA (siRNA) derived from small hairpin RNA (shRNA). In vitro challenge of TG fibroblasts showed the shRNA suppressed viral growth. TG and non-TG pigs were challenged by intramuscular injection with 100 LD50 of FMDV. High fever, severe clinical signs of foot-and-mouth disease and typical histopathological changes were observed in all of the non-TG pigs but in none of the high-siRNA pigs. Our results show that TG shRNA can provide a viable tool for producing animals with enhanced resistance to FMDV.

scholarly journals Foot‐and‐mouth disease virus nonstructural protein 2B interacts with cyclophilin A, modulating virus replication

2018 ◽  
Vol 32 (12) ◽  
pp. 6706-6723 ◽  
Author(s):  
Huisheng Liu ◽  
Qiao Xue ◽  
Weijun Cao ◽  
Fan Yang ◽  
Linna Ma ◽  
...  
Keyword(s):  
Disease Virus ◽  
Virus Replication ◽  
Nonstructural Protein ◽  
Foot And Mouth Disease ◽  
Cyclophilin A ◽  
Mouth Disease ◽  
Mouth Disease Virus ◽  
Foot And Mouth

scholarly journals Factors Required for the Uridylylation of the Foot-and-Mouth Disease Virus 3B1, 3B2, and 3B3 Peptides by the RNA-Dependent RNA Polymerase (3Dpol) In Vitro

2005 ◽  
Vol 79 (12) ◽  
pp. 7698-7706 ◽  
Author(s):  
Arabinda Nayak ◽  
Ian G. Goodfellow ◽  
Graham J. Belsham
Keyword(s):  
Rna Polymerase ◽  
Disease Virus ◽  
Rna Synthesis ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Coding Region ◽  
Mouth Disease Virus ◽  
Foot And Mouth ◽  
Positive Strand Rna

ABSTRACT The 5′ terminus of picornavirus genomic RNA is covalently linked to the virus-encoded peptide 3B (VPg). Foot-and-mouth disease virus (FMDV) is unique in encoding and using 3 distinct forms of this peptide. These peptides each act as primers for RNA synthesis by the virus-encoded RNA polymerase 3Dpol. To act as the primer for positive-strand RNA synthesis, the 3B peptides have to be uridylylated to form VPgpU(pU). For certain picornaviruses, it has been shown that this reaction is achieved by the 3Dpol in the presence of the 3CD precursor plus an internal RNA sequence termed a cis-acting replication element (cre). The FMDV cre has been identified previously to be within the 5′ untranslated region, whereas all other picornavirus cre structures are within the viral coding region. The requirements for the in vitro uridylylation of each of the FMDV 3B peptides has now been determined, and the role of the FMDV cre (also known as the 3B-uridylylation site, or bus) in this reaction has been analyzed. The poly(A) tail does not act as a significant template for FMDV 3B uridylylation.

Delivery of a foot-and-mouth disease virus empty capsid subunit antigen with nonstructural protein 2B improves protection of swine

Vaccine ◽  
2008 ◽  
Vol 26 (45) ◽  
pp. 5689-5699 ◽  
Author(s):  
Lindomar Pena ◽  
Mauro Pires Moraes ◽  
Marla Koster ◽  
Thomas Burrage ◽  
Juan M. Pacheco ◽  
...  
Keyword(s):  
Disease Virus ◽  
Nonstructural Protein ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Empty Capsid ◽  
Mouth Disease Virus ◽  
Foot And Mouth

scholarly journals Lithium chloride inhibits early stages of foot-and-mouth disease virus (FMDV) replication in vitro

2017 ◽  
Vol 89 (11) ◽  
pp. 2041-2046 ◽  
Author(s):  
Fu-Rong Zhao ◽  
Yin-Li Xie ◽  
Ze-Zhong Liu ◽  
Jun-Jun Shao ◽  
Shi-Fang Li ◽  
...  
Keyword(s):  
Disease Virus ◽  
Lithium Chloride ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Early Stages ◽  
Mouth Disease Virus ◽  
Foot And Mouth ◽  
Fmdv Replication

scholarly journals Impairment of the DeISGylation Activity of Foot-and-Mouth Disease Virus Lpro Causes Attenuation In Vitro and In Vivo

2020 ◽  
Vol 94 (13) ◽  
Author(s):  
Gisselle N. Medina ◽  
Paul Azzinaro ◽  
Elizabeth Ramirez-Medina ◽  
Joseph Gutkoska ◽  
Ying Fang ◽  
...  
Keyword(s):  
Disease Virus ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Type I ◽  
Mouth Disease Virus ◽  
Foot And Mouth ◽  
Infected Cells ◽  
Viral Attenuation

ABSTRACT Foot-and-mouth disease virus (FMDV) leader proteinase (Lpro) affects several pathways of the host innate immune response. Previous studies in bovine cells demonstrated that deletions (leaderless [LLV]) or point mutations in Lpro result in increased expression of interferon (IFN) and IFN-stimulated genes (ISGs), including, among others, the ubiquitin-like protein modifier ISG15 and the ubiquitin specific peptidase USP18. In addition to its conventional papain-like protease activity, Lpro acts as a deubiquitinase (DUB) and deISGylase. In this study, we identified a conserved residue in Lpro that is involved in its interaction with ISG15. Mutation W105A rendered Escherichia coli-expressed Lpro unable to cleave the synthetic substrate pro-ISG15 while preserving cellular eIF4G cleavage. Interestingly, mutant FMDV W105A was viable. Overexpression of ISG15 and the ISGylation machinery in porcine cells resulted in moderate inhibition of FMDV replication, along with a decrease of the overall state of ISGylation in wild-type (WT)-infected cells. In contrast, reduced deISGylation was observed upon infection with W105A and leaderless virus. Reduction in the levels of deubiquitination was also observed in cells infected with the FMDV LproW105A mutant. Surprisingly, similarly to WT, infection with W105A inhibited IFN/ISG expression despite displaying an attenuated phenotype in vivo in mice. Altogether, our studies indicate that abolishing/reducing the deISGylase/DUB activity of Lpro causes viral attenuation independently of its ability to block the expression of IFN and ISG mRNA. Furthermore, our studies highlight the potential of ISG15 to be developed as a novel biotherapeutic molecule against FMD. IMPORTANCE In this study, we identified an aromatic hydrophobic residue in foot-and-mouth disease virus (FMDV) leader proteinase (Lpro) (W105) that is involved in the interaction with ISG15. Mutation in Lpro W105 (A12-LproW105A) resulted in reduced deISGylation in vitro and in porcine-infected cells. Impaired deISGylase activity correlated with viral attenuation in vitro and in vivo and did not affect the ability of Lpro to block expression of type I interferon (IFN) and other IFN-stimulated genes. Moreover, overexpression of ISG15 resulted in the reduction of FMDV viral titers. Thus, our study highlights the potential use of Lpro mutants with modified deISGylase activity for development of live attenuated vaccine candidates, and ISG15 as a novel biotherapeutic against FMD.

scholarly journals In vitro comparison of foot-and-mouth disease virus subtype variants causing disease in vaccinated cattle

1978 ◽  
Vol 80 (3) ◽  
pp. 451-459 ◽  
Author(s):  
E. C. Anderson ◽  
W. J. Doughty ◽  
J. Anderson ◽  
D. Baber
Keyword(s):  
Disease Virus ◽  
Vaccine Strain ◽  
Complement Fixation ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Radial Immunodiffusion ◽  
Antibody Concentration ◽  
Mouth Disease Virus ◽  
Foot And Mouth

SummaryFoot-and-mouth disease virus isolates of types O, A and SAT 2, from diseased animals in herds routinely vaccinated twice a year were compared antigenically with the vaccine strains in the complement-fixation, neutralization and radial immunodiffusion tests. It was found that strains which had readily infected vaccinated cattle had R values against the vaccine strain in the complement- fixation and radial immunodiffusion tests of 30 or less, while strains causing primary outbreaks with little spread had R values of 30–40. Threefold differences in humoral neutralizing antibody concentration between the field variant and the vaccine strain in sera from vaccinated animals were likely to be significant in terms of protection.

scholarly journals Foot-and-Mouth Disease Virus Assembly: Processing of Recombinant Capsid Precursor by Exogenous Protease Induces Self-Assembly of Pentamers In Vitro in a Myristoylation-Dependent Manner

2009 ◽  
Vol 83 (21) ◽  
pp. 11275-11282 ◽  
Author(s):  
Stewart Goodwin ◽  
Tobias J. Tuthill ◽  
Armando Arias ◽  
Richard A. Killington ◽  
David J. Rowlands
Keyword(s):  
Disease Virus ◽  
Receptor Binding ◽  
Virus Assembly ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Precursor Protein ◽  
Capsid Precursor ◽  
Mouth Disease Virus ◽  
Foot And Mouth

ABSTRACT The assembly of foot-and-mouth disease virus (FMDV) particles is poorly understood. In addition, there are important differences in the antigenic and receptor binding properties of virus assembly and dissociation intermediates, and these also remain unexplained. We have established an experimental model in which the antigenicity, receptor binding characteristics, and in vitro assembly of capsid precursor can be studied entirely from purified components. Recombinant capsid precursor protein (P1 region) was expressed in E scherichia coli as myristoylated or unmyristoylated protein. The protein sedimented in sucrose gradients at 5S and reacted with monoclonal antibodies which recognize conformational or linear antigen determinants on the virion surface. In addition, it bound the integrin αvβ6, a cellular receptor for FMDV, indicating that unprocessed recombinant capsid precursor is both structurally and antigenically similar to native virus capsid. These characteristics were not dependent on the presence of 2A at the C terminus but were altered by N-terminal myristoylation and in mutant precursors which lacked VP4. Proteolytic processing of myristoylated precursor by recombinant FMDV 3Cpro in vitro induced a shift in sedimentation from 5S to 12S, indicating assembly into pentameric capsid subunits. Nonmyristoylated precursor still assembled into higher-order structures after processing with 3Cpro, but these particles sedimented in sucrose gradients at approximately 17S. In contrast, mutant precursors lacking VP4 were antigenically distinct, were unable to form pentamers, and had reduced capacity for binding integrin receptor. These studies demonstrate the utility of recombinant capsid precursor protein for investigating the initial stages of assembly of FMDV and other picornaviruses.

Sign in / Sign up

Export Citation Format

Share Document