scholarly journals Genetic Determinants of Altered Virulence of Taiwanese Foot-and-Mouth Disease Virus

2000 ◽  
Vol 74 (2) ◽  
pp. 987-991 ◽  
Author(s):  
Clayton W. Beard ◽  
Peter W. Mason

ABSTRACT In 1997, a devastating outbreak of foot-and-mouth disease (FMD) in Taiwan was caused by a serotype O virus (referred to here as OTai) with atypical virulence. It produced high morbidity and mortality in swine but did not affect cattle. We have defined the genetic basis of the species specificity of OTai by evaluating the properties of genetically engineered chimeric viruses created from OTai and a bovine-virulent FMD virus. These studies have shown that an altered nonstructural protein, 3A, is a primary determinant of restricted growth on bovine cells in vitro and significantly contributes to bovine attenuation of OTai in vivo.

2020 ◽  
Vol 94 (13) ◽  
Author(s):  
Gisselle N. Medina ◽  
Paul Azzinaro ◽  
Elizabeth Ramirez-Medina ◽  
Joseph Gutkoska ◽  
Ying Fang ◽  
...  

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.


PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4823 ◽  
Author(s):  
Guoqiang Wang ◽  
Yunchao Liu ◽  
Hua Feng ◽  
Yumei Chen ◽  
Suzhen Yang ◽  
...  

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.


2005 ◽  
Vol 17 (2) ◽  
pp. 242 ◽  
Author(s):  
K. de Haas ◽  
I. Luther ◽  
D. Gerber

Transferred embryos carry the risk of being vehicles of organisms causing diseases. Currently, the risk of in vitro-produced (IVP) embryos is more difficult to assess than the risk of in vivo-derived embryos, since less research has been published on the former. Foot and mouth disease virus (FMDV) is extremely sensitive to a low pH and is likely to be destroyed if embryos are exposed to a low pH for a short time. 2-(N-Morphalino)-ethanesulfonic acid (MES); an organic buffer with pKa 6.1; Sigma, South Africa, M2933) as been shown to destroy FMDV at a rate of 90% per minute at pH 6 and at a rate of 90% per second at pH 5 (Acharya et al. 1990 Vet. Microbiol. 23, 21–34; Thomson “Foot-and-mouth disease,” in Infectious Diseases of Livestock with Special Reference to Southern Africa, ed. Coetzer JAW, Thomson GR, and Tustin RC, Oxford University Press, Cape Town, 825–852). The aim of this study was to test whether exposing bovine oocytes and IVP zygotes to the organic buffer MES, buffered at pH 5.5, is detrimental to the development of bovine IVP embryos. IVM, IVF, and IVC was carried out with 1367 oocytes as described earlier [Jooste et al. 2003 Theriogenology 59, 443]. Oocytes were divided into three groups: 484 were used as controls (no MES exposure); 437 were in a maximal exposure group (MAX), i.e. MES treatment after washing of oocytes, after IVM and after IVF, and 446 had a minimal exposure (MIN), i.e. MES treatment after IVF only. To treat the oocytes with MES, 100 oocytes (from ten droplets) were drawn into a pipette in a maximal volume of 100 μL, and placed in 3 mL of MES, swirled around for 10 s, drawn up again in a maximal volume of 100 μL, and placed in 3 mL of culture medium. Oocytes or zygotes were then washed five times in culture medium before being processed through IVM, IVF, or IVC depending on their stage. Exposure of oocytes to MES varied from 30 to 60 s (10 s swirling and a variable time thereafter to pick up). A chi-square test was used to test for differences in cleavage and Day 7 blastocyst yield between control and treatment groups (P < 0.05). Cleavage (70%; 340/484) and blastocyst yield (32%; 156/484) in the control group were not different from those in MIN (68%; 304/446, and 29%; 131/446, respectively), but were significantly higher than for MAX (57%; 249/437, and 18%; 79/437, respectively). In MAX the MES had a harsh effect on the cumulus cells, making them granular and clumpy in appearance. Oocytes treated in MES solution adhered to the bottom of the dish, which made their handling difficult. Exposure time in MES was therefore variable and longer than initially planned. It is concluded that bovine IVP embryos can be exposed to MES without detrimental effect. Treatment with MAX still resulted in blastocysts but it did not yield good numbers. In future trials, treated dishes should be used to prevent oocyte and zygote adherence. Further research is needed to test whether FMDV can be removed from bovine IVP embryos with the described method.


2019 ◽  
Vol 116 ◽  
pp. 108982 ◽  
Author(s):  
Shi-fang Li ◽  
Mei-jiao Gong ◽  
Yue-feng Sun ◽  
Jun-jun Shao ◽  
Yong-guang Zhang ◽  
...  

2013 ◽  
Vol 100 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Jianxiong Zeng ◽  
Haiwei Wang ◽  
Xiaochun Xie ◽  
Decheng Yang ◽  
Guohui Zhou ◽  
...  

2011 ◽  
Vol 57 (3) ◽  
pp. 169-176 ◽  
Author(s):  
Shuang Li ◽  
Mingchun Gao ◽  
Runxiang Zhang ◽  
Ge Song ◽  
Jun Song ◽  
...  

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.


1963 ◽  
Vol 61 (2) ◽  
pp. 217-230 ◽  
Author(s):  
N. St G. Hyslop ◽  
J. Davie ◽  
Sally P. Carter

Antigenic differences between the strains RV 11 and SA 13/61 of foot-and-mouth disease virus (type SAT 1) were studiedin vivoby cross-protection tests. Cattle inoculated with formolized antigen of either strain developed good immunity to experimental infection with the identical strain but little resistance to the other strain.In vitrothe results of complement fixation tests and of serum-virus neutralization tests in tissue culture were consistent with the observations madein vivo. The results of studies on the serological relationships between four strains of type SAT 1 are presented.The importance of strain differences in the epizootiology and control of the disease is discussed briefly.The authors wish to thank Dr I. A. Galloway and Dr J. B. Brooksby for their advice and criticism, and to acknowledge the valuable technical assistance of Mr K. Herniman, Mr R. L. G. King and Mr E. Scoates.


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