scholarly journals Novel antibody binding determinants on the capsid surface of serotype O foot-and-mouth disease virus

2014 ◽  
Vol 95 (5) ◽  
pp. 1104-1116 ◽  
Author(s):  
Amin S. Asfor ◽  
Sasmita Upadhyaya ◽  
Nick J. Knowles ◽  
Donald P. King ◽  
David J. Paton ◽  
...  
Keyword(s):  
Amino Acid ◽  
Guinea Pig ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Amino Acid Residues ◽  
Serotype O ◽  
Antigenic Sites ◽  
Mouth Disease Virus ◽  
Foot And Mouth ◽  
The Impact

Five neutralizing antigenic sites have been described for serotype O foot-and-mouth disease viruses (FMDV) based on monoclonal antibody (mAb) escape mutant studies. However, a mutant virus selected to escape neutralization of mAb binding at all five sites was previously shown to confer complete cross-protection with the parental virus in guinea pig challenge studies, suggesting that amino acid residues outside the mAb binding sites contribute to antibody-mediated in vivo neutralization of FMDV. Comparison of the ability of bovine antisera to neutralize a panel of serotype O FMDV identified three novel putative sites at VP2-74, VP2-191 and VP3-85, where amino acid substitutions correlated with changes in sero-reactivity. The impact of these positions was tested using site-directed mutagenesis to effect substitutions at critical amino acid residues within an infectious copy of FMDV O1 Kaufbeuren (O1K). Recovered viruses containing additional mutations at VP2-74 and VP2-191 exhibited greater resistance to neutralization with both O1K guinea pig and O BFS bovine antisera than a virus that was engineered to include only mutations at the five known antigenic sites. The changes at VP2-74 and VP3-85 are adjacent to critical amino acids that define antigenic sites 2 and 4, respectively. However VP2-191 (17 Å away from VP2-72), located at the threefold axis and more distant from previously identified antigenic sites, exhibited the most profound effect. These findings extend our knowledge of the surface features of the FMDV capsid known to elicit neutralizing antibodies, and will improve our strategies for vaccine strain selection and rational vaccine design.

scholarly journals Foot-and-mouth disease virus epitope dominance in the antibody response of vaccinated animals

2012 ◽  
Vol 93 (3) ◽  
pp. 488-493 ◽  
Author(s):  
M. Mahapatra ◽  
P. Hamblin ◽  
D. J. Paton
Keyword(s):  
Disease Virus ◽  
Antigenic Site ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Escape Mutant ◽  
Target Species ◽  
Serotype O ◽  
Antigenic Sites ◽  
Mouth Disease Virus ◽  
Foot And Mouth

Five neutralizing antigenic sites have been identified on the surface of serotype O foot-and-mouth disease virus (FMDV). A set of mAb neutralization-escape mutant viruses was used for the first time to evaluate the relative use of known binding sites by polyclonal antibodies from three target species: cattle, sheep and pigs. Antibodies to all five neutralizing antigenic sites were detected in all three species, with most antibodies directed against antigenic site 2, followed by antigenic site 1. In 76 % of cattle, 65 % of sheep and 58 % of pigs, most antibodies were directed against site 2. Antibodies specific to antigenic sites 3, 4 and 5 were found to be minor constituents in the sera of each of the target species. This implies that antigenic site 2 is a dominant neutralization immunogenic site in serotype O FMDV and may therefore be a good candidate for designing novel vaccines.

Antiviral potential of ivermectin against foot-and-mouth disease virus, serotype O, A and Asia-1

2021 ◽  
pp. 104914
Author(s):  
Zahra Naeem ◽  
Sohail Raza ◽  
Saba Afzal ◽  
Ali Ahmad Sheikh ◽  
Muhammad Muddassir Ali ◽  
...  
Keyword(s):  
Disease Virus ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Serotype O ◽  
Mouth Disease Virus ◽  
Virus Serotype ◽  
Foot And Mouth

scholarly journals Analysis of Amino Acid Mutations of the Foot-and-Mouth Disease Virus Serotype O Using both Heparan Sulfate and JMJD6 Receptors

Viruses ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 1012 ◽  
Author(s):  
Gyeongmin Lee ◽  
Ji-Hyeon Hwang ◽  
Aro Kim ◽  
Jong-Hyeon Park ◽  
Min Ja Lee ◽  
...  
Keyword(s):  
Amino Acid ◽  
Heparan Sulfate ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Amino Acid Sequences ◽  
Cell Adaptation ◽  
Field Virus ◽  
Mouth Disease Virus ◽  
Virus Serotype ◽  
Foot And Mouth

Foot-and-mouth disease (FMD) is an economically devastating animal disease. Adapting the field virus to cells is critical to the vaccine production of FMD viruses (FMDV), and heparan sulfate (HS) and Jumonji C-domain-containing protein 6 (JMJD6) are alternative receptors of cell-adapted FMDV. We performed serial passages of FMDV O/SKR/Andong/2010, classified as the O/Mya-98 topotype/lineage and known as a highly virulent strain, to develop a vaccine seed virus. We traced changes in the amino acid sequences of the P1 region, plaque phenotypes, and the receptor usage of the viruses, and then structurally analyzed the mutations. VP3 H56R and D60G mutations were observed in viruses using the HS receptor and led to changes in the hydrogen bonding between VP3 56 and 60. A VP1 P208L mutation was observed in the virus using the JMJD6 receptor during cell adaptation, enabling the interaction with JMJD6 through the formation of a new hydrogen bond with JMJD6 residue 300. Furthermore, VP1 208 was near the VP1 95/96 amino acids, previously reported as critical mutations for JMJD6 receptor interactions. Thus, the mutation at VP1 208 could be critical for cell adaptation related to the JMJD6 receptor and may serve as a basis for mechanism studies on FMDV cell adaptation.

Quantitative Proteomics by Amino Acid Labeling in Foot-and-Mouth Disease Virus (FMDV)-Infected Cells

2012 ◽  
Vol 12 (1) ◽  
pp. 363-377 ◽  
Author(s):  
Yu Ye ◽  
Guangrong Yan ◽  
Yongwen Luo ◽  
Tiezhu Tong ◽  
Xiangtao Liu ◽  
...  
Keyword(s):  
Amino Acid ◽  
Disease Virus ◽  
Quantitative Proteomics ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Mouth Disease Virus ◽  
Foot And Mouth ◽  
Infected Cells ◽  
Amino Acid Labeling

scholarly journals Predicting antigenic sites on the foot-and-mouth disease virus capsid of the South African Territories types using virus neutralization data

2011 ◽  
Vol 92 (10) ◽  
pp. 2297-2309 ◽  
Author(s):  
F. F. Maree ◽  
B. Blignaut ◽  
J. J. Esterhuysen ◽  
T. A. P. de Beer ◽  
J. Theron ◽  
...  
Keyword(s):  
South African ◽  
Disease Virus ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Sub Saharan Africa ◽  
Antigenic Sites ◽  
Mouth Disease Virus ◽  
Virus Serotype ◽  
Antigenic Properties ◽  
Foot And Mouth

Foot-and-mouth disease virus (FMDV) outer capsid proteins 1B, 1C and 1D contribute to the virus serotype distribution and antigenic variants that exist within each of the seven serotypes. This study presents phylogenetic, genetic and antigenic analyses of South African Territories (SAT) serotypes prevalent in sub-Saharan Africa. Here, we show that the high levels of genetic diversity in the P1-coding region within the SAT serotypes are reflected in the antigenic properties of these viruses and therefore have implications for the selection of vaccine strains that would provide the best vaccine match against emerging viruses. Interestingly, although SAT1 and SAT2 viruses displayed similar genetic variation within each serotype (32 % variable amino acids), antigenic disparity, as measured by r1-values, was less pronounced for SAT1 viruses compared with SAT2 viruses within our dataset, emphasizing the high antigenic variation within the SAT2 serotype. Furthermore, we combined amino acid variation and the r1-values with crystallographic structural data and were able to predict areas on the surface of the FMD virion as antigenically relevant. These sites were mostly consistent with antigenic sites previously determined for types A, O and C using mAbs and escape mutant studies. Our methodology offers a quick alternative to determine antigenic relevant sites for FMDV field strains.

scholarly journals Modifications to the Foot-and-Mouth Disease Virus 2A Peptide: Influence on Polyprotein Processing and Virus Replication

2018 ◽  
Vol 92 (8) ◽  
Author(s):  
Jonas Kjær ◽  
Graham J. Belsham
Keyword(s):  
Amino Acid ◽  
Disease Virus ◽  
Virus Replication ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Amino Acid Substitutions ◽  
2A Peptide ◽  
Polyprotein Processing ◽  
Mouth Disease Virus ◽  
Foot And Mouth

ABSTRACTFoot-and-mouth disease virus (FMDV) has a positive-sense single-stranded RNA (ssRNA) genome that includes a single, large open reading frame encoding a polyprotein. The cotranslational “cleavage” of this polyprotein at the 2A/2B junction is mediated by the 2A peptide (18 residues in length) using a nonproteolytic mechanism termed “ribosome skipping” or “StopGo.” Multiple variants of the 2A polypeptide with this property among the picornaviruses share a conserved C-terminal motif [D(V/I)E(S/T)NPG↓P]. The impact of 2A modifications within this motif on FMDV protein synthesis, polyprotein processing, and virus viability were investigated. Amino acid substitutions are tolerated at residues E14, S15, and N16within the 2A sequences of infectious FMDVs despite their reported “cleavage” efficiencies at the 2A/2B junction of only ca. 30 to 50% compared to that of the wild type (wt). In contrast, no viruses containing substitutions at residue P17, G18, or P19, which displayed little or no “cleavage” activityin vitro, were rescued, but wt revertants were obtained. The 2A substitutions impaired the replication of an FMDV replicon. Using transient-expression assays, it was shown that certain amino acid substitutions at residues E14, S15, N16, and P19resulted in partial “cleavage” of a protease-free polyprotein, indicating that these specific residues are not essential for cotranslational “cleavage.” Immunofluorescence studies, using full-length FMDV RNA transcripts encoding mutant 2A peptides, indicated that the 2A peptide remained attached to adjacent proteins, presumably 2B. These results show that efficient “cleavage” at the 2A/2B junction is required for optimal virus replication. However, maximal StopGo activity does not appear to be essential for the viability of FMDV.IMPORTANCEFoot-and-mouth disease virus (FMDV) causes one of the most economically important diseases of farm animals. Cotranslational “cleavage” of the FMDV polyprotein precursor at the 2A/2B junction, termed StopGo, is mediated by the short 2A peptide through a nonproteolytic mechanism which leads to release of the nascent protein and continued translation of the downstream sequence. Improved understanding of this process will not only give a better insight into how this peptide influences the FMDV replication cycle but may also assist the application of this sequence in biotechnology for the production of multiple proteins from a single mRNA. Our data show that single amino acid substitutions in the 2A peptide can have a major influence on viral protein synthesis, virus viability, and polyprotein processing. They also indicate that efficient “cleavage” at the 2A/2B junction is required for optimal virus replication. However, maximal StopGo activity is not essential for the viability of FMDV.

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