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Natural and vaccine-induced immunity to foot and mouth disease: the prospects for improved vaccines.Revue Scientifique Et Technique... Sep 1996The review considers both the immune responses of livestock to foot and mouth disease (FMD) virus after infection or vaccination, and the characteristics and properties... (Review)
Review
The review considers both the immune responses of livestock to foot and mouth disease (FMD) virus after infection or vaccination, and the characteristics and properties of FMD viruses and vaccines which are relevant to protection. Particular attention is given to possible approaches which could be used to improve conventional vaccines or produce novel vaccines against this most important disease.
Topics: Animals; Antibodies, Viral; Aphthovirus; Carrier State; Cattle; Drug Stability; Foot-and-Mouth Disease; Immunity, Cellular; Immunity, Mucosal; Sheep; Species Specificity; Swine; T-Lymphocytes; Time Factors; Viral Vaccines
PubMed: 9025140
DOI: 10.20506/rst.15.3.955 -
Equine rhinitis A virus and its low pH empty particle: clues towards an aphthovirus entry mechanism?PLoS Pathogens Oct 2009Equine rhinitis A virus (ERAV) is closely related to foot-and-mouth disease virus (FMDV), belonging to the genus Aphthovirus of the Picornaviridae. How picornaviruses...
Equine rhinitis A virus (ERAV) is closely related to foot-and-mouth disease virus (FMDV), belonging to the genus Aphthovirus of the Picornaviridae. How picornaviruses introduce their RNA genome into the cytoplasm of the host cell to initiate replication is unclear since they have no lipid envelope to facilitate fusion with cellular membranes. It has been thought that the dissociation of the FMDV particle into pentameric subunits at acidic pH is the mechanism for genome release during cell entry, but this raises the problem of how transfer across the endosome membrane of the genome might be facilitated. In contrast, most other picornaviruses form 'altered' particle intermediates (not reported for aphthoviruses) thought to induce membrane pores through which the genome can be transferred. Here we show that ERAV, like FMDV, dissociates into pentamers at mildly acidic pH but demonstrate that dissociation is preceded by the transient formation of empty 80S particles which have released their genome and may represent novel biologically relevant intermediates in the aphthovirus cell entry process. The crystal structures of the native ERAV virus and a low pH form have been determined via highly efficient crystallization and data collection strategies, required due to low virus yields. ERAV is closely similar to FMDV for VP2, VP3 and part of VP4 but VP1 diverges, to give a particle with a pitted surface, as seen in cardioviruses. The low pH particle has internal structure consistent with it representing a pre-dissociation cell entry intermediate. These results suggest a unified mechanism of picornavirus cell entry.
Topics: Animals; Aphthovirus; Chlorocebus aethiops; Foot-and-Mouth Disease; Foot-and-Mouth Disease Virus; Hydrogen-Ion Concentration; Picornaviridae; Picornaviridae Infections; RNA, Viral; Respiratory Tract Infections; Viremia
PubMed: 19816570
DOI: 10.1371/journal.ppat.1000620 -
Vaccine Jun 1986Viral recognition of specific receptors in the host cell plasma membrane is the first step in virus infection. Attachment is followed by a redistribution or capping of... (Review)
Review
Viral recognition of specific receptors in the host cell plasma membrane is the first step in virus infection. Attachment is followed by a redistribution or capping of virus particles on the cell surface which may play a role in the uptake process. Certain viruses penetrate the plasma membrane directly but many, both enveloped and non-enveloped viruses, are endocytosed at coated pits and subsequently pass into endosomes. The low pH environment of the endosome facilitates passage of the viral genome into the cytoplasm. For some viruses the mechanism of membrane penetration is now known to be linked to a pH-mediated conformational change in external virion proteins. As a consequence of infection there are alterations in the permeability of the plasma membrane which may contribute to cellular damage. Recent advances in the understanding of these processes are reviewed and their relevance to the development of new strategies for vaccines emphasised.
Topics: Adenoviridae; Amantadine; Animals; Aphthovirus; Cell Line; Cell Membrane; Cell Membrane Permeability; Coated Pits, Cell-Membrane; Endocytosis; Hemagglutinins; Humans; Hydrogen-Ion Concentration; Membrane Fusion; Microscopy, Electron; Microscopy, Electron, Scanning; Orthomyxoviridae; Parainfluenza Virus 1, Human; Picornaviridae; Receptors, Virus; Semliki forest virus; Vacuoles; Viral Vaccines; Virus Physiological Phenomena; Viruses
PubMed: 3014773
DOI: 10.1016/0264-410x(86)90042-3 -
Viruses Oct 2019The aim of this study was to identify respiratory viruses circulating amongst elite racehorses in a training yard by serological testing of serial samples and to...
The aim of this study was to identify respiratory viruses circulating amongst elite racehorses in a training yard by serological testing of serial samples and to determine their impact on health status and ability to race. A six-month longitudinal study was conducted in 30 Thoroughbred racehorses (21 two-year-olds, five three-year-olds and four four-year-olds) during the Flat racing season. Sera were tested for the presence of antibodies against equine herpesvirus 1 and 4 (EHV-1 and EHV-4) and equine rhinitis viruses A and B (ERAV and ERBV) by complement fixation (CF) and equine arteritis virus (EAV) by ELISA. Antibodies against equine influenza (EI) were measured by haemagglutination inhibition (HI). Only ERAV was circulating in the yard throughout the six-month study period. Seroconversion to ERAV frequently correlated with clinical respiratory disease and was significantly associated with subsequent failure to race (p = 0.0009). Over 55% of the two-year-olds in the study seroconverted to ERAV in May and June. In contrast, only one seroconversion to ERAV was observed in the older horses. They remained free of any signs of respiratory disease and raced successfully throughout the study period. The importance of ERAV as a contributory factor in the interruption of training programmes for young horses may be underestimated.
Topics: Animals; Antibodies, Viral; Aphthovirus; Breeding; Horse Diseases; Horses; Longitudinal Studies; Male; Picornaviridae Infections; Respiratory Tract Infections; Running; Sports
PubMed: 31635401
DOI: 10.3390/v11100963 -
The Journal of General Virology Sep 2019Arbidol (ARB, also known as umifenovir) is used clinically in several countries as an anti-influenza virus drug. ARB inhibits multiple enveloped viruses and the primary...
Arbidol (ARB, also known as umifenovir) is used clinically in several countries as an anti-influenza virus drug. ARB inhibits multiple enveloped viruses and the primary mode of action is inhibition of virus entry and/or fusion of viral membranes with intracellular endosomal membranes. ARB is also an effective inhibitor of non-enveloped poliovirus types 1 and 3. In the current report, we evaluate the antiviral potential of ARB against another picornavirus, foot-and-mouth disease virus (FMDV), a member of the genus and an important veterinary pathogen. ARB inhibits the replication of FMDV RNA sub-genomic replicons. ARB inhibition of FMDV RNA replication is not a result of generalized inhibition of cellular uptake of cargo, such as transfected DNA, and ARB can be added to cells up to 3 h post-transfection of FMDV RNA replicons and still inhibit FMDV replication. ARB prevents the recovery of FMDV replication upon withdrawal of the replication inhibitor guanidine hydrochloride (GuHCl). Although restoration of FMDV replication is known to require protein synthesis upon GuHCl removal, ARB does not suppress cellular translation or FMDV internal ribosome entry site (IRES)-driven translation. ARB also inhibits infection with the related equine rhinitis A virus (ERAV). Collectively, the data demonstrate that ARB can inhibit some non-enveloped picornaviruses. The data are consistent with inhibition of picornavirus genome replication, possibly via the disruption of intracellular membranes on which replication complexes are located.
Topics: Animals; Antiviral Agents; Cell Line; Cell Survival; Chlorocebus aethiops; Cricetinae; Foot-and-Mouth Disease Virus; Genome, Viral; Humans; Indoles; Molecular Structure; Virus Replication
PubMed: 31162013
DOI: 10.1099/jgv.0.001283 -
Journal of Virology Dec 1996An oligodeoxynucleotide coding for amino acids 139 through 149 of antigenic site A (ASA) of the VP1 capsid protein of the foot-and-mouth disease virus C3 serotype (FMDV...
An oligodeoxynucleotide coding for amino acids 139 through 149 of antigenic site A (ASA) of the VP1 capsid protein of the foot-and-mouth disease virus C3 serotype (FMDV C3) was inserted into three different in-frame sites of the vesicular stomatitis virus New Jersey serotype (VSV-NJ) glycoprotein (G) gene cDNA present in plasmid pKG97 under control of the bacteriophage T7 polymerase promoter. Transfection of these plasmids into CV1 cells coinfected with the T7 polymerase-expressing vaccinia virus recombinant vTF1-6,2 resulted in expression of chimeric proteins efficiently reactive with both anti-FMDV and anti-VSV G antibodies. However, in vitro translation of transcripts of these VSV-G/FMDV-ASA chimeric plasmids resulted in proteins that were recognized by anti-G serum but not by anti-FMDV serum, indicating a requirement for in vivo conformation to expose the ASA antigenic determinant. Insertion of DNA coding for a dimer of the ASA unidecapeptide between the VSV-NJ G gene region coding for amino acids 160 and 161 gave rise to a chimeric ASA-dimer protein designated GF2d, which reacted twice as strongly with anti-FMDV antibody as did chimeric proteins in which the ASA monomer was inserted in the same position or two other G-gene positions. For even greater expression of chimeric VSV-G/FMDV-ASA proteins, plasmid pGF2d and a deletion mutant p(delta)GF2d (G protein deleted of 324 C-terminal amino acids) were inserted into baculovirus vectors expressing chimeric proteins GF2d-bac and deltaGF2d-bac produced in Sf9 insect cells. Mice vaccinated with three booster injections of 30 microg each of partially purified GF2d-bac protein responded by enzyme-linked immunosorbent assay with FMDV antibody titers of 1,000 units, and those injected with equivalent amounts of deltaGF2d-bac protein showed serum titers of up to 10,000 units. Particularly impressive were FMDV neutralizing antibody titers in serum of mice vaccinated with deltaGF2d-bac protein, which approached those in the sera of mice vaccinated with three 1-microg doses of native FMDV virions. Despite excellent reactivity with native FMDV, the anti-deltaGF2d-bac antibody present in vaccinated mouse serum showed no capacity to bind to sodium dodecyl sulfate (SDS)-denatured FMDV virions and only minimal reactivity with VP1 protein by Western blotting (immunoblotting) after SDS-polyacrylamide gel electrophoresis. It was also shown in a competitive binding assay that a synthetic ASA unidecapeptide, up to concentrations of 200 microg/ml, was quite limited in its ability to inhibit binding of anti-deltaGF2-bac antibody to native FMDV virions. These results suggest that the chimeric VSV-G/FMDV-ASA proteins mimic the capacity of FMDV to raise and react with neutralizing antibodies to a restricted number of ASA conformations present on the surface of native FMDV particles.
Topics: Animals; Antibodies, Viral; Antigens, Viral; Aphthovirus; Baculoviridae; Capsid; Capsid Proteins; Cell Line; Chlorocebus aethiops; Cricetinae; Foot-and-Mouth Disease; Genetic Vectors; Immunogenetics; Membrane Glycoproteins; Neutralization Tests; Precipitin Tests; Recombinant Fusion Proteins; Spodoptera; Vesiculovirus; Viral Envelope Proteins
PubMed: 8970972
DOI: 10.1128/JVI.70.12.8492-8501.1996 -
Virology Sep 1996During serial undiluted passage of a clonal population of foot-and-mouth disease virus (FMDV C-S8c1) in BHK-21 cells, two species of defective RNA were generated and...
During serial undiluted passage of a clonal population of foot-and-mouth disease virus (FMDV C-S8c1) in BHK-21 cells, two species of defective RNA were generated and selected. Sequence analysis revealed that they included deletions within the L-coding region, and retained the correct reading frame for viral protein synthesis. These deleted RNAs directed the synthesis of capsid protein VP1, were packaged in particles sedimenting with standard virus, required homologous infectious helper virus in order to produce viral particles, but did not interfere with the replication of helper virus. While detection of defective particles in FMDV required more than 100 serial passages, once produced, these defective RNAs could be stably maintained upon further passages in the FMDV C-S8c1 quasispecies. Furthermore, a high fitness, monoclonal-antibody-resistant virus was able to replace the standard virus and support the amplification of the deleted particles. This is the first description of naturally occurring, defective particles of FMDV.
Topics: Animals; Aphthovirus; Capsid; Capsid Proteins; Cell Line; Cricetinae; Defective Viruses; Endopeptidases; Gene Deletion; Helper Viruses; RNA, Messenger; RNA, Viral; Serial Passage; Virus Assembly; Virus Replication
PubMed: 8806535
DOI: 10.1006/viro.1996.0450 -
Journal of the Royal Society of Medicine Jan 2002
Topics: Animals; Aphthovirus; Disease Outbreaks; European Union; Foot-and-Mouth Disease; Jurisprudence; Mandatory Reporting; Public Policy; Serologic Tests; United Kingdom; Viral Vaccines
PubMed: 11773341
DOI: 10.1177/014107680209500101 -
PloS One 2018Foot-and-mouth disease (FMD) is a severe infection caused by a picornavirus that affects livestock and wildlife. Persistence in ruminants is a well-documented feature of...
Foot-and-mouth disease (FMD) is a severe infection caused by a picornavirus that affects livestock and wildlife. Persistence in ruminants is a well-documented feature of Foot-and-mouth disease virus (FMDV) pathogenesis and a major concern for disease control. Persistently infected animals harbor virus for extended periods, providing a unique opportunity to study within-host virus evolution. This study investigated the genetic dynamics of FMDV during persistent infections of naturally infected Asian buffalo. Using next-generation sequencing (NGS) we obtained 21 near complete FMDV genome sequences from 12 sub-clinically infected buffalo over a period of one year. Four animals yielded only one virus isolate and one yielded two isolates of different serotype suggesting a serial infection. Seven persistently infected animals yielded more than one virus of the same serotype showing a long-term intra-host viral genetic divergence at the consensus level of less than 2.5%. Quasi-species analysis showed few nucleotide variants and non-synonymous substitutions of progeny virus despite intra-host persistence of up to 152 days. Phylogenetic analyses of serotype Asia-1 VP1 sequences clustered all viruses from persistent animals with Group VII viruses circulating in Pakistan in 2011, but distinct from those circulating on 2008-2009. Furthermore, signature amino acid (aa) substitutions were found in the antigenically relevant VP1 of persistent viruses compared with viruses from 2008-2009. Intra-host purifying selective pressure was observed, with few codons in structural proteins undergoing positive selection. However, FMD persistent viruses did not show a clear pattern of antigenic selection. Our findings provide insight into the evolutionary dynamics of FMDV populations within naturally occurring subclinical and persistent infections that may have implications to vaccination strategies in the region.
Topics: Amino Acid Sequence; Animals; Buffaloes; Cattle; Foot-and-Mouth Disease; Foot-and-Mouth Disease Virus; Genome, Viral; Phylogeny; RNA, Viral; Sequence Alignment
PubMed: 29390015
DOI: 10.1371/journal.pone.0190977 -
Genome Biology and Evolution May 2017The selective pressures acting on viruses that replicate under enhanced mutation rates are largely unknown. Here, we describe resistance of foot-and-mouth disease virus...
The selective pressures acting on viruses that replicate under enhanced mutation rates are largely unknown. Here, we describe resistance of foot-and-mouth disease virus to the mutagen 5-fluorouracil (FU) through a single polymerase substitution that prevents an excess of A to G and U to C transitions evoked by FU on the wild-type foot-and-mouth disease virus, while maintaining the same level of mutant spectrum complexity. The polymerase substitution inflicts upon the virus a fitness loss during replication in absence of FU but confers a fitness gain in presence of FU. The compensation of mutational bias was documented by in vitro nucleotide incorporation assays, and it was associated with structural modifications at the N-terminal region and motif B of the viral polymerase. Predictions of the effect of mutations that increase the frequency of G and C in the viral genome and encoded polymerase suggest multiple points in the virus life cycle where the mutational bias in favor of G and C may be detrimental. Application of predictive algorithms suggests adverse effects of the FU-directed mutational bias on protein stability. The results reinforce modulation of nucleotide incorporation as a lethal mutagenesis-escape mechanism (that permits eluding virus extinction despite replication in the presence of a mutagenic agent) and suggest that mutational bias can be a target of selection during virus replication.
Topics: Amino Acid Substitution; Cell Line; Fluorouracil; Foot-and-Mouth Disease Virus; Genetic Fitness; Kinetics; Models, Molecular; Mutation; Protein Folding; RNA-Dependent RNA Polymerase; Virus Replication
PubMed: 28460010
DOI: 10.1093/gbe/evx075