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Clinical Microbiology Reviews Apr 2004Foot-and-mouth disease (FMD) is a highly contagious disease of cloven-hoofed animals. The disease was initially described in the 16th century and was the first animal... (Review)
Review
Foot-and-mouth disease (FMD) is a highly contagious disease of cloven-hoofed animals. The disease was initially described in the 16th century and was the first animal pathogen identified as a virus. Recent FMD outbreaks in developed countries and their significant economic impact have increased the concern of governments worldwide. This review describes the reemergence of FMD in developed countries that had been disease free for many years and the effect that this has had on disease control strategies. The etiologic agent, FMD virus (FMDV), a member of the Picornaviridae family, is examined in detail at the genetic, structural, and biochemical levels and in terms of its antigenic diversity. The virus replication cycle, including virus-receptor interactions as well as unique aspects of virus translation and shutoff of host macromolecular synthesis, is discussed. This information has been the basis for the development of improved protocols to rapidly identify disease outbreaks, to differentiate vaccinated from infected animals, and to begin to identify and test novel vaccine candidates. Furthermore, this knowledge, coupled with the ability to manipulate FMDV genomes at the molecular level, has provided the framework for examination of disease pathogenesis and the development of a more complete understanding of the virus and host factors involved.
Topics: Animals; Disease Outbreaks; Foot-and-Mouth Disease; Foot-and-Mouth Disease Virus; Viral Vaccines
PubMed: 15084510
DOI: 10.1128/CMR.17.2.465-493.2004 -
PLoS Pathogens Aug 2021Long polycytidine (polyC) tracts varying in length from 50 to 400 nucleotides were first described in the 5'-noncoding region (NCR) of genomes of picornaviruses... (Review)
Review
Long polycytidine (polyC) tracts varying in length from 50 to 400 nucleotides were first described in the 5'-noncoding region (NCR) of genomes of picornaviruses belonging to the Cardio- and Aphthovirus genera over 50 years ago, but the molecular basis of their function is still unknown. Truncation or complete deletion of the polyC tracts in picornaviruses compromises virulence and pathogenicity but do not affect replicative fitness in vitro, suggesting a role as "viral security" RNA element. The evidence available suggests that the presence of a long polyC tract is required for replication in immune cells, which impacts viral distribution and targeting, and, consequently, pathogenic progression. Viral attenuation achieved by reduction of the polyC tract length has been successfully used for vaccine strategies. Further elucidation of the role of the polyC tract in viral replication cycle and its connection with replication in immune cells has the potential to expand the arsenal of tools in the fight against cancer in oncolytic virotherapy (OV). Here, we review the published data on the biological significance and mechanisms of action of the polyC tract in viral pathogenesis in Cardio- and Aphthoviruses.
Topics: Animals; Aphthovirus; Cardiovirus; Humans; Oncolytic Virotherapy; Poly C; Virus Replication
PubMed: 34347852
DOI: 10.1371/journal.ppat.1009739 -
Veterinary Research Dec 2013Foot-and-mouth disease (FMD) is a highly contagious disease of cloven-hoofed animals including cattle, pigs, sheep and many wildlife species. It can cause enormous... (Review)
Review
Foot-and-mouth disease (FMD) is a highly contagious disease of cloven-hoofed animals including cattle, pigs, sheep and many wildlife species. It can cause enormous economic losses when incursions occur into countries which are normally disease free. In addition, it has long-term effects within countries where the disease is endemic due to reduced animal productivity and the restrictions on international trade in animal products. The disease is caused by infection with foot-and-mouth disease virus (FMDV), a picornavirus. Seven different serotypes (and numerous variants) of FMDV have been identified. Some serotypes have a restricted geographical distribution, e.g. Asia-1, whereas others, notably serotype O, occur in many different regions. There is no cross-protection between serotypes and sometimes protection conferred by vaccines even of the same serotype can be limited. Thus it is important to characterize the viruses that are circulating if vaccination is being used for disease control. This review describes current methods for the detection and characterization of FMDVs. Sequence information is increasingly being used for identifying the source of outbreaks. In addition such information can be used to understand antigenic change within virus strains. The challenges and opportunities for improving the control of the disease within endemic settings, with a focus on Eurasia, are discussed, including the role of the FAO/EuFMD/OIE Progressive Control Pathway. Better control of the disease in endemic areas reduces the risk of incursions into disease-free regions.
Topics: Animals; Artiodactyla; Asia; Disease Outbreaks; Europe; Foot-and-Mouth Disease; Foot-and-Mouth Disease Virus; Livestock
PubMed: 24308718
DOI: 10.1186/1297-9716-44-116 -
Journal of the American Veterinary... Apr 2004Foot-and-mouth disease (FMD) is caused by an RNA virus of the genus Aphthovirus; 7 immunologically distinct serotypes of the virus have been identified. Susceptible... (Review)
Review
Foot-and-mouth disease (FMD) is caused by an RNA virus of the genus Aphthovirus; 7 immunologically distinct serotypes of the virus have been identified. Susceptible species are mainly domestic and wild even-toed ungulates, such as cattle, sheep, goats, pigs, bison, and deer. All body fluids of infected animals can contain the virus and are considered infective. The primary mode of transmission is animal-to-animal transmission through inhalation or ingestion of aerosols containing the virus. The virus can also be spread mechanically by contaminated organic debris and fomites and can survive for 48 hours on human oral and nasal mucosa and be spread to uninfected animals in this manner. There is a rapid progression of clinical signs after an animal becomes infected, and the virus spreads rapidly throughout a herd. Clinical signs include excessive salivation; fever; vesicles and erosions of the oral and nasal mucosa, coronary band, interdigital area, and teats; lameness; sloughing of claws; reluctance to move; anorexia; mastitis; decreased milk production; and abortion or weak newborns. In mature animals, FMD has high morbidity and low mortality rates. Infected animals can become inapparent carriers of the virus.
Topics: Air Microbiology; Animals; Camelids, New World; Diagnosis, Differential; Disease Reservoirs; Foot-and-Mouth Disease; Foot-and-Mouth Disease Virus; Ruminants; Species Specificity; Swine; Vaccination
PubMed: 15112774
DOI: 10.2460/javma.2004.224.1261 -
Journal of Virology Apr 1992The causative agents of foot-and-mouth disease (FMD) are small icosahedral viruses of the Aphthovirus group within the Picornaviridae family. There is no evidence that... (Review)
Review
The causative agents of foot-and-mouth disease (FMD) are small icosahedral viruses of the Aphthovirus group within the Picornaviridae family. There is no evidence that these viruses infect cells of the immune system or otherwise interfere detrimentally with their function; additionally, it has not been possible to relate cytotoxicity reactions against virus-infected cells to the efficacy of the immune response against FMD virus infection. In contrast, there is a close association between FMD virus antibody and the protective immune response (10, 14, 15, 20, 24, 25, 29-32). Induction of this antibody is dependent on the structure of the viral antigenic sites (7-9, 11, 18) and on the concomitant presence of Th-lymphocyte epitopes (4, 5, 7, 8), although a Th-lymphocyte-independent response has been reported (2). Recent work by Piatti et al. (26) showed that the immune response induced by FMD virus was only Th-lymphocyte dependent when low doses of antigen were used. This latter work was performed in mice, and it is not certain that a similar situation would be found in cattle. As for the major effector immune defense, this relies on the interaction between antibody-virus complexes and the phagocytic cells of the reticuloendothelial system (17, 19).
Topics: Animals; Aphthovirus; Foot-and-Mouth Disease
PubMed: 1312607
DOI: 10.1128/JVI.66.4.1835-1840.1992 -
Intervirology 2009Foot-and-mouth disease virus (FMDV), the prototype member of the Aphthovirus genus, is a single-stranded, positive-sense RNA genome virus, which affects many domestic... (Review)
Review
Foot-and-mouth disease virus (FMDV), the prototype member of the Aphthovirus genus, is a single-stranded, positive-sense RNA genome virus, which affects many domestic livestock cloven-hoofed animals, causing substantial lost of milk in dairy cattle, reduction in the growth rate of meat animals, among others. It has been shown that the virus can enter to the cells using different pathways; the main one binding integrins via the clathrin-mediated endocytosis pathway, trafficking throughout the acidified endocytic vesicles, where its capsid rapidly dissociates, resulting in the release of the RNA genome, and the second one using heparan sulfate in which FMDV enters to the cells using the caveola-mediated endocytosis pathway and that caveolae can associate and traffic with endosomes. Different integrins had been involved as FMDV receptors (alphavbeta1, alphavbeta3, alpha5beta1, alphavbeta6, alphavbeta8); this review will try to resume the basic information about FMDV receptors from the last years to the present and will resume the most important in vitro and in vivo studies to elucidate the role of this receptor on the infection.
Topics: Animals; Foot-and-Mouth Disease Virus; Heparitin Sulfate; Integrins; Receptors, Virus; Virus Attachment; Virus Internalization
PubMed: 19556802
DOI: 10.1159/000226121 -
Wiley Interdisciplinary Reviews. RNA Jul 2021RNA viruses have developed specialized mechanisms to subvert host RNA-binding proteins (RBPs) favoring their own gene expression. The Leader (L) protein of... (Review)
Review
RNA viruses have developed specialized mechanisms to subvert host RNA-binding proteins (RBPs) favoring their own gene expression. The Leader (L) protein of foot-and-mouth disease virus, a member of the Picornaviridae family, is a papain-like cysteine protease that self-cleaves from the polyprotein. Early in infection, the L protease cleaves the translation initiation factors eIF4GI and eIF4GII, inducing the shutdown of cap-dependent translation. However, the cleavage sites on the viral polyprotein, eIF4GI, and eIF4GII differ in sequence, challenging the definition of a consensus site for L targets. Identification of Gemin5 and Daxx proteolytic products in infected cells unveiled a motif centered on the RKAR sequence. The RBP Gemin5 is a member of the survival of motor neurons complex, a ribosome interacting protein, and a translation downregulator. Likewise, the Fas-ligand Daxx is a multifunctional adaptor that plays key roles in transcription control, apoptosis, and innate immune antiviral response. Remarkably, the cleavage site on the RNA helicases MDA5 and LGP2, two relevant immune sensors of the retinoic acid-inducible gene-I (RIG-I)-like receptors family, resembles the L target site of Gemin5 and Daxx, and similar cleavage sites have been reported in ISG15 and TBK1, two proteins involved in type I interferon response and signaling pathway, respectively. In this review we dissect the features of the L cleavage sites in essential RBPs, eventually helping in the discovery of novel L targets. This article is categorized under: RNA in Disease and Development > RNA in Disease Translation > Translation Regulation.
Topics: Animals; Antiviral Restriction Factors; Foot-and-Mouth Disease Virus; Immunity, Innate; RNA; RNA Helicases
PubMed: 33605051
DOI: 10.1002/wrna.1645 -
Biomolecules Jun 2021Foot-and-mouth disease virus (FMDV) is a highly contagious disease that affects cloven-hoofed animals. The traditional diagnostic methods for FMDV have several drawbacks...
Foot-and-mouth disease virus (FMDV) is a highly contagious disease that affects cloven-hoofed animals. The traditional diagnostic methods for FMDV have several drawbacks such as cross-reactivity, low sensitivity, and low selectivity. To overcome these drawbacks, we present an optical and electrochemical dual-modal approach for the specific detection of FMDV serotypes O and A by utilizing a magnetic nanoparticle labeling technique with resorufin β-d-glucopyranoside (res-β-glc) and β-glucosidase (β-glc), without the use of typical lateral flow assay or polymerase chain reaction. FMDV serotypes O and A were reacted with pan-FMDV antibodies that recognize all seven FMDV serotypes (O, A, C, Asia 1, SAT 1, SAT 2, and SAT 3). The antigen-antibody complex was then immobilized on magnetic nanoparticles and reacted with β-glc-conjugated FMDV type O or type A antibodies. Subsequently, the addition of res-β-glc resulted in the release of fluorescent resorufin and glucose owing to catalytic hydrolysis by β-glc. The detection limit of fluorescent signals using a fluorescence spectrophotometer was estimated to be log(6.7) and log(5.9) copies/mL for FMDV type O and A, respectively, while that of electrochemical signals using a glucometer was estimated to be log(6.9) and log(6.1) copies/mL for FMDV type O and A, respectively. Compared with a commercially available lateral flow assay diagnostic kit for immunochromatographic detection of FMDV type O and A, this dual-modal detection platform offers approximately four-fold greater sensitivity. This highly sensitive and accurate dual-modal detection method can be used for effective disease diagnosis and treatment, and will find application in the early-stage diagnosis of viral diseases and next-generation diagnostic platforms.
Topics: Animals; Antibodies, Viral; Electrochemical Techniques; Foot-and-Mouth Disease Virus; Humans; Magnetic Iron Oxide Nanoparticles; Serogroup; Serotyping
PubMed: 34198783
DOI: 10.3390/biom11060841 -
Journal of Virology Jan 2019Like other viruses, the picornavirus foot-and-mouth disease virus (FMDV; genus ), one of the most notorious pathogens in the global livestock industry, needs to navigate...
Like other viruses, the picornavirus foot-and-mouth disease virus (FMDV; genus ), one of the most notorious pathogens in the global livestock industry, needs to navigate antiviral host responses to establish an infection. There is substantial insight into how FMDV suppresses the type I interferon (IFN) response, but it is largely unknown whether and how FMDV modulates the integrated stress response. Here, we show that the stress response is suppressed during FMDV infection. Using a chimeric recombinant encephalomyocarditis virus (EMCV), in which we functionally replaced the endogenous stress response antagonist by FMDV leader protease (L) or 3C, we demonstrate an essential role for L in suppressing stress granule (SG) formation. Consistently, infection with a recombinant FMDV lacking L resulted in SG formation. Additionally, we show that L cleaves the known SG scaffold proteins G3BP1 and G3BP2 but not TIA-1. We demonstrate that the closely related equine rhinitis A virus (ERAV) L also cleaves G3BP1 and G3BP2 and also suppresses SG formation, indicating that these abilities are conserved among aphthoviruses. Neither FMDV nor ERAV L interfered with phosphorylation of RNA-dependent protein kinase (PKR) or eIF2α, indicating that L does not affect SG formation by inhibiting the PKR-triggered signaling cascade. Taken together, our data suggest that aphthoviruses actively target scaffolding proteins G3BP1 and G3BP2 and antagonize SG formation to modulate the integrated stress response. The picornavirus foot-and-mouth disease virus (FMDV) is a notorious animal pathogen that puts a major economic burden on the global livestock industry. Outbreaks have significant consequences for animal health and product safety. Like many other viruses, FMDV must manipulate antiviral host responses to establish infection. Upon infection, viral double-stranded RNA (dsRNA) is detected, which results in the activation of the RNA-dependent protein kinase (PKR)-mediated stress response, leading to a stop in cellular and viral translation and the formation of stress granules (SG), which are thought to have antiviral properties. Here, we show that FMDV can suppress SG formation via its leader protease (L). Simultaneously, we observed that L can cleave the SG scaffolding proteins G3BP1 and G3BP2. Understanding the molecular mechanisms of the antiviral host response evasion strategies of FMDV may help to develop countermeasures to control FMDV infections in the future.
Topics: Animals; Aphthovirus; Cell Line; Cricetinae; Cytoplasmic Granules; Encephalomyocarditis virus; Foot-and-Mouth Disease; Foot-and-Mouth Disease Virus; HEK293 Cells; HeLa Cells; Humans; Peptide Hydrolases; RNA Recognition Motif Proteins; Stress, Physiological; Viral Proteins
PubMed: 30404792
DOI: 10.1128/JVI.00922-18 -
Journal of Virology Nov 2016Equine rhinitis A virus (ERAV) is a picornavirus associated with respiratory disease in horses and is genetically closely related to foot-and-mouth disease virus (FMDV),...
Equine Rhinitis A Virus Mutants with Altered Acid Resistance Unveil a Key Role of VP3 and Intrasubunit Interactions in the Control of the pH Stability of the Aphthovirus Capsid.
UNLABELLED
Equine rhinitis A virus (ERAV) is a picornavirus associated with respiratory disease in horses and is genetically closely related to foot-and-mouth disease virus (FMDV), the prototype aphthovirus. ERAV has recently gained interest as an FMDV alternative for the study of aphthovirus biology, including cell entry and uncoating or antiviral testing. As described for FMDV, current data support that acidic pH inside cellular endosomes triggers ERAV uncoating. In order to provide further insights into aphthovirus uncoating mechanism, we have isolated a panel of ERAV mutants with altered acid sensitivity and that differed on their degree of sensitivity to the inhibition of endosome acidification. These results provide functional evidence of the involvement of acidic pH on ERAV uncoating within endosomes. Remarkably, all amino acid substitutions found in acid-labile or acid-resistant ERAVs were located in the capsid protein VP3, indicating that this protein plays a pivotal role for the control of pH stability of the ERAV capsid. Moreover, all amino acid substitutions mapped at the intraprotomer interface between VP3 and VP2 or between VP3 and the N terminus of VP1. These results expand our knowledge on the regions that regulate the acid stability of aphthovirus capsid and should be taken into account when using ERAV as a surrogate of FMDV.
IMPORTANCE
The viral capsid constitutes a sort of dynamic nanomachine that protects the viral genome against environmental assaults while accomplishing important functions such as receptor attachment for viral entry or genome release. We have explored the molecular determinants of aphthovirus capsid stability by isolating and characterizing a panel of equine rhinitis A virus mutants that differed on their acid sensitivity. All the mutations were located within a specific region of the capsid, the intraprotomer interface among capsid proteins, thus providing new insights into the regions that control the acid stability of aphthovirus capsid. These findings could positively contribute to the development of antiviral approaches targeting aphthovirus uncoating or the refinement of vaccine strategies based on capsid stabilization.
Topics: Acids; Amino Acid Substitution; Animals; Antiviral Agents; Aphthovirus; Capsid; Capsid Proteins; Endosomes; Foot-and-Mouth Disease Virus; Genome, Viral; Horses; Hydrogen-Ion Concentration; Mutation; Picornaviridae Infections; Virus Internalization
PubMed: 27535044
DOI: 10.1128/JVI.01043-16