scholarly journals Molecular Mechanisms of Foot-and-Mouth Disease Virus Targeting the Host Antiviral Response

2017 ◽  
Vol 7 ◽  
Author(s):  
Miguel Rodríguez Pulido ◽  
Margarita Sáiz
Keyword(s):  
Disease Virus ◽  
Molecular Mechanisms ◽  
Foot And Mouth Disease ◽  
Antiviral Response ◽  
Mouth Disease ◽  
Mouth Disease Virus ◽  
Foot And Mouth ◽  
Host Antiviral Response

scholarly journals The Foot-and-Mouth Disease Carrier State Divergence in Cattle

2016 ◽  
Vol 90 (14) ◽  
pp. 6344-6364 ◽  
Author(s):  
Carolina Stenfeldt ◽  
Michael Eschbaumer ◽  
Steven I. Rekant ◽  
Juan M. Pacheco ◽  
George R. Smoliga ◽  
...  
Keyword(s):  
Foot And Mouth Disease ◽  
Antiviral Response ◽  
Carrier State ◽  
Gamma Interferon ◽  
Mouth Disease ◽  
Fmdv Infection ◽  
Mouth Disease Virus ◽  
Follicle Associated Epithelium ◽  
Foot And Mouth ◽  
Host Antiviral Response

ABSTRACTThe pathogenesis of persistent foot-and-mouth disease virus (FMDV) infection was investigated in 46 cattle that were either naive or had been vaccinated using a recombinant, adenovirus-vectored vaccine 2 weeks before challenge. The prevalence of FMDV persistence was similar in both groups (62% in vaccinated cattle, 67% in nonvaccinated cattle), despite vaccinated cattle having been protected from clinical disease. Analysis of antemortem infection dynamics demonstrated that the subclinical divergence between FMDV carriers and animals that cleared the infection had occurred by 10 days postinfection (dpi) in vaccinated cattle and by 21 dpi in nonvaccinated animals. The anatomic distribution of virus in subclinically infected, vaccinated cattle was restricted to the pharynx throughout both the early and the persistent phases of infection. In nonvaccinated cattle, systemically disseminated virus was cleared from peripheral sites by 10 dpi, while virus selectively persisted within the nasopharynx of a subset of animals. The quantities of viral RNA shed in oropharyngeal fluid during FMDV persistence were similar in vaccinated and nonvaccinated cattle. FMDV structural and nonstructural proteins were localized to follicle-associated epithelium of the dorsal soft palate and dorsal nasopharynx in persistently infected cattle. Host transcriptome analysis of tissue samples processed by laser capture microdissection indicated suppression of antiviral host factors (interferon regulatory factor 7, CXCL10 [gamma interferon-inducible protein 10], gamma interferon, and lambda interferon) in association with persistent FMDV. In contrast, during the transitional phase of infection, the level of expression of IFN-λ mRNA was higher in follicle-associated epithelium of animals that had cleared the infection. This work provides novel insights into the intricate mechanisms of FMDV persistence and contributes to further understanding of this critical aspect of FMDV pathogenesis.IMPORTANCEThe existence of a prolonged, asymptomatic carrier state is a political impediment for control and potential eradication of foot-and-mouth disease (FMD). When FMD outbreaks occur, they are often extinguished by massive depopulation of livestock due to the fear that some animals may have undiagnosed subclinical infection, despite uncertainty over the biological relevance of FMD virus (FMDV) persistence. The work described here elucidates aspects of the FMDV carrier state in cattle which may facilitate identification and/or abrogation of asymptomatic FMDV infection. The divergence between animals that clear infection and those that develop persistent infection was demonstrated to occur earlier than previously established. The host antiviral response in tissues maintaining persistent FMDV was downregulated, whereas upregulation of IFN-λ mRNA was found in the epithelium of cattle that had recently cleared the infection. This suggests that the clearing of FMDV infection is associated with an enhanced mucosal antiviral response, whereas FMDV persistence is associated with suppression of the host antiviral response.

scholarly journals Molecular Mechanisms of Immune Escape for Foot-and-Mouth Disease Virus

Pathogens ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 729
Author(s):  
Bo Yang ◽  
Xiaohui Zhang ◽  
Dajun Zhang ◽  
Jing Hou ◽  
GuoWei Xu ◽  
...  
Keyword(s):  
Immune Responses ◽  
Disease Virus ◽  
Molecular Mechanisms ◽  
Immune Escape ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Host Immune Responses ◽  
Mouth Disease Virus ◽  
Foot And Mouth ◽  
Vesicular Disease

Foot-and-mouth disease virus (FMDV) causes a highly contagious vesicular disease in cloven-hoofed livestock that results in severe consequences for international trade, posing a great economic threat to agriculture. The FMDV infection antagonizes the host immune responses via different signaling pathways to achieve immune escape. Strategies to escape the cell immune system are key to effective infection and pathogenesis. This review is focused on summarizing the recent advances to understand how the proteins encoded by FMDV antagonize the host innate and adaptive immune responses.

scholarly journals The pH Stability of Foot-and-Mouth Disease Virus Particles Is Modulated by Residues Located at the Pentameric Interface and in the N Terminus of VP1

2015 ◽  
Vol 89 (10) ◽  
pp. 5633-5642 ◽  
Author(s):  
Flavia Caridi ◽  
Angela Vázquez-Calvo ◽  
Francisco Sobrino ◽  
Miguel A. Martín-Acebes
Keyword(s):  
Disease Virus ◽  
Molecular Mechanisms ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Acid Sensitivity ◽  
Mouth Disease Virus ◽  
N Terminus ◽  
Foot And Mouth ◽  
Capsid Stability ◽  
Acid Labile

ABSTRACTThe picornavirus foot-and-mouth disease virus (FMDV) is the etiological agent of a highly contagious disease that affects important livestock species. The FMDV capsid is highly acid labile, and viral particles lose infectivity due to their disassembly at pH values slightly below neutrality. This acid sensitivity is related to the mechanism of viral uncoating and genome penetration from endosomes. In this study, we have analyzed the molecular basis of FMDV acid-induced disassembly by isolating and characterizing a panel of novel FMDV mutants differing in acid sensitivity. Amino acid replacements altering virion stability were preferentially distributed in two different regions of the capsid: the N terminus of VP1 and the pentameric interface. Even more, the acid labile phenotype induced by a mutation located at the pentameric interface in VP3 could be compensated by introduction of an amino acid substitution in the N terminus of VP1. These results indicate that the acid sensitivity of FMDV can be considered a multifactorial trait and that virion stability is the fine-tuned product of the interaction between residues from different capsid proteins, in particular those located within the N terminus of VP1 or close to the pentameric interface.IMPORTANCEThe viral capsid protects the viral genome from environmental factors and contributes to virus dissemination and infection. Thus, understanding of the molecular mechanisms that modulate capsid stability is of interest for the basic knowledge of the biology of viruses and as a tool to improve the stability of conventional vaccines based on inactivated virions or empty capsids. Using foot-and-mouth disease virus (FMDV), which displays a capsid with extreme acid sensitivity, we have performed a genetic study to identify the molecular determinants involved in capsid stability. A panel of FMDV mutants with differential sensitivity to acidic pH was generated and characterized, and the results showed that two different regions of FMDV capsid contribute to modulating viral particle stability. These results provide new insights into the molecular mechanisms of acid-mediated FMDV uncoating.

scholarly journals Genetic Determinants of Virulence between Two Foot-and-Mouth Disease Virus Isolates Which Caused Outbreaks of Differing Severity

mSphere ◽  
2019 ◽  
Vol 4 (4) ◽  
Author(s):  
Tatsuya Nishi ◽  
Kazuki Morioka ◽  
Nobuko Saito ◽  
Makoto Yamakawa ◽  
Toru Kanno ◽  
...  
Keyword(s):  
Disease Virus ◽  
Molecular Mechanisms ◽  
Three Dimensional ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Genetic Determinants ◽  
Replication Fidelity ◽  
Suckling Mice ◽  
Mouth Disease Virus ◽  
Foot And Mouth

ABSTRACT Individual foot-and-mouth disease virus (FMDV) strains reveal different degrees of infectivity and pathogenicity in host animals. The differences in severity among outbreaks might be ascribable to these differences in infectivity among FMDV strains. To investigate the molecular mechanisms underlying these differences, we estimated the infectivity of O/JPN/2000 and O/JPN/2010, which caused outbreaks of markedly different scales, in cell lines, Holstein cattle, and suckling mice. Viral growth of the two strains in cells was not remarkably different; however, O/JPN/2000 showed apparently low transmissibility in cattle. Mortality rates of suckling mice inoculated intraperitoneally with a 50% tissue culture infective dose (TCID50) of 10 for O/JPN/2000 and O/JPN/2010 also differed, at 0% and 100%, respectively. To identify genes responsible for this difference in infectivity, genetic regions of the full-length cDNA of O/JPN/2010 were replaced with corresponding fragments of O/JPN/2000. A total of eight recombinant viruses were successfully recovered, and suckling mice were intraperitoneally inoculated. Strikingly, recombinants having either VP1 or 3D derived from O/JPN/2000 showed 0% mortality in suckling mice, whereas other recombinants showed 100% mortality. This finding indicates that VP1, the outermost component of the virus particle, and 3D, an RNA-dependent RNA polymerase, are individually involved in the virulence of O/JPN/2010. Three-dimensional structural analysis of VP1 confirmed that amino acid differences between the two strains were located mainly at the domain interacting with the cellular receptor. On the other hand, measurement of their mutation frequencies demonstrated that O/JPN/2000 had higher replication fidelity than O/JPN/2010. IMPORTANCE Efforts to understand the universal mechanism of foot-and-mouth disease virus (FMDV) infection may be aided by knowledge of the molecular mechanisms which underlie differences in virulence beyond multiple topotypes and serotypes of FMDV. Here, we demonstrated independent genetic determinants of two FMDV isolates which have different transmissibility in cattle, namely, VP1 and 3D protein. Findings suggested that the selectivity of VP1 for host cell receptors and replication fidelity during replication were important individual factors in the induction of differences in virulence in the host as well as in the severity of outbreaks in the field. These findings will aid the development of safe live vaccines and antivirals which obstruct viral infection in natural hosts.

scholarly journals The cis-responsive element of Foot-and-mouth disease virus interacts with host cellular factor PCBP2 dependent on host specificity

2021 ◽  
Author(s):  
JaeHun Cheong ◽  
Jeong A Jang ◽  
Bok Kyung Ku
Keyword(s):  
Disease Virus ◽  
Molecular Mechanisms ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Genome Replication ◽  
Viral Pathogen ◽  
Cellular Factor ◽  
Mouth Disease Virus ◽  
Foot And Mouth ◽  
Responsive Element

Abstract I. Background: Foot-and-mouth disease virus (FMDV) is a highly contagious viral pathogen in cloven-hoofed animal including cattle and pig, yet progress in the molecular mechanisms of FMDV genome replication is notably lagging behind that for many RNA viruses. A positive single stranded RNA of FMDV encodes a single long open reading frame flanked by a long 5’-untranslated region (5’UTR) and a short 3’-UTR. The cis-responsive element (CRE) of 5’UTR is critical for FMDV genome replication. II. Methods and Results: Here, we described that poly(C)-binding protein 2 (PCBP2) is revealed as a CRE-binding cellular factor. The RNA immunoprecipitation experiment confirmed that the FMDV CRE interacts with PCBP2 protein. CRE derived from FMDV infection in pig bound stronger to PCBP2 protein of pig than cattle PCBP2, showing host specific RNA-protein interaction. In addition, PCBP2 interacts with FMDV 3B protein together with CRE. The interaction of PCBP and 3B protein with CRE also showed host-specific manners. III. Conclusions: These data suggest that cellular PCBP2 may serve as a host cellular factor of FMDV to facilitate viral replication through interaction with the viral genome and contribute to determine host susceptibility of FMDV variants. The inter-molecular interaction between cellular PCBP2 and FMDV 3B and CRE provides perspectives for antiviral strategy.

High resolution surface structure of foot-and-mouth disease virus

1978 ◽  
Vol 36 (2) ◽  
pp. 376-377
Author(s):  
S. S. Breese ◽  
H. L. Bachrach
Keyword(s):  
Electron Microscopy ◽  
High Resolution ◽  
Surface Structure ◽  
Disease Virus ◽  
Potassium Phosphate ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Physical Measurements ◽  
Mouth Disease Virus ◽  
Foot And Mouth

Models for the structure of foot-and-mouth disease virus (FMDV) have been proposed from chemical and physical measurements (Brown, et al., 1970; Talbot and Brown, 1972; Strohmaier and Adam, 1976) and from rotational image-enhancement electron microscopy (Breese, et al., 1965). In this report we examine the surface structure of FMDV particles by high resolution electron microscopy and compare it with that of particles in which the outermost capsid protein VP3 (ca. 30, 000 daltons) has been split into smaller segments, two of which VP3a and VP3b have molecular weights of about 15, 000 daltons (Bachrach, et al., 1975).Highly purified and concentrated type A12, strain 119 FMDV (5 mg/ml) was prepared as previously described (Bachrach, et al., 1964) and stored at 4°C in 0. 2 M KC1-0. 5 M potassium phosphate buffer at pH 7. 5. For electron microscopy, 1. 0 ml samples of purified virus and trypsin-treated virus were dialyzed at 4°C against 0. 2 M NH4OAC at pH 7. 3, deposited onto carbonized formvar-coated copper screens and stained with phosphotungstic acid, pH 7. 3.

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