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Foot-and-mouth disease (FMD) is a contagious viral disease that affects the livelihoods and productivity of livestock farmers in endemic regions. It can infect various domestic and wild animals with cloven hooves and is caused by a virus belonging to the genus Aphthovirus and family Picornaviridae, which has seven different serotypes: A, O, C, SAT1, SAT2, SAT3, and Asia-1. This paper aims to provide a comprehensive overview of the molecular epidemiology, economic impact, diagnosis, and control measures of FMD in Ethiopia in comparison with the global situation. The genetic and antigenic diversity of FMD viruses requires a thorough understanding for developing and applying effective control strategies in endemic areas. FMD has direct and indirect economic consequences on animal production. In Ethiopia, FMD outbreaks have led to millions of USD losses due to the restriction or rejection of livestock products in the international market. Therefore, in endemic areas, disease control depends on vaccinations to prevent animals from developing clinical disease. However, in Ethiopia, due to the presence of diverse antigenic serotypes of FMD viruses, regular and extensive molecular investigation of new field isolates is necessary to perform vaccine-matching studies to evaluate the protective potential of the vaccine strain in the country. [ABSTRACT FROM AUTHOR]

Foot-and-mouth disease virus (FMDV), Senecavirus A (SVA) and swine vesicular disease virus (SVDV) are members of the family Picornaviridae, which can cause similar symptoms - vesicular lesions in the tissues of the mouth, nose, feet, skin and mucous membrane of animals. Rapid and accurate diagnosis of these viruses allows for control measures to prevent the spread of these diseases. Reverse transcription-polymerase chain reaction (RT-PCR) and real-time RT-PCR are traditional and reliable methods for pathogen detection, while their amplification reaction requires a thermocycler. Isothermal amplification methods including loop-mediated isothermal amplification and recombinase polymerase amplification developed in recent years are simple, rapid and do not require specialized equipment, allowing for point of care diagnostics. Luminex technology allows for simultaneous detection of multiple pathogens. CRISPR-Cas diagnostic systems also emerging nucleic acid detection technologies which are very sensitivity and specificity. In this paper, various nucleic acid detection methods aimed at vesicular disease pathogens in swine (including FMDV, SVA and SVDV) are summarized. [ABSTRACT FROM AUTHOR]

Foot-and-mouth disease (FMD) is a great havoc in agri-business-based countries like Bangladesh, for which existing detection system limits the identification and differentiation of serotypes. In this study, an engineered platform was introduced incorporating serotype-specific FMDV VP1 (structural), serotype-independent VP2 (structural) and 3AB (non-structural) proteins for holistic detection. VP1 sequences were engineered combining sequences of BAN/TA/Dh-301/2016 (serotype O), BAN/CH/Sa-304/2016 (serotype A) and BAN/DH/Sa-318/2016 (serotype Asia1). Consensus 3AB sequence was constructed from the selected prevalent viral genomes. Both VP1 and 3AB along with designed VP2 sequences were optimized for codon usage bias, stable mRNA, secondary and tertiary protein structure. Proteins were synthesized in pET-21a (+) plasmid vector followed by transformation of Escherichia coli BL21(DE3) and IPTG-induced- expression. The western blot analysis of engineered proteins showed that purified VP1 prominently bound to anti-VP1 antibodies in vaccinated sera, whereas 3AB and VP2 bound anti-3AB and anti-VP2 antibodies, respectively from infected cattle sera, all previously collected during epidemiological investigation. Furthermore, dot blot hybridization confirmed efficient antibody capture ability of the membrane-immobilized proteins. This holistic diagnostic platform justifies a comprehensive prototype diagnostic kit that would be cost-effective and efficient for serotype specific and non-specific FMDV sero-surveillance. [ABSTRACT FROM AUTHOR]

Macroautophagy/autophagy has been utilized by many viruses, including foot-and-mouth disease virus (FMDV), to facilitate replication, while the underlying mechanism of the interplay between autophagy and innate immune responses is still elusive. This study showed that HDAC8 (histone deacetylase 8) inhibits FMDV replication by regulating innate immune signal transduction and antiviral response. To counteract the HDAC8 effect, FMDV utilizes autophagy to promote HDAC8 degradation. Further data showed that FMDV structural protein VP3 promotes autophagy during virus infection and interacts with and degrades HDAC8 in an AKT-MTOR-ATG5-dependent autophagy pathway. Our data demonstrated that FMDV evolved a strategy to counteract host antiviral activity by autophagic degradation of a protein that regulates innate immune response during virus infection. Abbreviations: 3-MA: 3-methyladenine; ATG: autophagy related; Baf-A1: bafilomycin A1; CCL5: C-C motif chemokine ligand 5; Co-IP: co-immunoprecipitation; CQ: chloroquine phosphate; DAPI: 4",6-diamidino-2-phenylindole; FMDV: foot-and-mouth disease virus; HDAC8: histone deacetylase 8; ISG: IFN-stimulated gene; IRF3: interferon regulatory factor 3; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MOI: multiplicity of infection; MAVS: mitochondria antiviral signaling protein; OAS: 2"−5'-oligoadenylate synthetase; RB1: RB transcriptional corepressor 1; SAHA: suberoylanilide hydroxamic acid; TBK1: TANK binding kinase 1; TCID50: 50% tissue culture infectious doses; TNF/TNF-α: tumor necrosis factor; TSA: trichostatin A; UTR: untranslated region. [ABSTRACT FROM AUTHOR]

Foot-and-mouth disease (FMD), an economically important disease of livestock, is endemic in Botswana. The country has been affected by this disease since the early 1930s, and FMD virus (FMDV) continues to circulate in both domestic and wild animal populations. Botswana is affected by the Southern African Territories (SAT1-3) of FMDV. Up to 80% of the income in the agricultural sector in Botswana is derived from the beef production, and about 70% of Botswana's beef exports go to the European Union (EU) market. Thus, trade restrictions caused by FMD outbreaks may result in declines in revenue. In this review, the FMD status of Botswana from 2006 to 2022 is discussed. During the report period, SAT2 was responsible for 80 out of a total of 87 FMD outbreaks, while SAT1 was responsible for 7 out of 87 outbreaks. These outbreaks were a result of SAT1 topotype I and SAT2 topotypes I, II, and III. There were no outbreaks associated with serotype SAT3 over the review span, suggesting absence of this serotype in the country, although it is still maintained in vaccines formulated for use in Botswana. Most of the outbreaks reported in this review occurred in the North West district of Botswana; an area that is heavily populated with cloven hooved wildlife. This highlights the role of wildlife-domestic animal interaction in FMD spread and maintenance. The Food and Agriculture Organization (FAO) of the United Nations has created a progressive control pathway for FMD (PCP-FMD) for the global elimination of FMD to reduce FMD-related losses. This review highlights how Botswana takes part in the PCP-FMD by putting in place control measures such as surveillance and vaccination. The review also touches on the disease control challenges such as limitations to separation of livestock with populations of buffaloes and lapses in livestock vaccination which contribute to maintenance of FMDV circulation in Botswana. [ABSTRACT FROM AUTHOR]

Senecavirus A (SVA) is a member of the family Picornaviridae and enzootic in domestic swine. SVA can induce vesicular lesions that are clinically indistinguishable from Foot-and-mouth disease, a major cause of global trade barriers and agricultural productivity losses worldwide. The LF-BK αVβ6 cell line is a porcine-derived cell line transformed to stably express an αVβ6 bovine integrin and primarily used for enhanced propagation of Foot-and-mouth disease virus (FMDV). Due to the high biosecurity requirements for working with FMDV, SVA has been considered as a surrogate virus to test and evaluate new technologies and countermeasures. Herein we conducted a series of comparative evaluation in vitro studies between SVA and FMDV using the LF-BK αVβ6 cell line. These include utilization of LF-BK αVβ6 cells for field virus isolation, production of high virus titers, and evaluating serological reactivity and virus susceptibility to porcine type I interferons. These four methodologies utilizing LF-BK αVβ6 cells were applicable to research with SVA and results support the current use of SVA as a surrogate for FMDV. [ABSTRACT FROM AUTHOR]

Foot-and-mouth disease (FMD) remains one of the major threats to animal health worldwide. Its causative agent, the FMD virus (FMDV), affects cloven-hoofed animals, including farm animals and wildlife species, inflicting severe damage to the international trade and livestock industry. FMDV antigenic variability remains one of the biggest challenges for vaccine-based control strategies. The current study analyzed the host's adaptive immune responses in cattle immunized with different vaccine protocols and investigated its associations with the clinical outcome after infection with a heterologous strain of FMDV. The results showed that antigenic payload, multivalency, and revaccination may impact on the clinical outcome after heterologous challenge with FMDV. Protection from the experimental infection was related to qualitative traits of the elicited antibodies, such as avidity, IgG isotype composition, and specificity diversity, modulating and reflecting the vaccine-induced maturation of the humoral response. The correlation analyses of the serum avidity obtained per vaccinated individual might suggest that conventional vaccination can induce high-affinity immunoglobulins against conserved epitopes even within different FMDV serotypes. Cross-reaction among strains by these high-affinity antibodies may support further protection against a heterologous infection with FMDV. [ABSTRACT FROM AUTHOR]

This paper focuses on the development of candidate DNA vaccine encoding antigenic epitopes of type O foot-and-mouth disease virus (FMDV). A series of plasmids encoding different combinations of B cell epitopes and a T cell epitope were constructed and characterized by inoculating BALB/c mice. The specific antibodies were only detectable in the mice inoculated with plasmids encoding the T cell epitope and B cell epitopes from sites 5 and 1, within which site 5 includes residues 135–167 of VP1 and site 1 includes 141–160 region (G–H loop) and carboxyl terminus of VP1. Stronger cellular immune responses were also observed in these mice using T cell proliferation assay. [Copyright &y& Elsevier]

Endoplasmic reticulum (ER) stress-induced autophagy is closely associated with viral infection and propagation. However, the intrinsic link between ER stress, autophagy, and viral replication during foot-and-mouth disease virus (FMDV) infection is not fully elucidated. Our previous studies demonstrated that FMDV infection activated the ER stress-associated UPR of the PERK-eIF2a and ATF6 signaling pathway, whereas the IRE1a signaling was suppressed. We found that the activated-ATF6 pathway participated in FMDV-induced autophagy and FMDV replication, while the IRE1α pathway only affected FMDV replication. Further studies indicated that Sec62 was greatly reduced in the later stages of FMDV infection and blocked the activation of the autophagy-related IRE1α-JNK pathway. Moreover, it was also found that Sec62 promoted IRE1a phosphorylation and negatively regulated FMDV proliferation. Importantly, Sec62 may interact with LC3 to regulate ER stress and autophagy balance and eventually contribute to FMDV clearance via fusing with lysosomes. Altogether, these results suggest that Sec62 is a critical molecule in maintaining and recovering ER homeostasis by activating the IRE1α-JNK pathway and delivering autophagosome into the lysosome, thus providing new insights on FMDV-host interactions and novel antiviral therapies. [ABSTRACT FROM AUTHOR]

RNA interference (RNAi) is a well-conserved mechanism in eukaryotic cells that directs post-transcriptional gene silencing through small RNA molecules. RNAi has been proposed as an alternative approach for rapid and specific control of viruses including foot-and-mouth disease virus (FMDV), the causative agent of a devastating animal disease with high economic impact. The aim of this work was to assess the antiviral activity of different small RNA shuttles targeting the FMDV RNA-dependent RNA polymerase coding sequence (3D). Three target sequences were predicted within 3D considering RNA accessibility as a major criterion. The silencing efficacy of shorthairpin RNAs (shRNAs) and artificial microRNAs (amiRNAs) targeting the selected sequences was confirmed in fluorescent reporter assays. Furthermore, BHK-21 cells transiently expressing shRNAs or amiRNAs proved 70 to >95% inhibition of FMDV growth. Interestingly, dual expression of amiRNAs did not improve FMDV silencing. Lastly, stable cell lines constitutively expressing amiRNAs were established and characterized in terms of antiviral activity against FMDV. As expected, viral replication in these cell lines was delayed. These results show that the target RNA-accessibilityguided approach for RNAi design rendered efficient amiRNAs that constrain FMDV replication. The application of amiRNAs to complement FMDV vaccination in specific epidemiological scenarios shall be explored further. [ABSTRACT FROM AUTHOR]

EFSA received a mandate from the European Commission to assess the effectiveness of some of the control measures against diseases included in the Category A list according to Regulation (EU) 2016/ 429 on transmissible animal diseases ('Animal Health Law'). This opinion belongs to a series of opinions where these control measures will be assessed, with this opinion covering the assessment of control measures for foot and mouth disease (FMD). In this opinion, EFSA and the AHAW Panel of experts review the effectiveness of: i) clinical and laboratory sampling procedures, ii) monitoring period and iii) the minimum radius of the protection and surveillance zones, and the minimum length of time the measures should be applied in these zones. The general methodology used for this series of opinions has been published elsewhere; nonetheless, the transmission kernels used for the assessment of the minimum radius of the protection zone of 3 km and of the surveillance zone of 10 km are shown. Several scenarios for which these control measures had to be assessed were designed and agreed prior to the start of the assessment. The monitoring period of 21 days was assessed as effective, and it was concluded that the protection and the surveillance zones comprise > 99% of the infections from an affected establishment if transmission occurred. Recommendations, provided for each of the scenarios assessed, aim to support the European Commission in the drafting of further pieces of legislation, as well as for plausible ad hoc requests in relation to FMD. [ABSTRACT FROM AUTHOR]

Foot-and-mouth disease (FMD) is a highly contagious disease of cloven-hoofed animals, which has been regarded as a persistent challenge for the livestock industry in many countries. Foot-and-mouth disease virus (FMDV) is the etiological agent of FMD that can spread rapidly by direct and indirect transmission. FMDV is internalized into host cell by the interaction between FMDV capsid proteins and cellular receptors. When the virus invades into the cells, the host antiviral system is quickly activated to suppress the replication of the virus and remove the virus. To retain fitness and host adaptation, various viruses have evolved multiple elegant strategies to manipulate host machine and circumvent the host antiviral responses. Therefore, identification of virus-host interactions is critical for understanding the host defense against virus infections and the pathogenesis of the viral infectious diseases. This review elaborates on the virus-host interactions during FMDV infection to summarize the pathogenic mechanisms of FMD, and we hope it can provide insights for designing effective vaccines or drugs to prevent and control the spread of FMD and other diseases caused by picornaviruses. [ABSTRACT FROM AUTHOR]

Background: Foot-and-mouth disease (FMD) is a highly infectious viral disease, recognised to affect animals in the order Artiodactyla. The disease is rarely fatal in adult animals, however high mortality is associated with neonatal and juvenile infection. Case presentation: Five puppies died after being fed lamb carcases, the lambs having died during an outbreak of FMD in Iran. Following a post-mortem examination, cardiac tissue from one of the dead puppies was subjected to virus isolation, antigen ELISA, real-time RT-PCR, sequencing and confocal microscopy to assess the presence and characteristics of any FMD virus. The virological and microscopic examination of the cardiac tissue provided evidence of FMD virus replication in the canine heart. Conclusions: The data generated in this study demonstrate for the first time that FMD virus can internalise and replicate in dogs and may represent an epidemiologically significant event in FMD transmission, highlighting the dangers of feeding diseased animal carcases to other species. The reporting of this finding may also focus attention on similar disease presentations in dogs in FMD endemic countries allowing a better understanding of the prevalence of such events. [ABSTRACT FROM AUTHOR]

Copyright of Harran University Journal of the Faculty of Veterinary Medicine / Harran Üniversitesi Veteriner Fakültesi Dergisi is the property of Harran University, Faculty of Veterinary Medicine and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Aims: Develop an effective laboratory method to consistently recover viral loads from porous concrete coupons sufficient for disinfectant efficacy testing. Investigate the role of concrete matrix pH on the recovery of foot-and-mouth disease virus (FMDV) and African Swine Fever virus (ASFV) from porous concrete. Compare parameters off FMDV and ASFV inactivation on porous and nonporous surfaces in quantitative carrier tests of a liquid chemical disinfectant. Methods and results: Concrete test coupons were fabricated from commercial and industrial sources and carbonated by exposure to 5% CO2 in a humidified incubator, lowering the matrix pH. Neither dried FMDV nor ASFV were recovered from high-pH concrete control coupons. Recovery of infectious virus from lower pH carbonated concrete was similar to stainless steel coupon controls. Exposure to the liquid disinfectant VirkonTM S inactivated FMDV and ASFV on porous concrete. Conclusions: Concrete matrix pH had a greater impact than surface porosity on the ability to recover viable virus from unsealed concrete. Significance and Impact of the Study: Concrete is commonly found in environments where virus decontamination is required. This study demonstrates a reproducible method to recover sufficient viral loads from porous concrete coupons to facilitate quantitative carrier testing. This method provides a basis for evidence-based validation testing of chemical disinfectants to inactivate pH-sensitive viruses on unsealed concrete. [ABSTRACT FROM AUTHOR]

Foot‐and‐mouth disease virus (FMDV) causes a widely extended contagious disease of livestock. We have previously reported that a synthetic dendrimeric peptide, termed B2T(mal), consisting of two copies of a B‐cell epitope [VP1(140–158)] linked through maleimide groups to a T‐cell epitope [3A(21–35)] of FMDV, elicits potent B‐ and T‐cell‐specific responses and confers solid protection in pigs to type O FMDV challenge. Longer duration of the protective response and the possibility of inducing protection after a single dose are important requirements for an efficient FMD vaccine. Herein, we show that administration of two doses of B2T(mal) elicited high levels of specific total IgGs and neutralizing antibodies that lasted 4–5 months after the peptide boost. Additionally, concomitant levels of IFN‐γ‐producing specific T cells were observed. Immunization with two doses of B2T(mal) conferred a long‐lasting reduced susceptibility to FMDV infection, up to 136 days (19/20 weeks) post‐boost. Remarkably, a similar duration of the protective response was achieved by a single dose of B2T(mal). The effect on the B2T(mal) vaccine of RNA transcripts derived from non‐coding regions in the FMDV genome, known to enhance the immune response and protection induced by a conventional inactivated vaccine, was also analysed. The contribution of our results to the development of FMD dendrimeric vaccines is discussed. [ABSTRACT FROM AUTHOR]

Objective: This research work was conducted for the molecular characterization of the circulating foot-and-mouth disease (FMD) virus in Bangladesh and revealed out their serotype. Materials and methods: The VP1 gene of six field isolates of FMD virus (FMDV) serotypes (two serotypes O, two serotypes A, and two serotypes Asia 1) was subjected for sequencing and phylogenetic analysis. Neighbor-joining trees were constructed by using the Molecular Evolutionary Genetics Analysis 6, having the field nucleotide sequences of FMDV and related sequences available in the GenBank. Results: The nucleotide sequences of the VP1 genes of serotypes O, A, and Asia-1 of the isolates revealed that overall isolates were 91%–100% similar to the isolates reported from Bangladesh and other neighboring countries. Among the isolates reported from Bangladesh, serotype O had 98%–100% identity, serotype A had 91%–100% identity, and serotype Asia-1 had 94%–100% identity. A phylogenetic analysis revealed that the FMDV serotype O PanAsia-02 sub-lineage was confirmed in Bangladesh under the Middle East–South Asian (ME-SA) topotype. On the other hand, we identified genotype VII (18) of Asia topotype (serotype A) and lineage C (serotype Asia-1). Conclusion: The FMDV serotype O PanAsia-02 sub-lineage was confirmed in Bangladesh under the ME-SA topotype for the first time. The extensive cross-border animal movement from neighboring countries may act as the source of diversified FMDV serotypes in Bangladesh. [ABSTRACT FROM AUTHOR]

The study was conducted to observe the overall seroprevalence and molecular detection of circulating FMD virus from infected cattle and efficacy of antibacterial drugs against secondary bacterial infection at Savar, Dhaka from January- December 2018. A total of 92 serum samples were collected for indirect c-ELISA to detect antibodies against non-structural proteins of FMD virus, and overall seroprevalence was 94.02%. The seroprevalence of serotype O and A was higher (95.83% and 95.83%) in male cattle than female (93.18% and 90.91%) respectively. 6 Months to 3 years aged cattle showed, significantly (p<0.01) higher seroprevalence (100%) than above 4 years age groups for serotype O (82.14%) and A (78.57%). Local cattle were more seropositive 96.88% compared to crossbred cattle 93.33% for serotype O and 91.67% for serotype A and this variation was not statistically significant (p>0.05). Among 10 clinical samples of FMD from infected cattle, 8 samples were positive for different serotypes, among them 2 each were identified as serotype A and Asia-1. On the other hand,4 samples were identified as mixed infection (1 sample of serotype O+A, 3 samples of O+Asia-1) by mRT-PCR. In this study on therapeutic intervention with sulphadimidine significantly (p<0.05) reduced the clinical signs of FMD than Gentamycin and Ampicillin. The higher seroprevalence of the disease has substantial economic implications which signify the need for devising effective control measure. However, the detection of 'O', Asia-1and 'A' serotype emphasizes the critical need for use of atrivalent vaccine in the field. [ABSTRACT FROM AUTHOR]

Foot-and-mouth disease (FMD) is an acute, highly contagious, and economically devastating viral disease of domestic and wildlife species. For effective implementation of FMD control program, there is an imperative need for developing a rapid, sensitive, and specific diagnostics which help in the identification of serotypes involved in the outbreaks. The humoral immune response of the Camelidae is unique since in these animals 75% of circulating antibodies are constituted by heavy-chain antibodies and 25% are conventional immunoglobulin with two identical heavy chains. In the present study, we developed and characterized FMD virus-specific single-domain heavy-chain antibodies (VHHs) against inactivated whole-virus antigens of FMDV serotypes O (INDR2/1975), A (IND40/2000), and Asia 1 (IND63/1972) vaccine strains. After six rounds of panning and enrichment, these VHHs were stably expressed in Escherichia coli cells. The VHHs directed against outer capsid proteins of FMD virus were successfully utilized as the capture antibody in liquid-phase blocking ELISA (LPBE) thus replacing rabbit coating antibodies. Our study demonstrated the utility of FMD virus-specific VHHs as potential candidates in FMD research and diagnostic application. [ABSTRACT FROM AUTHOR]

Foot-and-mouth disease virus (FMDV) remains an important pathogen of livestock more than 120 years after it was identified, with annual costs from production losses and vaccination estimated at €5.3–€17 billion (US$6.5–US$21 billion) in FMDV-endemic areas. Control and eradication are difficult because FMDV is highly contagious, genetically and antigenically diverse, infectious for a wide variety of species, able to establish subclinical carriers in ruminants, and widely geographically distributed. For early detection, sustained control, or eradication, sensitive and specific FMDV surveillance procedures compatible with high through-put testing platforms are required. At present, surveillance relies on the detection of FMDV-specific antibody or virus, most commonly in individual animal serum, vesicular fluid, or epithelial specimens. However, FMDV or antibody are also detectable in other body secretions and specimens, e.g., buccal and nasal secretions, respiratory exhalations (aerosols), mammary secretions, urine, feces, and environmental samples. These alternative specimens offer non-invasive diagnostic alternatives to individual animal sampling and the potential for more efficient, responsive, and cost-effective surveillance. Herein we review FMDV testing methods for contemporary and alternative diagnostic specimens and their application to FMDV surveillance in livestock (cattle, swine, sheep, and goats). [ABSTRACT FROM AUTHOR]

Background: Foot-and-mouth disease (FMD) caused by foot-and-mouth disease virus (FMDV) is one of the most highly infectious diseases in livestock, and leads to huge economic losses. Early diagnosis and rapid differentiation of FMDV serotype is therefore integral to the prevention and control of FMD. In this study, a series of serotype-specific reverse transcription recombinase polymerase amplification assays combined with lateral flow dipstick (RPA-LFD) were establish to differentiate FMDV serotypes A, O or Asia 1, respectively. Results: The serotype-specific primers and probes of RPA-LFD were designed to target conserved regions of the FMDV VP1 gene sequence, and three primer and probe sets of serotype-specific RPA-LFD were selected for amplification of FMDV serotypes A, O or Asia 1, respectively. Following incubation at 38 °C for 20 min, the RPA amplification products could be visualized by LFD. Analytical sensitivity of the RPA assay was then determined with ten-fold serial dilutions of RNA of VP1 gene and the recombinant vector respectively containing VP1 gene from FMDV serotypes A, O or Asia1, the detection limits of these assays were 3 copies of plasmid DNA or 50 copies of viral RNA per reaction. Moreover, the specificity of the assay was assessed, and there was no cross reactions with other viruses leading to bovine vesicular lesions. Furthermore, 126 clinical samples were respectively detected with RPA-LFD and real-time PCR (rPCR), there was 98.41% concordance between the two assays, and two samples were positive by RPA-LFD but negative in rPCR, these were confirmed as FMDV-positive through viral isolation in BHK-21 cells. It showed that RPA-LFD assay was more sensitive than the rPCR method in this study. Conclusion: The development of serotype-specific RPA-LFD assay provides a rapid, sensitive, and specific method for differentiation of FMDV serotype A, O or Asia1, respectively. It is possible that the serotype-specific RPA-LFD assay may be used as a integral protocol for field detection of FMDV. [ABSTRACT FROM AUTHOR]

In response to viral infection, cells mount a potent inflammatory response that relies on ISG15 and ubiquitin posttranslational modifications. Many viruses use deubiquitinases and deISGylases that reverse these modifications and antagonize host signaling processes. We here reveal that the leader protease, Lbpro, from foot-and-mouth disease virus (FMDV) targets ISG15 and to a lesser extent, ubiquitin in an unprecedented manner. Unlike canonical deISGylases that hydrolyze the isopeptide linkage after the Cterminal GlyGly motif, Lbpro cleaves the peptide bond preceding the GlyGly motif. Consequently, the GlyGly dipeptide remains attached to the substrate Lys, and cleaved ISG15 is rendered incompetent for reconjugation. A crystal structure of Lbpro bound to an engineered ISG15 suicide probe revealed the molecular basis for ISG15 proteolysis. Importantly, anti-GlyGly antibodies, developed for ubiquitin proteomics, are able to detect Lbpro cleavage products during viral infection. This opens avenues for infection detection of FMDV based on an immutable, host-derived epitope. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Journal of Microbiology is the property of Canadian Science Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Foot-and-mouth disease (FMD) has been a major threat to livestock across the world. The predominant method of controlling this disease in endemic regions is through regular vaccination with inactivated vaccine. However, there are many limitations. For instance, cultivation of virulent FMD virus (FMDV) in the manufacturing units poses a risk of escape from production sites. Vaccines may sometimes contain traces of FMD viral non-structural proteins (NSPs), therefore, interfering with the NSP-based serological differentiation infected from vaccinated animals (DIVA). Moreover, vaccines are unable to eliminate virus from carrier animals. To address the shortcomings of inactivated vaccines, many efforts are currently devoted to develop novel vaccines including attenuated and/or marker inactivated vaccines, recombinant protein vaccines, synthetic peptide vaccines, and empty capsid vaccines. Here, we review the research progress of novel vaccines, problems that remain to be solved, and also raise some suggestions that would help in the development of FMD vaccines. [ABSTRACT FROM PUBLISHER]

Major histocompatibility complex (MHC) class I molecules regulate adaptive immune responses through the presentation of antigenic peptides to CD8+ T cells. Polymorphisms in the peptide binding region of class I molecules determine peptide binding affinity and stability during antigen presentation, and different antigen peptide motifs are associated with specific genetic sequences of class I molecules. Understanding bovine leukocyte antigen (BoLA), peptide-MHC class I binding specificities may facilitate development of vaccines or reagents for quantifying the adaptive immune response to intracellular pathogens, such as foot-and-mouth disease virus (FMDV). Six synthetic BoLA class I (BoLA-I) molecules were produced, and the peptide binding motif was generated for five of the six molecules using a combined approach of positional scanning combinatorial peptide libraries (PSCPLs) and neural network-based predictions ( NetMHCpan). The updated NetMHCpan server was used to predict BoLA-I binding peptides within the P1 structural polyprotein sequence of FMDV (strain A24 Cruzeiro) for BoLA-1*01901, BoLA-2*00801, BoLA-2*01201, and BoLA-4*02401. Peptide binding affinity and stability were determined for these BoLA-I molecules using the luminescent oxygen channeling immunoassay (LOCI) and scintillation proximity assay (SPA). The functional diversity of known BoLA alleles was predicted using the MHCcluster tool, and functional predictions for peptide motifs were compared to observed data from this and prior studies. The results of these analyses showed that BoLA alleles cluster into three distinct groups with the potential to define 'BoLA supertypes.' This streamlined approach identifies potential T cell epitopes from pathogens, such as FMDV, and provides insight into T cell immunity following infection or vaccination. [ABSTRACT FROM AUTHOR]