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Introduction: Coxsackievirus A6 (CV-A6) has emerged as the predominant epidemic strain responsible for hand, foot and mouth disease (HFMD). CV-A6 infection can result in severe clinical manifestations, including encephalitis, meningitis, and potentially life-threatening central nervous system disorders. Our previous research findings demonstrated that neonatal mice infected with CV-A6 exhibited limb weakness, paralysis, and ultimately succumbed to death. However, the underlying mechanism of CV-A6-induced nervous system injury remains elusive. Numerous reports have highlighted the pivotal role of miRNAs in various viral infections. Methods: Separately established infection and control groups of mice were used to create miRNA profiles of the brain tissues before and after CV-A6 transfection, followed by experimental verification, prediction, and analysis of the results. Results: At 2 days post-infection (dpi), 4 dpi, and 2dpi vs 4dpi, we identified 175, 198 and 78 significantly differentially expressed miRNAs respectively using qRT-PCR for validation purposes. Subsequently, we predicted target genes of these differentially expressed miRNAs and determined their potential targets through GO (Gene Ontology) enrichment analysis and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis. Finally, we verified the miRNA-mRNA pairing via double luciferase experiments while confirming functional enrichment of target genes through Western Blotting analyses. Discussion: The results from this study suggest that transcriptional regulation, neuronal necrosis, pro-inflammatory cytokine release, and antiviral immunity are all implicated in the pathogenesis of central nervous systeminjury in mice infected with CV-A6. Brain injury resulting from CV-A6 infection may involve multiple pathways, including glial cell activation, neuronal necrosis, synaptic destruction, degenerative diseases of the nervous system. It can even encompass destruction of the blood-brain barrier, leading to central nervous system injury. The dysregulated miRNAs and signaling pathways discovered in this study provide valuable insights for further investigations into the pathogenesis of CV-A6. [ABSTRACT FROM AUTHOR]

Hand, foot, and mouth disease (HFMD) is a prevalent acute infectious disease caused by enteroviruses, presenting substantial public health challenges in Shanghai, especially among children. The dynamic nature of HFMD's etiology necessitates an ongoing evaluation of its epidemiological and virological trends to inform effective control strategies. This study aims to investigate the epidemiological patterns and viral evolution of HFMD in Fengxian District, Shanghai, China, with a focus on shifts in predominant viral strains over a 14-year period. We conducted a retrospective analysis of HFMD cases reported to the National Notifiable Disease Reporting System in Fengxian District from January 1, 2009 to December 31, 2022. Epidemiological trends, strain prevalence, and demographic impacts were assessed. A total of 27,272 HFMD cases were documented during the study period, with incidence showing pronounced seasonal fluctuations—peaking in spring and summer and a lesser peak in autumn. The disease incidence demonstrated significant positive correlations with several meteorological variables: daily average temperature (r = 0.30, P < 0.05), relative humidity (r = 0.20, P < 0.05), wind speed (r = 0.17, P < 0.05), and precipitation (r = 0.17, P < 0.05). Geographically, Nanqiao Town, Fengcheng Town, and Xidu Subdistrict reported the highest incidence rates. The demographic analysis revealed a male-to-female ratio of 1.60:1, predominantly affecting children aged 1–3 years. Prior to 2017, Enterovirus 71 (EV71) and Coxsackievirus A16 (CoxA16) were the primary detected strains; post-2017, Coxsackievirus A6 (CoxA6) emerged as the dominant strain. Statistical analysis confirmed significant year-to-year variations in virus detection rates, with decreasing trends for EV71 and other enteroviruses and an increasing trend for CoxA6. The findings indicate a distinct seasonal incidence of HFMD in Fengxian District. This study underscores the need for targeted public health education, enhanced surveillance, and proactive measures in childcare facilities to mitigate disease spread during peak seasons. Moreover, the evolving viral landscape warrants accelerated efforts in vaccine development against new strains to reduce HFMD incidence. [ABSTRACT FROM AUTHOR]

Macroautophagy/autophagy and apoptosis are pivotal interconnected host cell responses to viral infection, including picornaviruses. Here, the VP3 proteins of picornaviruses were determined to trigger autophagy, with the autophagic flux being triggered by the TP53-BAD-BAX axis. Using foot-and-mouth disease virus (FMDV) as a model system, we unraveled a novel mechanism of how picornavirus hijacks autophagy to bolster viral replication and enhance pathogenesis. FMDV infection induced both autophagy and apoptosis in vivo and in vitro. FMDV VP3 protein facilitated the phosphorylation and translocation of TP53 from the nucleus into the mitochondria, resulting in BAD-mediated apoptosis and BECN1-mediated autophagy. The amino acid Gly129 in VP3 is essential for its interaction with TP53, and crucial for induction of autophagy and apoptosis. VP3-induced autophagy and apoptosis are both essential for FMDV replication, while, autophagy plays a more important role in VP3-mediated pathogenesis. Mutation of Gly129 to Ala129 in VP3 abrogated the autophagic regulatory function of VP3, which significantly decreased the viral replication and pathogenesis of FMDV. This suggested that VP3-induced autophagy benefits viral replication and pathogenesis. Importantly, this Gly is conserved and showed a common function in various picornaviruses. This study provides insight for developing broad-spectrum antivirals and genetic engineering attenuated vaccines against picornaviruses. Abbreviations: 3-MA, 3-methyladenine; ATG, autophagy related; BAD, BCL2 associated agonist of cell death; BAK1, BCL2 antagonist/killer 1; BAX, BCL2 associated X, apoptosis regulator; BBC3/PUMA, BCL2 binding component 3; BCL2, BCL2 apoptosis regulator; BID, BH3 interacting domain death agonist; BIP-V5, BAX inhibitor peptide V5; CFLAR/FLIP, CASP8 and FADD like apoptosis regulator; CPE, cytopathic effects; CQ, chloroquine; CV, coxsackievirus; DAPK, death associated protein kinase; DRAM, DNA damage regulated autophagy modulator; EV71, enterovirus 71; FMDV, foot-and-mouth disease virus; HAV, hepatitis A virus; KD, knockdown; MAP1LC3/LC3, microtubule associated protein 1 light chain 3; MOI, multiplicity of infection; MTOR, mechanistic target of rapamycin kinase; PML, promyelocytic leukemia; PV, poliovirus; SVA, Seneca Valley virus; TCID50, 50% tissue culture infectious doses; TOR, target of rapamycin. TP53/p53, tumor protein p53; WCL, whole-cell lysate. [ABSTRACT FROM AUTHOR]

Foot-and-mouth disease (FMD) is a highly contagious viral disease of clovenhoofed animals responsible for economic losses that amount to >$20 billion annually. Rapid recognition of FMD cases provides vital information to guide control programmes. A range of point-of-need amplification technologies have been developed which allow sensitive detection of the causative virus (FMDV) in the field at locations remote from laboratories. Here we describe a novel system to detect FMDV RNA using loop-mediated isothermal amplification (LAMP). This test was evaluated using a panel of FMDV isolates (n = 79) and RNA standards demonstrating capability to amplify viral genome directly from clinical material in the absence of nucleic acid extraction. This extraction-free RT-LAMP assay was transferred to a bespoke closed-system lateral flow test (LFT) that was used in combination with a low-cost hand-held heater. Our results show that the RT-LAMP-LFT assay retains a high level of diagnostic and analytical sensitivity when using direct clinical material, with a limit of detection under 80 copies per reaction. Together, our data support the potential for the use of this assay at the point-of-need to facilitate rapid feedback on the status of suspect cases. [ABSTRACT FROM AUTHOR]

The WD40 domain is one of the most abundant domains and is among the top interacting domains in eukaryotic genomes. The WD40 domain of ATG16L1 is essential for LC3 recruitment to endolysosomal membranes during non-canonical autophagy, but dispensable for canonical autophagy. Canonical autophagy was utilized by FMDV, while the relationship between FMDV and non-canonical autophagy is still elusive. In the present study, WD40 knockout (KO) PK15 cells were successfully generated via CRISPR/cas9 technology as a tool for studying the effect of non-canonical autophagy on FMDV replication. The results of growth curve analysis, morphological observation and karyotype analysis showed that the WD40 knockout cell line was stable in terms of growth and morphological characteristics. After infection with FMDV, the expression of viral protein, viral titers, and the number of copies of viral RNA in the WD40-KO cells were significantly greater than those in the wild-type PK15 cells. Moreover, RNA‒seq technology was used to sequence WD40-KO cells and wild-type cells infected or uninfected with FMDV. Differentially expressed factors such as Mx1, RSAD2, IFIT1, IRF9, IFITM3, GBP1, CXCL8, CCL5, TNFRSF17 were significantly enriched in the autophagy, NOD-like receptor signaling pathway, RIG-I-like receptor signaling pathway, Toll-like receptor signaling pathway, cytokine-cytokine receptor interaction and TNF signaling pathway, etc. The expression levels of differentially expressed genes were detected via qRT‒PCR, which was consistent with the RNA‒seq data. Here, we experimentally demonstrate for the first time that knockout of the WD40 domain of ATG16L1 enhances FMDV replication by downregulation innate immune factors. In addition, this result also indicates non-canonical autophagy inhibits FMDV replication. In total, our results play an essential role in regulating the replication level of FMDV and providing new insights into virus–host interactions and potential antiviral strategies. Importance: FMDV is a pathogen that causes highly contagious animal disease worldwide. The WD40 domain of ATG16L1 is necessary for non-canonical autophagy, while dispensable for canonical autophagy. Thus, the WD40 knockout PK15 cell line established by present study could use as a tool to research the impact of non-canonical autophagy on FMDV replication. The results showed that knockout of the WD40 domain of ATG16L1 in PK15 cells could enhance FMDV replication. The results also showed that differentially expressed innate immune factors, such as Mx1, IFIT1, RSAD2, and IRF9, were significantly enriched in the interferon signaling pathway. Our research also indicates non-canonical autophagy inhibits FMDV replication by innate immune, which helps to elucidate the role of the non-canonical autophagy in the host antiviral strategies. [ABSTRACT FROM AUTHOR]

Epidemic trajectories can be substantially impacted by people modifying their behaviours in response to changes in their perceived risk of spreading or contracting the disease. However, most infectious disease models assume a stable population behaviour. We present a flexible new class of models, called behavioural change individual‐level models (BC‐ILMs), that incorporate both individual‐level covariate information and a data‐driven behavioural change effect. Focusing on spatial BC‐ILMs, we consider four “alarm” functions to model the effect of behavioural change as a function of infection prevalence over time. Through simulation studies, we find that if behavioural change is present, using an alarm function, even if specified incorrectly, will result in an improvement in posterior predictive performance over a model that assumes stable population behaviour. The methods are applied to data from the 2001 U.K. foot and mouth disease epidemic. The results show some evidence of a behavioural change effect, although it may not meaningfully impact model fit compared to a simpler spatial ILM in this dataset. [ABSTRACT FROM AUTHOR]

Foot-and-mouth disease (FMD) is a severe, highly contagious viral disease of livestock that has a significant economic impact on domestic animals and threatens wildlife survival in China and border countries. However, effective surveillance and prevention of this disease is often incomplete and unattainable due to the cost, the great diversity of wildlife hosts, the changing range and dynamics, and the diversity of FMDV. In this study, we used predictive models to reveal the spread and risk of FMD in anticipation of identifying key nodes to control its spread. For the first time, the spatial distribution of FMD serotype O was predicted in western China and border countries using a niche model, which is a combination of eco-geographic, human, topographic, and vegetation variables. The transboundary least-cost pathways (LCPs) model for ungulates in the study area were also calculated. Our study indicates that FMD serotype O survival is seasonal at low altitudes (March and June) and more sensitive to temperature differences at high altitudes. FMD serotype O risk was higher in Central Asian countries and both were highly correlated with the population variables. Ten LCPs were obtained representing Pakistan, Kazakhstan, Kyrgyzstan, and China. [ABSTRACT FROM AUTHOR]

Foot and mouth disease (FMD) is a highly contagious viral disease affecting cloven-hoofed animals. This disease is one of the most important in animal health due to its significant socio-economic impact, especially in case of an outbreak. One important challenge associated with this disease is the ability of the FMD virus (FMDV) to persist in its hosts through still unresolved underlying mechanisms. The absence of relevant in vitro models is one factor preventing advancement in our understanding of FMDV persistence. While a primary bovine cell model has been established using cells from FMDV primary and persistence site in cattle, it appeared interesting to develop a similar model based on ovine anatomical sites of interest to compare host-pathogen interactions. Thus, epithelial cells derived from the palatine tonsils and the dorsal soft palate were isolated and cultured. Their epithelial nature was confirmed using immunofluorescence. Following monolayer infection with FMDV O/FRA/1/2001 Clone 2.2, the FMDV-sensitivity of these cells was evaluated. Dorsal soft palate (DSP) cells were also expanded in multilayers at the air-liquid interface to mimic a stratified epithelium sensitive to FMDV infection. Our investigation revealed the presence of infectious virus, as well as viral antigens and viral RNA, up to 35 days after infection of the cell multilayers. Further experiment with DSP cells from different individuals needs to be reproduced to confirm the robustness of the new model of persistence in multilayer DSP. The establishment of such primary cells creates new opportunities for FMDV research and analysis in sheep cells. [ABSTRACT FROM AUTHOR]

Foot-and-mouth disease (FMD) is a highly infectious and endemic disease in Lao PDR. However, surveillance is weak, and outbreaks are not routinely reported. To address this, serum samples were routinely collected from cattle and buffalo from provincial abattoirs between November 2021 and December 2022. A total of 2,663 serum samples were collected from large ruminants (n = 1,625 cattle; n = 1,038 buffalo) from 17 provinces. Samples were tested for specific antibodies directed against FMD non-structural protein (NSP) to determine the proportion of animals exposed to FMD virus. In addition to sampling from abattoirs, further independent data was collected to report clinical signs and outcomes from 94 districts in 12 northern provinces. These incident reports were recorded by district staff using a Google Form and summarised monthly in the National Animal Disease Reporting System. Information was collected on species, incident date, herd size, location and which clinical signs the animals presented. Overall, 46% of the tested animals returned a positive result using ID Screen® FMD NSP Competition ELISA. Results from serological testing were then compared with reported clinical signs from the same district. In districts reporting 'mouth problems' (regardless of other clinical signs) the median FMD seroprevalence was 49.7%, compared to 31.6% in districts not reporting mouth problems (p = 0.021). This finding suggests that reporting clinical cases of 'mouth problems' could be a potential predictor of FMD infection at a district level in cattle and buffalo in Lao PDR. Furthermore, in districts reporting 'fever', 'mouth problems', and 'nose/mouth secretions' together, the median FMD seroprevalence was 46.2%, compared to 24.4% in districts not reporting these signs (p = 0.033). In districts reporting 'mouth problems' and 'nose/mouth secretions' the median FMD seroprevalence was 49.4%, compared to 25.5% in districts not reporting these signs (p = 0.037). In districts reporting both 'fever' and 'mouth problems,' the median FMD seroprevalence was 46.4% compared to 25% in districts not reporting these signs (p = 0.017). Based on serological data generated by abattoir surveillance, this study identified clinical signs most predictive of FMD seroprevalence. These novel findings can be used to guide passive surveillance efforts in the future specifically in northern Laos and help support improved FMD surveillance more broadly in FMD endemic countries in Southeast Asia. [ABSTRACT FROM AUTHOR]

Practical Application Collagens are conventionally derived from bovine and porcine sources. However, these sources were commonly associated with infectious diseases such as bovine spongiform encephalopathy, foot and mouth disease, autoimmune and allergic reactions, and religious constraints. The significant amount of collagen available in marine species, especially fish skins, scales, fins, and bones, shows that marine species can be a potential alternative source to mammalian collagen. Therefore, this review aims to give a clearer outlook on the processing techniques of marine collagen and its physicochemical and bioactive properties as a potential alternative to mammalian collagen. The two most suitable extraction methods for marine collagen are pepsin‐soluble extraction and ultrasound‐assisted extraction. Additionally, marine collagen's physicochemical and bioactive properties, such as antioxidants, wound healing, tissue engineering, and cosmetic biomaterial have been thoroughly discussed in this review.Collagen extracted from marine sources showed its potential in physicochemical and bioactive properties, including antioxidants and wound‐healing capabilities, as an alternative to mammalian collagen. The significant amount of collagen found in marine species, particularly in fish skins, scales, bones, and sea cucumbers, suggests that marine sources could be a viable alternative to land mammal collagen due to their abundance and accessibility. The ultrasound‐assisted extraction technique has improved the extracted marine collagen's physicochemical and bioactivity properties and quality properties. [ABSTRACT FROM AUTHOR]

Introduction: Understanding multi-pathogen infections/exposures in livestock is critical to inform prevention and control measures against infectious diseases. We investigated the co-exposure of foot-and-mouth disease virus (FMDV), Brucella spp., Leptospira spp., and Coxiella burnetii in cattle in three zones stratified by land use change and with different wildlife-livestock interactions in Narok county, Kenya. We also assessed potential risk factors associated with the transmission of these pathogens in cattle. Methods: We identified five villages purposively, two each for areas with intensive (zone 1) and moderate wildlife-livestock interactions (zone 2) and one for locations with low wildlife-livestock interactions (zone 3). We sampled 1,170 cattle from 390 herds through a cross-sectional study and tested the serum samples for antibodies against the focal pathogens using enzymelinked immunosorbent assay (ELISA) kits. A questionnaire was administered to gather epidemiological data on the putative risk factors associated with cattle's exposure to the investigated pathogens. Data were analyzed using the Bayesian hierarchical models with herd number as a random effect to adjust for the within-herd clustering of the various co-exposures among cattle. Results: Overall, 88.0% (95% CI: 85.0-90.5) of the cattle tested positive for at least one of the targeted pathogens, while 41.7% (95% CI: 37.7-45.8) were seropositive to at least two pathogens. FMDV and Brucella spp. had the highest co-exposure at 33.7% (95% CI: 30.9-36.5), followed by FMDV and Leptospira spp. (21.8%, 95% CI: 19.5-24.4), Leptospira spp. and Brucella spp. (8.8%, 95% CI: 7.2-10.6), FMDV and C. burnetii (1.5%, 95% CI: 0.7-2.8), Brucella spp. and C. burnetii (1.0%, 95% CI: 0.3-2.2), and lowest for Leptospira spp. and C. burnetii (0.3%, 95% CI: 0.0-1.2). Cattle with FMDV and Brucella spp., and Brucella spp. and Leptospira spp. co-exposures and those simultaneously exposed to FMDV, Brucella spp. and Leptospira spp. were significantly higher in zone 1 than in zones 2 and 3. However, FMDV and Leptospira spp. co-exposure was higher in zones 1 and 2 than zone 3. Discussion/conclusion: We recommend the establishment of a One Health surveillance system in the study area to reduce the morbidity of the targeted zoonotic pathogens in cattle and the risks of transmission to humans. [ABSTRACT FROM AUTHOR]

Background and Aim: Foot-and-mouth disease (FMD) is a highly contagious viral disease of cloven-footed animals. It is a major threat to livestock production worldwide, causing significant economic losses. Inactivation of FMD virus (FMDV) is crucial for vaccine development and control of outbreaks. However, traditional inactivation methods can sometimes damage the viral protein, affecting vaccine efficacy. Therefore, finding new inactivating agents that effectively inactivate the virus while preserving the integrity of its proteins is an important research area. This study investigated the optimal materials (0.04% formaldehyde, 0.001 M binary ethylenimine [BEI], or a combination) for inactivating and preserving the specific molecular weight of Serotype O FMDV protein. Materials and Methods: This study used serotype O FMDV isolated from several areas of East Java. The virus was inoculated into baby hamster kidney-21 cells, and the titer was calculated using the TCID50 Assay. The virus was inactivated using 0.04% formaldehyde, 0.001 M BEI, or a combination of 0.04% formaldehyde and 0.001 M BEI. Inactive viral proteins were characterized using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and western blotting. Results: Serotype O FMDV can be inactivated using 0.04% formaldehyde while preserving specific FMDV proteins, specifically VP0 and VP3 with a molecular weight (MW) of 36 kDa and VP3 with a MW of 24 kDa. Serotype O FMDV can be inactivated by 0.001 M BEI while preserving specific FMDV proteins, specifically VP0 with a MW of 35 kDa, VP3 with a MW of 28 kDa, and VP1 with a MW of 23 kDa. FMDV serotype O can be inactivated using a combination of 0.04% formaldehyde and 0.001 M BEI while preserving specific FMDV proteins, specifically VP0 and VP3 with a MW of 36 kDa and VP3 with a MW of 24 kDa. Conclusion: This study found that 0.04% formaldehyde, alone or in combination with 0.001 M BEI, was effective for inactivating and preserving the specific molecular weight of Serotype O FMDV protein. The limitation of this study was the inactivations of the virus have not yet been tested for their potency on experimental animals. Further research is warranted to investigate the inactivation kinetics of these materials, including their potency on experimental animals. Additionally, a comparison of the inactivation rates between 0.04% formaldehyde alone and the combination with BEI would help to determine the optimal inactivation agent for future applications. [ABSTRACT FROM AUTHOR]

Infectious disease dynamics operate across biological scales: pathogens replicate within hosts but transmit among populations. Functional changes in the pathogen-host interaction thus generate cascading effects across organizational scales. We investigated within-host dynamics and among-host transmission of three strains (SAT-1, -2, -3) of foot-and-mouth disease viruses (FMDVs) in their wildlife host, African buffalo. We combined data on viral dynamics and host immune responses with mathematical models to ask the following questions: How do viral and immune dynamics vary among strains? Which viral and immune parameters determine viral fitness within hosts? And how do within-host dynamics relate to virus transmission? Our data reveal contrasting within-host dynamics among viral strains, with SAT-2 eliciting more rapid and effective immune responses than SAT-1 and SAT-3. Within-host viral fitness was overwhelmingly determined by variation among hosts in immune response activation rates but not by variation among individual hosts in viral growth rate. Our analyses investigating across-scale linkages indicate that viral replication rate in the host correlates with transmission rates among buffalo and that adaptive immune activation rate determines the infectious period. These parameters define the virus's relative basic reproductive number (ℛ0), suggesting that viral invasion potential may be predictable from within-host dynamics. [ABSTRACT FROM AUTHOR]

An HFMD outbreak spread over the city of Hải Phòng from summer 2011 to autumn 2012. This epidemic was chosen because it was the very first HFMD epidemic in North Vietnam, eliminating thus interferences with previous outbreaks. This epidemic displayed three separate waves. A complete dataset was collected for more than 9500 patients during this period, which enabled us to analyze this epidemic at different scales. Access to the healthcare system was crucial during this period, which was possible due to a reorganization of the system in February–March 2012. An analysis at the commune level enabled us to track the epidemic along certain communication routes. The three-waves structure reveals a wide disparity at the district level. We developed a mathematical model showing high accuracy at the adjustment of data for both the total number of cases and for the number of cases per week. As a consequence, the model was able to accurately determine the dates of the beginning and end of each wave and to show that they overlapped. Using mathematical functions associated with this model, it was possible to calculate the probability for a patient to belong to a specific wave. [ABSTRACT FROM AUTHOR]

Since 1998, notifiable bluetongue virus (BTV) serotypes 1-4, 6, 8, 9, 11, and 16 have been reported in Europe. In August 2006, a bluetongue (BT) outbreak caused by BTV serotype 8 began in northwestern Europe. The Netherlands was declared BT-free in February 2012, and annual monitoring continued. On September 3, 2023, typical BT clinical manifestations in sheep were notified to the Netherlands Food and Product Safety Consumer Authority. On September 6, we confirmed BTV infection through laboratory diagnosis; notifications of clinical signs in cattle were also reported. We determined the virus was serotype 3 by whole-genome sequencing. Retrospective analysis did not reveal BTV circulation earlier than September. The virus source and introduction route into the Netherlands remains unknown. Continuous monitoring and molecular diagnostic testing of livestock will be needed to determine virus spread, and new prevention strategies will be required to prevent BTV circulation within the Netherlands and Europe. [ABSTRACT FROM AUTHOR]

Background:Hand foot mouth disease (HFMD), a disease of childhood is also reported in adults caused by Coxsackie virus A type 16. Clinical condition is characterized by vesicular eruptive lesion in mouth, hand, foot, buttock, or genitalia. Coxsackie virus is a member of picoranaviridae family that includes non-enveloped SSRNA viruses. Spread in humans in the case of HFMD is through oral route, by the shed virus from intestine of infected person or through upper respiratory tract by the secretions or vesicle fluid of the diseased individual. Incubation period is 3 to 6 days. Diagnosis of HFMD most of the time is based clinically depending on the patient’s age, symptoms and clinical presentation of rash. Samples include stool, oral samples, biopsy & vesicular scrapings. Viral culture is the gold standard. Treatment is mainly supportive, to maintain hydration, acetaminophen and NSAIDS to reduce temperature. Novel agents like pleconaril play a vital role in the management of viral infection cases. Hand hygiene is the main stay of prevention. [ABSTRACT FROM AUTHOR]

Enhancing livestock biosecurity is critical to safeguard the livelihoods of farmers, global and local economies, and food security. Vaccination is fundamental to the control and prevention of exotic and endemic high-priority infectious livestock diseases. Successful implementation of vaccination in a biosecurity plan is underpinned by a strong understanding of correlates of protection--those elements of the immune response that can reliably predict the level of protection from viral challenge. While correlates of protection have been successfully characterized for many human viral vaccines, for many highpriority livestock viral diseases, including African swine fever and foot and mouth disease, they remain largely uncharacterized. Current literature provides insights into potential correlates of protection that should be assessed during vaccine development for these high-priority mammalian livestock viral diseases. Establishment of correlates of protection for biosecurity purposes enables immune surveillance, rationale for vaccine development, and successful implementation of livestock vaccines as part of a biosecurity strategy. [ABSTRACT FROM AUTHOR]

Hand, foot and mouth disease (HFMD), mainly caused by enterovirus 71 (EV71), has frequently occurred in the Asia-Pacific region, posing a significant threat to the health of infants and young children. Therefore, research on the infection mechanism and pathogenicity of enteroviruses is increasingly becoming important. The 3D polymerase, as the most critical RNA-dependent RNA polymerase (RdRp) for EV71 replication, is widely targeted to inhibit EV71 infection. In this study, we identified a novel host protein, AIMP2, capable of binding to 3D polymerase and inhibiting EV71 infection. Subsequent investigations revealed that AIMP2 recruits the E3 ligase SMURF2, which mediates the polyubiquitination and degradation of 3D polymerase. Furthermore, the antiviral effect of AIMP2 extended to the CVA16 and CVB1 serotypes. Our research has uncovered the dynamic regulatory function of AIMP2 during EV71 infection, revealing a novel antiviral mechanism and providing new insights for the development of antienteroviral therapeutic strategies. [ABSTRACT FROM AUTHOR]

This study aimed to establish an economical and rapid response system for carcass leachate leakage using a real-time groundwater monitoring system with sensors. In this work, four parameters, namely electrical conductivity (EC), chloride (Cl), nitrate nitrogen (NO3-N), and ammonia nitrogen (NH4-N), were monitored. Three actual livestock burial sites were selected as pilot areas and monitored for three years, from 2019 to 2021, using these four parameters. As a result of sensor quality control, the accuracy and precision range of the four parameters were found to be acceptable, within 75~125% and ±25%, respectively. When compared to the laboratory measurement value, the field measurement value recorded by the sensors was 1.1 times higher for EC, 1.6 times higher for Cl, and 2.5 times higher for NO3-N. The correlation analysis between the lab measurement and sensor measurement results showed that the EC had the highest correlation coefficient of 0.3837. Additionally, the factor extraction results showed that the EC showed a relatively significant correlation compared to the other parameters. In summary, based on the results of this study, EC may be considered a key sensor parameter for evaluating leachate leakage from groundwater near disposal sites. [ABSTRACT FROM AUTHOR]

Senecavirus A (SVA) is a picornavirus that is endemic in swine, causing a vesicular disease clinically indistinguishable from other vesicular diseases, like foot-and-mouth disease. The widespread viral circulation, constant evolution, and economic losses caused to the swine industry emphasize the need for measures to control the agent. In this study, we evaluated the immunogenicity of a whole-virus-inactivated vaccine using a representative contemporary Brazilian SVA strain in Balb/ByJ mice. The animals were vaccinated with two doses by an intramuscular route. The humoral response induced by the vaccination was evaluated by an in-house ELISA assay for IgG detection. The cellular response was assessed by flow cytometry after in vitro SVA stimulation in splenocyte cultures from vaccinated and non-vaccinated groups. Protection against SVA was assessed in the experimental groups following an oral challenge with the homologous virus. The vaccination induced high levels of IgG antibodies and the proliferation of CD45R/B220+sIgM+, CD3e+CD69+, and CD3e+CD4+CD44+CD62L− cells. These results indicate the immunogenicity and safety of the vaccine formulation in a murine model and the induction of humoral and cellular response against SVA. [ABSTRACT FROM AUTHOR]

Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) has recently gained prominence for its ability to provide molecular and spatial information in tissue sections. This technology has the potential to uncover novel insights into proteins and other molecules in biological and immunological pathways activated along diseases with a complex host-pathogen interaction, such as animal tuberculosis. Thus, the present study conducted a data analysis of protein signature in granulomas of cattle and pigs naturally infected with the Mycobacterium tuberculosis complex (MTC), identifying biological and immunological signaling pathways activated throughout the disease. Lymph nodes from four pigs and four cattle, positive for the MTC by bacteriological culture and/or real-time PCR, were processed for histopathological examination andMALDI-MSI. Protein identities were assigned using the MaTisse database, and protein-protein interaction networkswere visualized using the STRING database. Gene Ontology (GO) analysis was carried out to determine biological and immunological signaling pathways in which these proteins could participate together with Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Distinct proteomic profiles between cattle and pig granulomas were displayed. Noteworthy, the GO analysis revealed also common pathways among both species, such as "Complement activation, alternative pathway" and "Tricarboxylic acid cycle", which highlight pathways that are conserved among different species infected by the MTC. In addition, speciesspecific terms were identified in the current study, such as "Natural killer cell degranulation" in cattle or those related to platelet and neutrophil recruitment and activation in pigs. Overall, this study provides insights into the immunopathogenesis of tuberculosis in cattle and pigs, opening new areas of research and highlighting the importance, among others, of the complement activation pathway and the regulation of natural killer cell- and neutrophil-mediated immunity in this disease. [ABSTRACT FROM AUTHOR]

Background: Foot and mouth disease is a contagious, transboundary, and economically devastating viral disease of cloven-hoofed animals. The disease can cause many consequences, including decreased productivity, limited market access, and elimination of flocks or herds. This study aimed to assess farmers' willingness to pay (WTP) for foot and mouth disease (FMD) vaccines and identify factors influencing their WTP. A cross-sectional questionnaire survey was conducted on 396 randomly selected livestock-owning farmers from three districts in the central Oromia region (Ambo, Dendi, and Holeta districts. The study utilized the contingent valuation method, specifically employing dichotomous choice bids with double bounds, to evaluate the willingness to pay (WTP) for the FMD vaccine. Mean WTP was assessed using interval regression, and influential factors were identified. Results: The study revealed that the farmer's mean willingness to pay for a hypothetical foot and mouth disease vaccine was 37.5 Ethiopian Birr (ETB) [95% confidence interval [CI]: 34.5 40.58] in all data, while it was 23.84 (95% CI: 21.47–26.28) in the mixed farming system and 64.87 Ethiopian Birr (95% CI: 58.68 71.15) in the market-oriented farming system. We identified main livelihood, management system, sales income, breed, keeping animals for profit, and foot and mouth disease impact perception score as significant variables (p ≤ 0.05) determining the farmers' WTP for the FMD vaccine. Conclusion: Farmers demonstrated a high computed willingness to pay, which can be considered an advantage in the foot and mouth disease vaccination program in central Oromia. Therefore, it is necessary to ensure sufficient vaccine supply services to meet the high demand revealed. [ABSTRACT FROM AUTHOR]

Background: Foot-and-mouth disease (FMD) is a devastating disease affecting cloven-hoofed animals, that leads to significant economic losses in affected countries and regions. Currently, there is an evident inclination towards the utilization of nanoparticles as powerful platforms for innovative vaccine development. Therefore, this study developed a ferritin-based nanoparticle (FNP) vaccine that displays a neutralizing epitope of foot-and-mouth disease virus (FMDV) VP1 (aa 140–158) on the surface of FNP, and evaluated the immunogenicity and protective efficacy of these FNPs in mouse and guinea pig models to provide a strategy for developing potential FMD vaccines. Results: This study expressed the recombinant proteins Hpf, HPF-NE and HPF-T34E via an E. coli expression system. The results showed that the recombinant proteins Hpf, Hpf-NE and Hpf-T34E could be effectively assembled into nanoparticles. Subsequently, we evaluated the immunogenicity of the Hpf, Hpf-NE and Hpf-T34E proteins in mice, as well as the immunogenicity and protectiveness of the Hpf-T34E protein in guinea pigs. The results of the mouse experiment showed that the immune efficacy in the Hpf-T34E group was greater than the Hpf-NE group. The results from guinea pigs immunized with Hpf-T34E showed that the immune efficacy was largely consistent with the immunogenicity of the FMD inactivated vaccine (IV) and could confer partial protection against FMDV challenge in guinea pigs. Conclusions: The Hpf-T34E nanoparticles stand out as a superior choice for a subunit vaccine candidate against FMD, offering effective protection in FMDV-infected model animals. FNP-based vaccines exhibit excellent safety and immunogenicity, thus representing a promising strategy for the continued development of highly efficient and safe FMD vaccines. [ABSTRACT FROM AUTHOR]

Introduction: Hand, foot, and mouth disease (HFMD) outbreaks are increasingly occurring in workplace child centres, highlighting the need for preventive measures. Both child centre caregivers and parents play a crucial role in preventing the spread of the disease, as it can be brought from home and quickly transmitted within the premises. Thus, this study aims to determine the level of HFMD preventive practice and the predictors among parents who enrol their children at the workplace child centre in Pahang. Materials and methods: A cross-sectional study was conducted by distributing a self-administered questionnaire to 163 parents who sent their children to workplace child centres selected via stratified random sampling. Validated and reliable questionnaires were used to assess the HFMD level of preventive practice and associated factors. Data were analysed by using SPSS version 28. Multivariate logistic regression was used to determine the predictors of good preventive practices. Results: The majority of respondents showed a good level of HFMD prevention practices (90.1%). Factors associated with HFMD preventive practice level were education level, history of child infected with HFMD and knowledge of HFMD (p<0.05). The predictors of a good level of preventive practices toward HFMD were tertiary education level (AOR = 8.28, 95% CI: 2.308, 20.154) and history of children infected with HFMD (AOR = 5.02, 95% CI: 1.192, 10.133). Conclusion: A high level of preventive practices among parents may contribute to the control and prevention at workplace child centres. Health promotion content may be improved by including parent's experience with HFMD. It is also useful to target health promotion towards parents with lower education levels and those who have never first-hand experience of a child with HFMD. [ABSTRACT FROM AUTHOR]

Background: Hand, foot, and mouth disease (HFMD) is a major public health issue in China while temperature and humidity are well-documented predictors. However, evidence on the combined effect of temperature and humidity is still limited. It also remains unclear whether such an effect could be modified by the enterovirus 71 (EV71) vaccination. Methods: Based on 320,042 reported HFMD cases during the summer months between 2012 and 2019, we conducted a study utilizing Distributed Lag Non-Linear Models (DLNM) and time-varying DLNM to examine how China's HFMD EV71 vaccine strategy would affect the correlation between meteorological conditions and HFMD risk. Results: The incidence of HFMD changed with the Discomfort Index in an arm-shaped form. The 14-day cumulative risk of HFMD exhibited a statistically significant increase during the period of 2017–2019 (following the implementation of the EV71 vaccine policy) compared to 2012–2016 (prior to the vaccine implementation). For the total population, the range of relative risk (RR) values for HFMD at the 75th, 90th, and 99th percentiles increased from 1.082–1.303 in 2012–2016 to 1.836–2.022 in 2017–2019. In the stratified analyses, Han Chinese areas show stronger relative growth, with RR values at the 75th, 90th, and 99th percentiles increased by 14.3%, 39.1%, and 134.4% post-vaccination, compared to increases of 22.7%, 41.6%, and 38.8% in minority areas. Similarly, boys showed greater increases (24.4%, 47.7%, 121.5%) compared to girls (8.1%, 28.1%, 58.3%). Additionally, the central Guizhou urban agglomeration displayed a tendency for stronger relative growth compared to other counties. Conclusions: Although the EV71 vaccine policy has been implemented, it hasn't effectively controlled the overall risk of HFMD. There's been a shift in the main viral subtypes, potentially altering population susceptibility and influencing HFMD occurrences. The modulating effects of vaccine intervention may also be influenced by factors such as race, sex, and economic level. Author summary: Hand, foot, and mouth disease (HFMD) is one of the most common childhood enteric infections worldwide and an important public health problem in China. In this study, we analyzed the relationships among HFMD cases, meteorological factors, and vaccine factors using time-varying distributed lag nonlinear models. We found that the susceptibility of the population may have changed after the implementation of the HFMD EV71 vaccine policy, altering the relationship between HFMD and meteorological factors. The modifying effects of vaccine interventions may be influenced by variables such as race, sex, and economic level. This provides valuable information for the prevention of the disease and policy decisions. [ABSTRACT FROM AUTHOR]

Foot-and-mouth disease virus (FMDV) belongs to the Picornaviridae family and is an important pathogen affecting cloven-hoof livestock. However, neither effective vaccines covering all serotypes nor specific antivirals against FMDV infections are currently available. In this study, we employed virtual screening to screen for secondary metabolite terpenoids targeting the RNA-dependent RNA polymerase (RdRp), or 3Dpol, of FMDV. Subsequently, we identified the potential antiviral activity of the 32 top-ranked terpenoids, revealing that continentalic acid, dehydroabietic acid (abietic diterpenoids), brusatol, bruceine D, and bruceine E (tetracyclic triterpenoids) significantly reduced cytopathic effects and viral infection in the terpenoid-treated, FMDV-infected BHK-21 cells in a dose-dependent manner, with nanomolar to low micromolar levels. The FMDV minigenome assay demonstrated that brusatol and bruceine D, in particular, effectively blocked FMDV 3Dpol activity, exhibiting IC50 values in the range of 0.37–0.39 µM and surpassing the efficacy of the antiviral drug control, ribavirin. Continentalic acid and bruceine E exhibited moderate inhibition of FMDV 3Dpol. The predicted protein–ligand interaction confirmed that these potential terpenoids interacted with the main catalytic and bystander residues of FMDV 3Dpol. Additionally, brusatol and bruceine D exhibited additive effects when combined with ribavirin. In conclusion, terpenoids from natural resources show promise for the development of anti-FMD agents. [ABSTRACT FROM AUTHOR]

Foot-and-mouth disease virus (FMDV) is a highly contagious virus that affects cloven-hoofed animals and causes severe economic losses in the livestock industry. Given that this high-risk pathogen has to be handled in a biosafety level (BSL)-3 facility for safety reasons and the limited availability of BSL-3 laboratories, experiments on FMDV call for more attention. Therefore, we aimed to develop an FMDV experimental model that can be handled in BSL-2 laboratories. The NanoBiT luciferase (Nano-luc) assay is a well-known assay for studying protein–protein interactions. To apply the NanoBiT split luciferase assay to the diagnosis and evaluation of FMD, we developed an inactivated HiBiT-tagged Asia1 Shamir FMDV (AS-HiBiT), a recombinant Asia1 shamir FMDV with HiBiT attached to the VP1 region of Asia1 shamir FMDV. In addition, we established LgBiT-expressing LF-BK cell lines, termed LgBit-LF-BK cells. It was confirmed that inactivated AS-HiBiT infected LgBiT-LF-BK cells and produced a luminescence signal by binding to the intracellular LgBiT of LgBiT-LF-BK cells. In addition, the luminescence signal became stronger as the number of LgBiT-LF-BK cells increased or the concentration of inactivated AS-HiBiT increased. Moreover, we confirmed that inactivated AS-HiBiT can detect seroconversion in sera positive for FMDV-neutralizing antibodies. This NanoBiT split luciferase assay system can be used for the diagnosis and evaluation of FMD and expanded to FMD-like virus models to facilitate the evaluation of FMDV vaccines and antibodies. [ABSTRACT FROM AUTHOR]

A cross-sectional study has been undertaken in El-Minia province to survey an outbreak of foot-and-mouth disease (FMD) in cattle and identify the associated risk factors. From November 2021 to October 2022, researchers collected 100 blood samples, ten tongue epithelium specimens, and saliva swabs from animals of various ages and sexes in different locations. Additionally, the animals were examined for FMD signs. The overall seroprevalence was tested via SNT, which was 67%. Tissue samples and swabs were isolated and examined using conventional RT-PCR for detection of the FMD serotype, revealing serotype A. Statistically, no significant variation (P > 0.05) was observed in the prevalence of FMD in relation to age, sex, season, or locality. The findings of this study indicated that the recent FMD outbreak has been caused by serotype A in the studied locations and that FMD is widespread in cattle populations in El-Minia province. These findings underline the necessity for immediate attention and future research to detect FMDV strains spreading in the region that aid in executing effective prevention strategies. [ABSTRACT FROM AUTHOR]

Foot-and-mouth disease (FMD) is a severe and extremely contagious viral disease. Cows, sheep, goats, deer, pigs, and other animals with divided hooves are among the animals infected by the FMD viruu, which is a member of the Picornaviridae family and genus Aphtho virus. There are seven different serotypes of this virus: Asia-1, SAT1, SAT2, SAT3, A, O, and C. Heat, ultraviolet light, pH values of 6.5 or higher, gamma radiation, chemicals, and disinfecting agents all inactivate the virus; however, it remains virtually stable at below- freezing temperatures for a prolonged amount of time. Animals affected by this disease develop vesicular lesions on their tongue, dental pad, gums, cheeks, hard and soft palates, lips, nostrils, muzzle, interdigital region (between the hoof), and a coronary band. Viral infections can spread through the respiratory tract or via the oral cavity. Clinical manifestations of FMD are used to diagnose the disease, along with laboratory and epidemiological investigations. Due to the high morbidity linked to outbreaks, difficulties in the local adoption of more advanced production techniques, limitations on trade between countries, and expenses related to the implementation of control measures, FMD results in significant economic losses. FMD can be controlled and prevented through immunization, restrictions on animal migration, physical segregation from wildlife, and clinical therapy. However, FMD demonstrated challenges to control because of its complicated epidemiological nature, poor diagnostic capacity, and lack of cross-immunity between strains. Investigation is consequently essential to progressing the creation of a multivalent and effective vaccination. [ABSTRACT FROM AUTHOR]

Introduction:Mumps is a highly contagious viral infection affecting the salivary glands, primarily caused by the mumps virus, a member of the Paramyxoviridae family. Despite being a self-limiting disease, mumps can lead to severe complications such as meningitis, encephalitis, orchitis, oophoritis, and permanent hearing loss. The introduction of the MMR vaccine has significantly reduced the incidence of mumps globally, but outbreaks continue to occur, particularly in areas with low vaccination coverage. In India, mumps is not a notifiable disease, and the vaccine is not included in the Universal Immunization Program (UIP), leading to underreporting and insufficient control measures. This study aims to analyze the recent trends in mumps cases in a paediatric population in Vijiyapura town of Bangalore Rural district and emphasize the need for including the mumps vaccine in the national immunization schedule. Methodology:This study was conducted at the Community Health Center (CHC) of Vijiyapura town in Bangalore Rural district. Cases were collected on an Paediatric Outpatient department (OPD) basis from children presenting with symptoms of mumps between March and May 2024. The World Health Organization (WHO) clinical case definition was used to diagnose mumps. Data were collected from all children who visited the OPD and met the clinical case definition. Results:A total of 18 cases of mumps were identified between March and May 2024. The age distribution ranged from 3 to 14 years, with a mean age of 7.1 years and a median age of 7 years. The majority of cases (77.8%) were male. Clinical presentations included fever (100%), constitutional symptoms such as headache and myalgia (80%), swelling of salivary glands (100%), with (27%) having unilateral parotid swelling and (73%) having bilateral parotid swelling. Cough and cold were observed in (80%) of the cases. Conclusion: The study highlights the increasing incidence of mumps in the paediatric population of Vijiyapura town of Bangalore Rural district, emphasizing the need for the inclusion of the mumps vaccine in the UIP. Strengthening the surveillance system and healthcare infrastructure is crucial for better management and control of mumps outbreaks. Collaboration among government agencies, healthcare workers, parents, and the community is essential to implement sustainable solutions and prevent future outbreaks. [ABSTRACT FROM AUTHOR]

Vaccination is a feasible approach for controlling foot-and-mouth disease (FMD). In FMD-free countries, vaccines are stored as a precautionary measure to control potential outbreaks. However, the challenge lies in pre-stocking optimal vaccines against the newly emerging strains. This study examined the potency of pre-stocked vaccines administered at elevated doses during emergencies. We vaccinated the cows with either a single or double trivalent vaccine dose containing two serotype O and one serotype A strains. Subsequently, vaccinated and unvaccinated cows were exposed to virulent strains of serotype O (O/JPN/2010; topotype Southeast Asia/Mya-98 lineage) or A (A/IRN/2016; topotype ASIA/G-VII lineage), which were genetically and antigenically distinct from the vaccine strains. Following challenge infections, all cows that received a single dose vaccination exhibited vesicular lesions with excreted viruses in the oral and nasal discharges. However, a substantial reduction was observed in the total clinical scores and virus titers in the sera and nasal discharges compared to those in the unvaccinated group. Cows receiving a doubled dose vaccination were completely protected from infection with O/JPN/2010 or demonstrated a significant decrease in viral shedding and clinical scores against A/IRN/2016. To note, vesicular lesions harbor significant amounts of viruses; thus, by mitigating their formation, viral transmission can be impeded, thereby slowing viral spread in the field. Furthermore, increasing the vaccine dose induced higher neutralizing antibody titers against heterologous strains. These findings suggest an alternative strategy for the effective management of future epidemics using pre-stocked vaccines. [ABSTRACT FROM AUTHOR]

Modern phylogeography aims at reconstructing the geographic movement of organisms based on their genomic sequences and spatial information. Phylogeographic approaches are often applied to pathogen sequences and therefore tend to neglect the possibility of recombination, which decouples the evolutionary and geographic histories of different parts of the genome. Genomic regions of recombining or reassorting pathogens often originate and evolve at different times and locations, which characterize their unique spatial histories. Measuring the extent of these differences requires new methods to compare geographic information on phylogenetic trees reconstructed from different parts of the genome. Here we develop for the first time a set of measures of phylogeographic incompatibility, aimed at detecting differences between geographical histories in terms of distances between phylogeographies. We study the effect of varying demography and recombination on phylogeographic incompatibilities using coalescent simulations. We further apply these measures to the evolutionary history of human and livestock pathogens, either reassorting or recombining, such as the Victoria and Yamagata lineages of influenza B and the O/Ind-2001 foot-and-mouth disease virus strain. Our results reveal diverse geographical paths of migration that characterize the origins and evolutionary histories of different viral genes and genomic segments. These incompatibility measures can be applied to any phylogeography, and more generally to any phylogeny where each tip has been assigned either a continuous or discrete "trait" independent of the sequence. We illustrate this flexibility with an analysis of the interplay between the phylogeography and phylolinguistics of Uralic-speaking human populations, hinting at patrilinear language transmission. [ABSTRACT FROM AUTHOR]

Foot-and-mouth disease virus (FMDV) cripples livestock by imparting devastating effects to economy. A good vaccine is the key to stopping it, but due to instability of 146S of FMDV, it is becoming difficult. This is bad because only 146S can fight against disease and its dissociation ultimately leads to decreased potency of vaccine. This study aimed to preserve the integrity of 146S in vaccine using different inactivators and preservatives. Foot-and-mouth Disease virus type 'O' was propagated on baby hamster kidney 21 cell lines and inactivated using formalin or binary ethylenimine (BEI). Size exclusion high performance liquid chromatography analysis revealed minimal 146S loss after double inactivation with formalin and BEI. This inactivated virus was further formulated into oil-based vaccine with sodium thiomersal or chloroform as a preservative. Our findings demonstrated that chloroform outperformed thiomersal in maintaining shelf life of vaccine. This claims that the combined approach of double inactivation with formalin and BEI followed by chloroform as preservative offered a promising strategy for developing efficacious FMDV. [ABSTRACT FROM AUTHOR]

Many viruses, including foot-and-mouth disease virus (FMDV), can promote the degradation of host proteins through macroautophagy/autophagy, thereby promoting viral replication. However, the regulatory mechanism between autophagy and innate immune responses is not fully understood during FMDV infection. Here, we found that the host GTPBP4/NOG1 (GTP binding protein 4) is a negative regulator of innate immune responses. GTPBP4 deficiency promotes the antiviral innate immune response, resulting in the ability of GTPBP4 to promote FMDV replication. Meanwhile, GTPBP4-deficient mice are more resistant to FMDV infection. To antagonize the host's antiviral immunity, FMDV structural protein VP1 promotes the expression of GTPBP4, and the 209th site of VP1 is responsible for this effect. Mechanically, FMDV VP1 promotes autophagy during virus infection and interacts with and degrades YTHDF2 (YTH N6-methyladenosine RNA binding protein F2) in an AKT-MTOR-dependent autophagy pathway, resulting in an increase in GTPBP4 mRNA and protein levels. Increased GTPBP4 inhibits IRF3 binding to the Ifnb/Ifn-β promoter, suppressing FMDV-induced type I interferon production. In conclusion, our study revealed an underlying mechanism of how VP1 negatively regulates innate immunity through the autophagy pathway, which would contribute to understanding the negative regulation of host innate immune responses and the function of GTPBP4 and YTHDF2 during FMDV infection. Abbreviation: 3-MA:3-methyladenine; ACTB: actin beta; ATG: autophagy related; ChIP:chromatin immunoprecipitation; CQ: chloroquine; DAPI:4',6-diamidino-2-phenylindole; dpi: days post-infection; EV71:enterovirus 71; FMDV: foot-and-mouth disease virus; GTPBP4/NOG1: GTPbinding protein 4; HIF1A: hypoxia inducible factor 1 subunit alpha;hpt:hours post-transfection; IFNB/IFN-β:interferon beta; IRF3: interferon regulatory factor 3; MAP1LC3/LC3:microtubule associated protein 1 light chain 3; MAVS: mitochondriaantiviral signaling protein; MOI: multiplicity of infection; MTOR:mechanistic target of rapamycin kinase; m6A: N(6)-methyladenosine;qPCR:quantitativePCR; SIRT3:sirtuin 3; SQSTM1/p62: sequestosome 1; STING1: stimulator ofinterferon response cGAMP interactor 1; siRNA: small interfering RNA;TBK1: TANK binding kinase 1; TCID50:50% tissue culture infectious doses; ULK1: unc-51 like autophagyactivating kinase 1; UTR: untranslated region; WT: wild type; YTHDF2:YTH N6-methyladenosine RNA binding protein F2 [ABSTRACT FROM AUTHOR]

Foot-and-mouth disease (FMD) outbreaks affecting Asiatic black bears (Ursus thibetanus) and a Malayan sun bear (Helarctos malayanus) were previously reported in 2011 in two housing facilities at a Vietnamese bear rescue centre. In this study, demographic data of all animals housed in the centre at the time of the outbreaks (n = 79) were collected. Blood samples drawn from 23 bears at different timepoints were tested for FMDV-specific antibodies targeting using a non-structural protein (NSP) ELISA and by virus neutralisation test (VNT). The relationship between seroconversion and clinical signs was explored and epidemic curves and transmission diagrams were generated for each outbreak, where FMD cases were defined as animals showing FMD clinical signs. Outbreak-specific attack rates were 18.75 and 77.77%, with corresponding basic reproduction numbers of 1.11 and 1.92, for the first and second outbreaks, respectively. Analyses of risk factors showed that after adjusting for sex there was strong evidence for a decrease in odds of showing clinical signs per year of age. All samples collected from bears before the outbreak tested negative to NSP and VNT. All cases tested positive to VNT following onset of clinical signs and remained positive during the rest of the follow up period, while only 6 out of 17 cases tested positive to NSP after developing clinical signs. Six animals without clinical signs were tested post outbreaks; five seroconverted using VNT and three animals were seropositive using NSP ELISA. This study provides initial epidemiological parameters of FMD in captive bears, showing that FMDV is easily spread between bears in close proximity and can cause clinical and subclinical disease, both of which appear to induce rapid and long-lasting immunity. [ABSTRACT FROM AUTHOR]

Background: Enterovirus 71 (EV-A71) causes Hand, Foot and Mouth Disease (HFMD) in children and has been associated with neurological complications. The molecular mechanisms involved in EV-A71 pathogenesis have remained elusive. Methods: A siRNA screen in EV-A71 infected-motor neurons was performed targeting 112 genes involved in intracellular membrane trafficking, followed by validation of the top four hits using deconvoluted siRNA. Downstream approaches including viral entry by-pass, intracellular viral genome quantification by qPCR, Western blot analyses, and Luciferase reporter assays allowed determine the stage of the infection cycle the top candidate, RAB11A was involved in. Proximity ligation assay, co-immunoprecipitation and multiplex confocal imaging were employed to study interactions between viral components and RAB11A. Dominant negative and constitutively active RAB11A constructs were used to determine the importance of the protein's GTPase activity during EV-A71 infection. Mass spectrometry and protein interaction analyses were employed for the identification of RAB11A's host interacting partners during infection. Results: Small GTPase RAB11A was identified as a novel pro-viral host factor during EV-A71 infection. RAB11A and RAB11B isoforms were interchangeably exploited by strains from major EV-A71 genogroups and by Coxsackievirus A16, another major causative agent of HFMD. We showed that RAB11A was not involved in viral entry, IRES-mediated protein translation, viral genome replication, and virus exit. RAB11A co-localized with replication organelles where it interacted with structural and non-structural viral components. Over-expression of dominant negative (S25N; GDP-bound) and constitutively active (Q70L; GTP-bound) RAB11A mutants had no effect on EV-A71 infection outcome, ruling out RAB11A's involvement in intracellular trafficking of viral or host components. Instead, decreased ratio of intracellular mature viral particles to viral RNA copies and increased VP0:VP2 ratio in siRAB11-treated cells supported a role in provirion maturation hallmarked by VP0 cleavage into VP2 and VP4. Finally, chaperones, not trafficking and transporter proteins, were found to be RAB11A's top interacting partners during EV-A71 infection. Among which, CCT8 subunit from the chaperone complex TRiC/CCT was further validated and shown to interact with viral structural proteins specifically, representing yet another novel pro-viral host factor during EV-A71 infection. Conclusions: This study describes a novel, unconventional role for RAB11A during viral infection where it participates in the complex process of virus morphogenesis by recruiting essential chaperone proteins. [ABSTRACT FROM AUTHOR]

Hand, foot, and mouth disease (HFMD) poses a significant public health threat primarily caused by four major enteroviruses: enterovirus 71 (EV71), coxsackieviruses A16, A10, and A6. Broadly protective immune responses are essential for complete protection against these major enteroviruses. In this study, we designed a new tetravalent immunogen for HFMD, validated it in silico , in vivo evaluated the immunogenicity of the DNA-based tetravalent vaccine in mice, and identified immunogenic B-cell and T-cell epitopes. A new tetravalent immunogen, VP1me, was designed based on the chimeric protein and epitope-based vaccine principles. It contains a complete EV71 VP1 protein and six reported neutralizing B-cell epitopes derived from the four major enteroviruses causing HFMD. In silico validation using multiple immunoinformatic tools indicated good attributes of the VP1me immunogen suitable for vaccine development. The VP1me-based DNA vaccine efficiently induced both humoral and cellular immune responses in BALB/cAJcl mice. A combination of in silico prediction and immunoassays enabled the identification of immunogenic linear B-cell and CD8 T-cell epitopes within the VP1me immunogen. Immunodominant linear B-cell epitopes were identified in six regions of VP1me, with one epitope located at the N-terminus of the VP1 protein (aa 9–23) regarded as a novel epitope. Interestingly, some B-cell epitopes could also induce the CD8 T-cell response, suggesting their dual functions in immune stimulation. These results lay the groundwork for further development of VP1me as a new vaccine candidate. [ABSTRACT FROM AUTHOR]

Background: Several factors, such as diverse serotypes, vaccination methods, weak biosecurity, and animal movements, contribute to recurrent Foot-and-Mouth Disease Virus (FMDV) outbreaks in Africa, establishing endemicity. These outbreaks cost over $2 billion annually, prompting a high-priority focus on FMDV vaccination. Despite extensive efforts, vaccine efficacy varies. This study aims to evaluate routine foot and mouth disease (FMD) vaccines in Africa via systematic review and meta-analysis. Methods: A systematic review and meta-analysis were carried out following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Meta-analysis was conducted to assess the efficacy of FMDV vaccination using the meta for package of R. Results: Vaccinated animals have roughly a 69.3% lower chance of FMDV infection compared to unvaccinated animals, as indicated by the pooled results from the random-effects model, which showed a risk ratio (RR) of 0.3073. There was a statistically significant heterogeneity (p < 0.05) across all of the included articles. Conclusion: Overall findings suggest that if properly planned and implemented, FMDV vaccination programs and strategies in Africa could help control the spread of the disease throughout the continent and beyond. [ABSTRACT FROM AUTHOR]

We aimed to characterize the change in the incidence of stillbirth (IS) in Japanese Black cattle during and after animal movement restrictions and suspended insemination because of a foot-and-mouth disease (FMD) outbreak in Miyazaki Prefecture in 2010. Calving data from 2006 to 2018 were collected from approximately 900 farms. Post-FMD period was divided into three based on the median IS per month (1.80%): period 1 (May 2011 to February 2013), period 2 (March 2013 to August 2015), and period 3 (September 2015 to December 2018). The ISs were similar during the Pre-FMD period and Post-FMD period 1, then substantially decreased during Post-FMD period 2 (p <.05), before returning to the value before the FMD outbreak period during Post-FMD period 3. Compared with the Pre-FMD period, Post-FMD period 1 was associated with a higher proportion of calvings by primiparous cows and Post-FMD period 2 was associated with a smaller number of calvings per month (p <.05). There were high ISs in primiparous cows during the Pre-FMD period, Post-FMD period 1, and Post-FMD period 3 (p <.05), but not during Post-FMD period 2. In summary, after the animal movement restrictions and suspended insemination introduced because of the FMD outbreak, the IS temporarily decreased and consequently returned to the pre-FMD level. [ABSTRACT FROM AUTHOR]

Infectious pancreatic necrosis virus (IPNV) causes economic losses with a highly variable mortality rate worldwide, especially in rainbow trout. The virus has a double-stranded bi-partite RNA genome designated segment A and B. New complete genome sequences of nine rainbow trout isolates from Turkey were determined and subjected to phylogenetic analysis, identifying all as genotype 5 (serotype Sp). A time-dependent change in the extended pathogenicity motif of VP2 from P217T221A247 (PTA) to PTE P217T221E247 over a period of 10 years was identified. A wider analysis of 99 IPNV sequences from Turkey and Iran revealed the emergence of the motif PTE from 2007 to 2017, inducing significant morbidity in fry by 2013. In fact, displacement of the PTA motif, by the PTE motif in IPNV isolates appeared to be connected to a production peak of rainbow trout in 2013. An additional CAI analysis provided more evidence, indicating that rainbow trout culture in Turkey has an influence on the evolution of IPNV. [ABSTRACT FROM AUTHOR]

Pig farming has become a strategically significant and economically important industry across the globe. It is also a potentially vulnerable sector due to challenges posed by transboundary diseases in which viral infections are at the forefront. Among the porcine viral diseases, African swine fever, classical swine fever, foot and mouth disease, porcine reproductive and respiratory syndrome, pseudorabies, swine influenza, and transmissible gastroenteritis are some of the diseases that cause substantial economic losses in the pig industry. It is a well-established fact that vaccination is undoubtedly the most effective strategy to control viral infections in animals. From the period of Jenner and Pasteur to the recent new-generation technology era, the development of vaccines has contributed significantly to reducing the burden of viral infections on animals and humans. Inactivated and modified live viral vaccines provide partial protection against key pathogens. However, there is a need to improve these vaccines to address emerging infections more comprehensively and ensure their safety. The recent reports on new-generation vaccines against swine viruses like DNA, viral-vector-based replicon, chimeric, peptide, plant-made, virus-like particle, and nanoparticle-based vaccines are very encouraging. The current review gathers comprehensive information on the available vaccines and the future perspectives on porcine viral vaccines. [ABSTRACT FROM AUTHOR]

Background and Aim: Foot-and-mouth disease (FMD) is a highly contagious viral disease that endangers livestock and the environment with significant economic consequences. This study aimed to validate the inactivation of the Indonesian isolate of foot-and-mouth disease virus (FMDV) with various formaldehyde concentration. Materials and Methods: The experiment started with FMDV being adapted on BHK-21 cells until cytopathic effects (CPE) appeared. The biological titer of the virus was determined using the 50% tissue culture infectious dose (TCID50) assay. The virus was inactivated by exposing the isolate to different formaldehyde (FA) concentrations (0.025%, 0.05%, 0.1%, and 0.2%) at 37 °C for 24 h, and residual infectivity was assessed using CPE scoring of reinoculated BHK-21 cells. Results: 72 h post-inoculation, the virulence of the FMDV isolate was indicated by complete CPE on BHK-21 monolayer cells, with a TCID50 value of 109/mL; CPE scoring did not signify significant differences (p < 0.05) among 0.025%, 0.05%, 0.1%, 0.2% FA, and the negative control. All treatment groups showed significant differences (p < 0.05) from the positive control (C+). FA concentrations inactivated the FMDV isolate under the given conditions. 0.025% and 0.05% FA continued to display CPE through the third passage, while 0.2% FA did not significantly differ from 0.1% FA (p > 0.05). 0.1% FA is the optimal concentration for safely and effectively inactivating FMDV. Conclusion: All of the formaldehyde concentrations can completely inactivate the FMDV isolate, with the most optimal and safe concentration being 0.1%. [ABSTRACT FROM AUTHOR]

Following the Irish War of Independence, 1919–21, and the ratification of the Anglo-Irish Treaty in 1922 the Irish Free State left the United Kingdom. Its leaders had been revolutionaries, whose explicit objective had been to overturn British authority in Ireland. Whilst the British ceded control of most of the island to the new state, an Anglo-Irish, Protestant, elite remained. The Royal Dublin Society (RDS) was the most prominent institution of it. As such, it might be expected that relations between the RDS and the new Irish state would be adverse. However, they were excellent. Drawing largely on the recently catalogued RDS archive, this article explains a seeming incongruity. It does so with general reference to the theme of agricultural development and specific reference to the agendas of the RDS and the new state; the role of key figures; the British foot-and-mouth disease crisis of the 1920s; and the response to partition. It also tests the academic discourse on what the Irish Revolution represented in socio-political terms, and the position of the former Protestant plutocracy in post-independence Ireland. [ABSTRACT FROM AUTHOR]

OBJECTIVE Foot-and-mouth disease (FMD) is a highly contagious disease in ruminants that causes significant economic losses worldwide. However, the prevalence of FMD virus (FMDV) in small ruminants has been overlooked in Pakistan. This study aimed to determine the prevalence of FMD in sheep and goats in the border area between Pakistan and Afghanistan. ANIMALS 800 sheep and goats belongs to age groups of 6 month to > 2 years. METHODS A total of 800 serum samples were collected from sheep (n = 424) and goats (n = 376) and subjected to structural protein (SP) and 3ABC non-SP (NSP) ELISAs for the detection of antibodies against SP and NSP of the FMDV. RESULTS For NSP, 340/800 (42.5%) of samples were positive, while SP analysis revealed that serotype O (44.5%) was the most common in sheep and goats, followed by Asia-1 (42%) and A (32%) serotypes. Sheep (39%; 95% CI, 34 to 44) had a higher (P < .05) prevalence of FMD than goats (46%; 95% CI, 41 to 51). Statistically significant (P < .05) differences in the seroprevalence of FMD-SP and FMD-NSPs were observed between various agencies (areas) of the study area. Risk factors such as age, sex, breed, season, flock size, body condition, animal movement, and production system were significantly (P < .05) associated with FMDV prevalence. CONCLUSIONS This study showed that FMD is highly prevalent in sheep and goats in the border areas of Pakistan and Afghanistan. Therefore, outbreak investigation teams should be arranged at the border level to develop FMD risk-based surveillance and control plans for small ruminants in order to mitigate infection risks. [ABSTRACT FROM AUTHOR]

Foot and mouth disease (FMD) is an infectious vesicular disease of cloven-hoofed animals caused by the FMD virus. It is acute, highly contagious, and has a lot of genetic diversity. The aim of this study was to confirm cases diagnosed in the field as FMD virus (FMDV) infection through identification and molecular characterization based on the amplification of the VP1 gene of FMDV to provide information about serotype, virus clustering, and additional molecular scientific data on FMDV circulating in Indonesia. The samples used in this study were Madura cattle and Ongole Grade cattle, which showed clinical signs of FMD. Twenty-six samples were collected from the vesicular fluid of blister epithelial cells (tongue, gum, and hard palate), oral, and nasal swabs. Those samples underwent a screening test using the real-time reverse transcription-polymerase chain reaction (RT-qPCR) method with a 3D gene target to detect FMDV infection. About 46.15% of samples (12/26) were detected as RT-qPCR positive for FMDV. Those positive results were then amplified by reverse transcription-polymerase chain reaction (RT-PCR) and sequenced using the Sanger sequencing technique targeting the VP1 gene fragment of the FMDV. The sequencing results were analyzed by the Molecular Evolutionary Genetics Analysis (MEGA) software X version, which includes assembly, alignment using ClustalW, amino acid prediction, genetic distance, and phylogenetic tree construction. The result showed that amino acid sequence variations were found in this gene, including at positions 96, 99, 129, 134, 138, 140, 156, 158, and 197, and no changes were found either at the critical amino acid sites at positions 144 (V), 148 (L), 154 (K), and 208 (P) or in the arginine-glycine-aspartic acid (RGD) motif at positions 145-147. Phylogenetic analysis indicated that FMD viruses detected in this study were identified as serotype "O", topotype "Middle East South Asia (ME-SA)", lineage "Ind-2001", and sub-lineage "e" (O/ME-SA/Ind-2001e), which have high homology to the VP1 gene (99-100%) between the viruses studied and the viruses found at the beginning of the FMD outbreak in Indonesia in 2022. [ABSTRACT FROM AUTHOR]

Lumpy skin disease (LSD) is one of the most important diseases causing great economic losses in live animals stock industry of affected countries. It is an infectious vector borne viral illness considered one of major trans-boundary animal diseases affecting cattle and Asian domestic buffaloes (Bubalus bubalis). The aim of the current review is to clarify the current status of LSD epidemiology and to throw light on the methods of LSD diagnosis, prevention, treatment and control. LSD is rarely fatal, characterised by nodules on the entire skin of the affected animals, and has a high morbidity rate. The disease has severe direct adverse effects on cattle production, milk yields and animal body condition from damage of hides, abortions, infertility and other indirect effects resulted from restriction of animal movements and trade. The first recorded outbreak was in Zambia in 1929. It is considered an endemic disease in African continent. First report of LSD in Egypt was in Suez Canal governorate in 1988. Diagnosis of LSD virus depends on the highly characteristic clinical signs in severely infected cases. In mild cases the diagnosis depends on the detection and isolation of the virus on different cell lines and on chorio-allantoic membranes of embryonated chicken eggs. Viral nucleic acid detection by molecular techniques as real time PCR is considered the test of priority because it is rapid, sensitive and quantitative. Prevention of the disease depends mainly on vaccination programmes for the entire cattle and buffalo populations, restriction of animals' movement inside the country and through country borders, controlling insect vectors, in addition to symptomatic treatment of infected animals. [ABSTRACT FROM AUTHOR]

Background: Herpes simplex virus-1, commonly known as oral herpes, is a highly contagious viral infection in humans. Various therapies and clinical management strategies have treated Herpes simplex virus-1 infection, but drug resistance is a concern, which has sparked an obsession with herpes simplex virus therapy. Therefore, interest in herbal medications with antiviral properties has increased. This research aimed to investigate the antiviral activity of pomegranate flower extracts on herpes simplex virus-1 type 1 in Vero cells under in vitro conditions. Material and Methods: This study evaluated the anti-herpetic effect of pomegranate flower extracts, and the plaque reduction assay was performed on Vero cells. For cytotoxicity determination of pomegranate flower extracts, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide was used. The total flavonoid and phenolic contents of three varieties of Punica granatum (P. granatum) were measured based on gallic acid (mg/g) and rutin equivalents (mg/g), respectively. Results: Pomegranate flower extracts had no cytotoxic impact at doses ranging from 80 to 140 µg/ml. Our study revealed that pomegranate flower extracts prevented the growth of viral plaques, and the IC50 values of three P. granatum species--pleniflora, Saveh Black Leather, and Sweet Alak--were 109.63, 131.24, and 128.87 µg/ml, respectively. Also, evaluation of total phenolic and flavonoid content showed that P. granatum var. pleniflora (Golnare farsi) had the highest total phenolic and flavonoid content (17.8 mg/g of gallic acid and 2.2 mg/g of rutin equivalents, respectively). Conclusion: The pomegranate flower extracts have an inhibitory impact on herpes simplex virus-1 and could be used as an anti-HSV-1 agent in further investigation. [ABSTRACT FROM AUTHOR]

Background: Food and mouth disease (FMD) is an endemic disease of cattle and other cloven hoofed animals. The objective of this study was to investigate the genetic characteristics and evolutionary relationships for the 2020 to 2021 field circulating Food and mouth disease virus (FMDV) obtained from reported outbreaks in different parts of Tanzania. Methods: The epithelial tissues were collected from lesions (oral, nasal, interdigital) of FMD suspect cases, stored and shipped to the laboratory for analysis. In the laboratory, the samples were prepared for nucleic acid extraction, FMDV detection, typing, sequencing, and phylogeny analysis. The construction of the phylogenetic trees was done by aligning current field strains nucleotide sequences with those from past studies stored in GenBank database. Results: The study identified three FMDV serotypes (A, O and, SAT1) to be circulating in the field as Africa Topotype G-I lineage, EA-2 Topotype, and Topotype I (NWZ) respectively. The identified field strains showed diverse scores of shared identity among current and past study strains. The generated nucleotide sequences from this study types O and SAT1 field strains were analysed categorically, and showed shared percent identities of 92.0-100.0% and 96.9-98.8% respectively. Conclusion: The sequencing and analysis of the VP1 coding region enhance FMDV knowledge on the genetic and evolutionary relationships existing among field strains, and commend for improved future strategies for effective national, regional and global FMD control measures. [ABSTRACT FROM AUTHOR]

Streptococcus agalactiae (group B streptococci, GBS) is responsible for severe infections in both neonates and adults. Currently, empiric antimicrobial therapy for sepsis and meningitis is the combined use of penicillin and gentamicin due to the enhanced bactericidal activity. However, high-level gentamicin resistance (HLGR) abrogates the synergism. The rate of HLGR was investigated within a dataset of 433 GBS strains collected from cases of invasive disease in both adults and neonates as well as from pregnant carriers. GBS isolates (n = 20, 4.6%) presented with HLGR (gentamicin MIC breakpoint >1024 mg/L) that was differently diffused between strains from adults or neonates (5.2% vs. 2.8%). Notably, 70% of HLGR GBS strains (14 isolates) were serotype IV. Serotype IV HLGR-GBS isolates were susceptible to all antibiotics tested, exhibited the alpha-C/HvgA/PI-2b virulence string, and belonged to sequence type 1010 (clonal complex (CC) 452). The mobile element that harbored the HLGR aac(6′)-aph(2)″ gene is a novel integrative and conjugative element (ICE) about 45 kb long, derived from GBS 515 ICE tRNALys. The clonal expansion of this HLGR hypervirulent serotype IV GBS CC452 sublineage may pose a threat to the management of infections caused by this strain type. [ABSTRACT FROM AUTHOR]