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1.
Vet Res ; 53(1): 63, 2022 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-35927724

RESUMO

Foot-and-mouth disease (FMD) is one of the most important livestock diseases restricting international trade. While African buffalo (Syncerus caffer) act as the main wildlife reservoir, viral and immune response dynamics during FMD virus acute infection have not been described before in this species. We used experimental needle inoculation and contact infections with three Southern African Territories serotypes to assess clinical, virological and immunological dynamics for thirty days post infection. Clinical FMD in the needle inoculated buffalo was mild and characterised by pyrexia. Despite the absence of generalised vesicles, all contact animals were readily infected with their respective serotypes within the first two to nine days after being mixed with needle challenged buffalo. Irrespective of the route of infection or serotype, there were positive associations between the viral loads in blood and the induction of host innate pro-inflammatory cytokines and acute phase proteins. Viral loads in blood and tonsil swabs were tightly correlated during the acute phase of the infection, however, viraemia significantly declined after a peak at four days post-infection (dpi), which correlated with the presence of detectable neutralising antibodies. In contrast, infectious virus was isolated in the tonsil swabs until the last sampling point (30 dpi) in most animals. The pattern of virus detection in serum and tonsil swabs was similar for all three serotypes in the direct challenged and contact challenged animals. We have demonstrated for the first time that African buffalo are indeed systemically affected by FMD virus and clinical FMD in buffalo is characterized by a transient pyrexia. Despite the lack of FMD lesions, infection of African buffalo was characterised by high viral loads in blood and oropharynx, rapid and strong host innate and adaptive immune responses and high transmissibility.


Assuntos
Vírus da Febre Aftosa , Febre Aftosa , Animais , Anticorpos Antivirais , Búfalos , Comércio , Febre/veterinária , Vírus da Febre Aftosa/fisiologia , Imunidade , Internacionalidade
2.
Arch Razi Inst ; 77(1): 37-44, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35891774

RESUMO

Foot-and-mouth disease (FMD) is an acute and highly contagious disease in livestock, such as cattle, sheep, and pigs, leading to a lot of economic losses. The current FMD vaccines formulated by inactivated whole-virus and adjuvant successfully reduce disease outbreaks in many regions of the world. Immunological studies on FMD viruses revealed that the dominant epitope in arising neutral antibody response is amino acid residues constructing the G-H loop, constituting a surface loop of the structural protein, termed VP1. Liposomes as one of the most well-known vehicles are considered an important carrier in vaccine development, and their function is used to encapsulate purified VP1 protein based on their size, charge, and lipid content. Accordingly, the VP1 protein was isolated from the FMD virus. This study aimed to compare four methods of VP1 protein encapsulation in the liposome and the extruding effect, as follows: 1) VP1 protein was dissolved in dimethyl sulfoxide and added to the lipid film hydrated by ethanol, 2) the lipid film was hydrated by VP1 protein with 7M urea, 3) the lipid film was hydrated by VP1 protein and freeze-thawed, and 4) the lipid film was hydrated by VP1 protein. The highest encapsulation efficiency was 91% in the second method which purified protein-containing urea. The VP1 protein in the prepared liposome (1, 2-dimyristoyl-sn-glycero-3-phosphocholine: 1, 2-dimyristoyl-sn-glycero-3-phosphocholine: cholesterol) released more than 90% of protein content after 240 h.


Assuntos
Doenças dos Bovinos , Vírus da Febre Aftosa , Febre Aftosa , Doenças dos Ovinos , Doenças dos Suínos , Vacinas Virais , Animais , Anticorpos Antivirais , Proteínas do Capsídeo , Bovinos , Doenças dos Bovinos/prevenção & controle , Febre Aftosa/prevenção & controle , Lipídeos , Lipossomos , Fosforilcolina , Ovinos , Suínos , Doenças dos Suínos/prevenção & controle , Ureia
3.
Viruses ; 14(8)2022 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-35893699

RESUMO

Foot and mouth disease (FMD) causes severe economic losses to the livestock industry of endemic countries, including Pakistan. Pakistan is part of the endemic pool 3 for foot and mouth disease viruses (FMDV), characterized by co-circulating O, A, and Asia 1 serotypes, as designated by the world reference laboratory for FMD (WRL-FMD). FMDV serotype A lineage ASIA/Iran-05 is widespread in buffalos and cattle populations and was first reported in Pakistan in 2006. This lineage has a high turnover, with as many as 10 sub-lineages reported from Pakistan over the years. In this study, we reconstructed the evolutionary, demographic, and spatial history of serotype A and one of its sub-lineages, A/ASIA/Iran-05/SIS-13, prevalent in Pakistan. We sequenced nearly complete genomes of three isolates belonging to sub-lineage A/ASIA/Iran-05/SIS-13. We estimated recombination patterns and natural selection acting on the serotype A genomes. Source and transmission routes in Pakistan were inferred, and the clustering pattern of isolates of the SIS-13 sub-lineage were mapped on a tree. We hereby report nearly complete genome sequences of isolates belonging to sub-lineage A/ASIA/Iran-05/SIS-13, along with purported recombinant genomes, and highlight that complete coding sequences can better elucidate the endemic history and evolutionary pressures acting on long-term co-circulating FMDV strains.


Assuntos
Vírus da Febre Aftosa , Febre Aftosa , Animais , Bovinos , Febre Aftosa/epidemiologia , Irã (Geográfico) , Paquistão/epidemiologia , Filogenia , Sorogrupo
4.
Braz J Biol ; 84: e263385, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35894355

RESUMO

Foot-and-mouth disease is responsible for severe economic losses to the livestock industry of Pakistan. This study aimed to use Swiss albino mice as a cost-effective experimental animal model to study different immunological and histopathological aspects of FMDV instead of natural targeted species like cattle. After isolation of field isolates FMDV on BHK-21 cell line, biological titer of the virus and mice infectious dose50 was calculated. Virus was injected in 45 Swiss albino mice (group A) through intraperitoneal route. The gross, histopathological and immunopathological lesions in heart, trachea and lungs were recorded at different day's intervals. Histopathologically, the heart showed congestion, hemorrhages and necrosis of cardiac muscles. Trachea showed deciliated epithelium and lungs showed hemorrhages, bronchial edema and alveolar emphysema. Immunohistochemical studies revealed the presence of virus in cardiac muscles, tracheal and bronchial epithelium and alveolar lumen. The findings evoked a thought that laboratory animals could be an alternative to large animals to meet budget limitations for further research on foot-and-mouth-disease.


Assuntos
Vírus da Febre Aftosa , Febre Aftosa , Animais , Bovinos , Camundongos , Paquistão
5.
Front Cell Infect Microbiol ; 12: 940906, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35873170

RESUMO

Foot-and-mouth disease virus (FMDV) could cause acute infection in host cells, or they could coexist with host cells to generate persistent infection. In persistent infection, the virus could survive for a long time in the host and could be transmitted between different host cells. In the case of FMDV-persistent infection cell line, there is a remarkable significant cellular heterogeneity in the FMDV-persistent infection cell line due to differences of viral load in the individual cells within the cell line. However, the mechanisms of FMDV-persistent infection are not well understood. It is now generally accepted that multiple factors contribute to the coevolution of viruses and cells during the course of persistent infection. The outcome would influence the development of persistent FMDV infection conjointly, reaching a state of equilibrium ultimately. Therefore, in order to elucidate the mechanism of cellular heterogeneity in FMDV-persistent infection cell line, single-cell sequencing was performed on BHK-Op, and pseudotime trajectory plot was draw through cell cluster. Based on the cell clusters, we predicted the development and progression of the FMDV-persistent infection. It could be well explained by the fact that, in BHK-Op cells, there are a fraction of infected cells and a fraction of virus-exposed but uninfected bystander cells. By further comparing the transcripts in cell clusters, we found that these genes were involved in changes in ribosome biogenesis, cell cycle, and intracellular signaling including the interferon signaling pathway and mitogen-activated protein kinase (MAPK) signaling pathway. Through comprehensive cross-tabulation analysis of differential expressed genes in various cluster of cells, we identified a high association of Fos, a downstream transcription factor of the MAPK/extracellular signal-regulated kinase (ERK) signaling pathway, with viral replication during the formation of FMDV-persistent infection. Through the further study of Fos, we found that downregulation of Fos facilitates viral clearance during FMDV-persistent infection. Upregulation of c-Raf, which is the upstream of the MAPK/ERK signaling pathway, could promote FMDV replication through downregulation of Fos. Our research is the first to provide insight into the mechanism of the formation FMDV-persistent infection through single-cell sequencing using persistent infection cell line. Pseudotime trajectory analysis was the first time to apply for FMDV-persistent infection cell line. Our work highlights the detailed overview of the evolution of FMDV-persistent infection. We also analyzed the differential expressed genes in the replication or elimination of FMDV within the host. We found that the MAPK/ERK signaling pathway and its downstream transcription factor Fos play an important role in FMDV-persistent infection.


Assuntos
Vírus da Febre Aftosa , Febre Aftosa , Animais , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Febre Aftosa/genética , Vírus da Febre Aftosa/genética , Infecção Persistente , Fatores de Transcrição/metabolismo , Replicação Viral/genética
6.
Vet Res ; 53(1): 56, 2022 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-35804412

RESUMO

Foot-and-mouth disease (FMD) remains a very serious barrier to agricultural development and the international trade of animals and animal products. Recently, serotype O has been the most prevalent FMDV serotype in China, and it has evolved into four different lineages: O/SEA/Mya-98, O/ME-SA/PanAsia, O/ME-SA/Ind-2001 and O/Cathay. PanAsia-2, belonging to the O/ME-SA topotype, is prevalent in neighbouring countries and poses the risk of cross-border spread in China. This study aimed to develop a promising vaccine candidate strain that can not only provide the best protection against all serotype O FMDVs circulating in China but also be used as an emergency vaccine for the prevention and control of transboundary incursion of PanAsia-2. Here, two chimeric FMDVs (rHN/TURVP1 and rHN/NXVP1) featuring substitution of VP1 genes of the O/TUR/5/2009 vaccine strain (PanAsia-2) and O/NXYCh/CHA/2018 epidemic strain (Mya98) were constructed and evaluated. The biological properties of the two chimeric FMDVs were similar to those of the wild-type (wt) virus despite slight differences in plaque sizes observed in BHK-21 cells. The structural protein-specific antibody titres induced by the rHN/TURVP1 and wt virus vaccines in pigs and cows were higher than those induced by the rHN/NXVP1 vaccine at 28-56 dpv. The vaccines prepared from the two chimeric viruses and wt virus all induced the production of protective cross-neutralizing antibodies against the viruses of the Mya-98, PanAsia and Ind-2001 lineages in pigs and cattle at 28 dpv; however, only the animals vaccinated with the rHN/TURVP1 vaccine produced a protective immune response to the field isolate of the Cathay lineage at 28 dpv, whereas the animals receiving the wt virus and the rHN/NXVP1 vaccines did not, although the wt virus and O/GXCX/CHA/2018 both belong to the Cathay topotype. This study will provide very useful information to help develop a potential vaccine candidate for the prevention and control of serotype O FMD in China.


Assuntos
Doenças dos Bovinos , Vírus da Febre Aftosa , Febre Aftosa , Vacinas Virais , Animais , Bovinos , Doenças dos Bovinos/prevenção & controle , Comércio , Febre Aftosa/epidemiologia , Vírus da Febre Aftosa/genética , Internacionalidade , Sorogrupo , Suínos
7.
Viruses ; 14(7)2022 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-35891349

RESUMO

Thailand is one of the countries where foot and mouth disease outbreaks have resulted in considerable economic losses. Forecasting is an important warning technique that can allow authorities to establish an FMD surveillance and control program. This study aimed to model and forecast the monthly number of FMD outbreak episodes (n-FMD episodes) in Thailand using the time-series methods, including seasonal autoregressive integrated moving average (SARIMA), error trend seasonality (ETS), neural network autoregression (NNAR), and Trigonometric Exponential smoothing state-space model with Box-Cox transformation, ARMA errors, Trend and Seasonal components (TBATS), and hybrid methods. These methods were applied to monthly n-FMD episodes (n = 1209) from January 2010 to December 2020. Results showed that the n-FMD episodes had a stable trend from 2010 to 2020, but they appeared to increase from 2014 to 2020. The outbreak episodes followed a seasonal pattern, with a predominant peak occurring from September to November annually. The single-technique methods yielded the best-fitting time-series models, including SARIMA(1,0,1)(0,1,1)12, NNAR(3,1,2)12,ETS(A,N,A), and TBATS(1,{0,0},0.8,{<12,5>}. Moreover, SARIMA-NNAR and NNAR-TBATS were the hybrid models that performed the best on the validation datasets. The models that incorporate seasonality and a non-linear trend performed better than others. The forecasts highlighted the rising trend of n-FMD episodes in Thailand, which shares borders with several FMD endemic countries in which cross-border trading of cattle is found common. Thus, control strategies and effective measures to prevent FMD outbreaks should be strengthened not only in Thailand but also in neighboring countries.


Assuntos
Doenças dos Bovinos , Febre Aftosa , Animais , Bovinos , Doenças dos Bovinos/epidemiologia , Surtos de Doenças/prevenção & controle , Surtos de Doenças/veterinária , Fazendas , Febre Aftosa/epidemiologia , Febre Aftosa/prevenção & controle , Incidência , Tailândia/epidemiologia
8.
Viruses ; 14(7)2022 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-35891476

RESUMO

Antibodies to the foot-and-mouth disease virus (FMDV) capsid induced by infection or vaccination can provide serotype-specific protection and be measured using virus neutralization tests and viral structural-protein (SP-)ELISAs. Separate tests are needed for each serotype, but cross-serotype reactions complicate serotyping. In this study, inter-serotypic responses were quantified for five SP-ELISA formats by testing 294 monovalent mainly bovine sera collected following infection, vaccination, or vaccination and infection with one of five serotypes of FMDV. Over half of the samples, representing all three immunization categories, scored positive for at least one heterologous serotype and some scored positive for all serotypes tested. A comparative approach to identifying the strongest reaction amongst serotypes O, A and Asia 1 improved the accuracy of serotyping to 73-100% depending on the serotype and test system, but this method will be undermined where animals have been infected and/or vaccinated with multiple FMDV serotypes. Preliminary studies with stabilized recombinant capsid antigens of serotypes O and A that do not expose internal epitopes showed reduced cross-reactivity, supporting the hypothesis that capsid integrity can affect the serotype-specificity of the SP-ELISAs. The residual cross-reactivity associated with capsid surface epitopes was consistent with the evidence of cross-serotype virus neutralization.


Assuntos
Vírus da Febre Aftosa , Febre Aftosa , Animais , Anticorpos Antivirais , Proteínas do Capsídeo/genética , Bovinos , Ensaio de Imunoadsorção Enzimática/métodos , Epitopos , Sorogrupo
9.
Viruses ; 14(7)2022 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-35891538

RESUMO

Foot-and-mouth disease (FMD) is an endemic disease in Ethiopia, although space-time cluster and monthly variation studies have never been assessed at national level. The current study aimed to identify the spatial and temporal distribution of FMD outbreaks in Ethiopia from national outbreak reports over a period of ten years from 1 January 2010 to 31 December 2019. To this end, a total of 376,762 cases and 1302 outbreaks from 704 districts were obtained from the Minister of Agriculture for analyses. In general, the dry periods, i.e., October to March, of the year were recorded as the peak outbreak periods, with the highest prevalence in March 2012. The monthly average and the outbreak trends over ten years show a decrease of outbreaks from 2010 to 2019. Decomposing the FMD outbreak data time series showed that once an outbreak erupted, it continued for up to five years. Only 12% of the reported outbreaks were assigned to a specific serotype. Within these outbreaks, the serotypes O, A, SAT-2, and SAT-1 were identified in decreasing order of prevalence, respectively. When a window of 50% for the maximum temporal/space cluster size was set, a total of seven FMD clusters were identified in space and time. The primary cluster with a radius of 380.95 km was identified in the southern part of Ethiopia, with a likelihood ratio of 7.67 (observed/expected cases). The third cluster, with a radius of 144.14 km, was identified in the northeastern part of the country, and had a likelihood ratio of 5.66. Clusters 1 and 3 occurred from January 2017 to December 2019. The second cluster that occurred had a radius of 294.82 km, a likelihood ratio of 6.20, and was located in the central and western parts of Ethiopia. The sixth cluster, with a radius of 36.04 km and a likelihood ratio of 20.60, was set in southern Tigray, bordering Afar. Clusters 2 and 6 occurred in the same period, from January 2014 to December 2016. The fourth cluster in northern Tigray had a calculated radius of 95.50 km and a likelihood ratio of 1.17. The seventh cluster occurred in the north-central Amhara region, with a radius of 97 km and a likelihood ratio of 1.16. Clusters 4 and 7 occurred between January 2010 and December 2013. The spatiotemporal and cluster analysis of the FMD outbreaks identified in the context of the current study are crucial in implementing control, prevention, and a prophylactic vaccination schedule. This study pointed out October to March as well as the main time of the year during which FMD outbreaks occur. The area that extends from the south to north, following the central highlands, is the main FMD outbreak area in Ethiopia.


Assuntos
Doenças dos Bovinos , Vírus da Febre Aftosa , Febre Aftosa , Animais , Bovinos , Doenças dos Bovinos/epidemiologia , Análise por Conglomerados , Surtos de Doenças , Etiópia/epidemiologia , Febre Aftosa/epidemiologia
10.
Vet Immunol Immunopathol ; 250: 110458, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35841772

RESUMO

A challenging but critical question is that new foot-and-mouth disease (FMD) vaccines should be to induce B cell memory to provide antibodies for long-term protection. The maintenance of B cell memory is dependent on long-lived plasma cells (LLPCs) and memory B cells. We developed a chimeric FMDV virus-like particles (FMDV-VLPs), fusing VP1-VP4 into HBcAg. In our study, we investigated if or how long B cell memory was induced by FMDV-VLPs in mice. The data showed that FMDV-VLPs can induce memory humoral responses with a high level of total IgG1, IgG2a, IgA, and FMDV-specific IgG antibodies in serum. The persistence of antibody levels in serum could depend on LLPCs. The proportion of LLPCs in CD19+ cells in bone marrow exhibited a dynamic trend with two peaks at 28 days post-immunization (dpi) and 72 dpi, respectively. Additionally, the proportion of memory B cells in CD19+ cells in the spleen increased significantly both at 7 days post primary immunization and at 7 days post -boost immunization. Of note, LLPCs together with memory B cells contribute to the production of FMDV-specific IgG and IgG1. The changes of LLPCs and memory B cells may be related to TNF-α, IL-6 and, CXCL12. Taken together, FMDV-VLPs could induce B cells memory responses. A further understanding of the mechanisms that FMDV-VLPs how we can manipulate the induction and maintenance of memory B cells and LLPCs will promote vaccine design and likely address several challenges to develop FMDV new vaccines in the future.


Assuntos
Vírus da Febre Aftosa , Febre Aftosa , Doenças dos Roedores , Vacinas de Partículas Semelhantes a Vírus , Vacinas Virais , Animais , Anticorpos Antivirais , Febre Aftosa/prevenção & controle , Imunoglobulina G , Camundongos , Camundongos Endogâmicos BALB C
11.
Microb Pathog ; 169: 105650, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35764187

RESUMO

Foot-and-mouth disease (FMD) is an extremely contagious and economically devastating viral disease of cloven-hoofed domestic and wildlife animals. The disease is endemic in India and other developing countries of the world. The disease is mainly characterized by the presence of vesicular lesions and "tigroid heart" in calves. The current report describes the novel pathologic findings along with the distribution of FMDV antigens in brain of young calves naturally infected with FMDV. The carcasses of 37 calves suspected to have died from FMD were presented for postmortem investigation. Out of 37 dead calves, 10 calves showed the clinical signs of neurological abnormalities like opisthotonos, muscle twitching and tremor in hind limbs, stiffening of the neck followed by death. Microscopically, the meninges were congested, hemorrhagic, and infiltrated with mononuclear cells. The various sub anatomical sites of the brain showed the varying degrees of vascular changes, perivascular cuffing, focal to diffuse gliosis as well as degeneration and neuronal necrosis, indicating the nonsuppurative encephalitis. The immunolabeling of FMDV antigen was demonstrated in the neurons, inflammatory cells, and microglial cells besides its typical locations. The neurons of the brain also showed strong immunopositivity for caspase-3, caspase-9 and p53 and negative for Bcl-2 and apoptosis-inducing factor (AIF) by both immunohistochemistry and western blotting indicating the role of caspase mediated intrinsic, and p53 dependent apoptotic pathway. Further, the TUNEL assay also confirmed the apoptosis in the neurons and glial cells of the brain of naturally infected calves. This study in calves establishes a basis for resemblance to other members of Picornaviruses, such as Enterovirus 71 and Coxsackievirus of humans and showing the neuropathological alterations along with the distribution of FMDV antigens associated with apoptosis in younger calves.


Assuntos
Doenças dos Bovinos , Vírus da Febre Aftosa , Febre Aftosa , Animais , Encéfalo , Bovinos , Doenças dos Bovinos/diagnóstico , Humanos , Proteína Supressora de Tumor p53
12.
Viruses ; 14(6)2022 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-35746633

RESUMO

Foot-and-mouth disease is an economically devastating disease of livestock caused by foot-and-mouth disease virus (FMDV). Vaccination is the most effective control measure in place to limit the spread of the disease; however, the success of vaccination campaigns is hampered by the antigenic diversity of FMDV and the rapid rate at which new strains emerge that escape pre-existing immunity. FMDV has seven distinct serotypes, and within each serotype are multiple strains that often induce little cross-protective immunity. The diversity of FMDV is a consequence of the high error rate of the RNA-dependent RNA polymerase, accompanied by extensive recombination between genomes during co-infection. Since multiple serotypes and strains co-circulate in regions where FMDV is endemic, co-infection is common, providing the conditions for recombination, and also for other events such as trans-encapsidation in which the genome of one virus is packaged into the capsid of the co-infecting virus. Here, we demonstrate that the co-infection of cells with two FMDVs of different serotypes results in trans-encapsidation of both viral genomes. Crucially, this facilitates the infection of new cells in the presence of neutralizing antibodies that recognize the capsid that is encoded by the packaged genome.


Assuntos
Coinfecção , Vírus da Febre Aftosa , Febre Aftosa , Animais , Anticorpos Neutralizantes/genética , Anticorpos Antivirais , Proteínas do Capsídeo/genética , Vírus da Febre Aftosa/genética , Sorogrupo
13.
PLoS Pathog ; 18(6): e1010589, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35666744

RESUMO

Non-coding regions of viral RNA (vRNA) genomes are critically important in the regulation of gene expression. In particular, pseudoknot (PK) structures, which are present in a wide range of RNA molecules, have a variety of roles. The 5' untranslated region (5' UTR) of foot-and-mouth disease virus (FMDV) vRNA is considerably longer than in other viruses from the picornavirus family and consists of a number of distinctive structural motifs that includes multiple (2, 3 or 4 depending on the virus strain) putative PKs linked in tandem. The role(s) of the PKs in the FMDV infection are not fully understood. Here, using bioinformatics, sub-genomic replicons and recombinant viruses we have investigated the structural conservation and importance of the PKs in the FMDV lifecycle. Our results show that despite the conservation of two or more PKs across all FMDVs, a replicon lacking PKs was replication competent, albeit at reduced levels. Furthermore, in competition experiments, GFP FMDV replicons with less than two (0 or 1) PK structures were outcompeted by a mCherry FMDV wt replicon that had 4 PKs, whereas GFP replicons with 2 or 4 PKs were not. This apparent replicative advantage offered by the additional PKs correlates with the maintenance of at least two PKs in the genomes of FMDV field isolates. Despite a replicon lacking any PKs retaining the ability to replicate, viruses completely lacking PK were not viable and at least one PK was essential for recovery of infections virus, suggesting a role for the PKs in virion assembly. Thus, our study points to roles for the PKs in both vRNA replication and virion assembly, thereby improving understanding the molecular biology of FMDV replication and the wider roles of PK in RNA functions.


Assuntos
Vírus da Febre Aftosa , Febre Aftosa , Regiões 5' não Traduzidas , Animais , Vírus de DNA , Febre Aftosa/genética , Vírus da Febre Aftosa/genética , Genoma Viral , RNA Viral/química , Replicação Viral/genética
15.
Prev Vet Med ; 205: 105695, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35772240

RESUMO

In 2021, the 88th General Session of the World Assembly of National Delegates to the World Organisation for Animal Health (OIE) recognized the estates of Acre, Paraná, the Rio Grande do Sul, and Rondônia as being free of foot-and-mouth disease (FMD) without vaccination. The certification was also extended to some cities in Amazonas and Mato Grosso. The new national strategic plan for 2026, which focuses on creating and maintaining sustainable conditions to expand FMD-free zones without vaccination, imposes new challenges and requires continuous evaluation of the FMD surveillance system. The objective of this research was to evaluate the FMD surveillance system in Brazil using quantitative models through Bayesian network approaches. The research was conducted using the Continental Surveillance and Information System (SivCont) database for Official Veterinary Services in Brazil, which refers to notified vesicular syndromes. The data on states, reported diseases, source of notification, disease confirmation, and timeliness (TL in days) of the delay by owners in notifying (TL.1) after a suspected case of the disease, and the response of Brazilian Veterinary Services after being notified (TL.2), were analysed. The collected data were analysed using Bayesian networks. It was observed that diseases with symptoms identical to FMD are the most notified events. TL.1 was long (mean of 18.96, CI: 18.33-19.59), and a low number of notifications was observed throughout the study period, which increases the chances of disseminating FMD in the population. Meanwhile, TL.2 suggests appropriate effectiveness of the Veterinary Services responding to suspected cases of FMD with interventions in less than 24 h (mean of 1, CI: 0.68-1.31). This study evaluated the performance of Brazilian Veterinary Services facing the report of vesicular diseases in the period 2004-2018. The results can help the states improve the surveillance system and the transition to the vaccination stop. Furthermore, the analytical method presented in the paper could serve as a model for other countries to evaluate the effectiveness of FMD surveillance systems.


Assuntos
Vírus da Febre Aftosa , Febre Aftosa , Animais , Teorema de Bayes , Brasil/epidemiologia , Surtos de Doenças/veterinária , Febre Aftosa/epidemiologia , Febre Aftosa/prevenção & controle , Saúde Global , Vacinação/veterinária
16.
ACS Appl Bio Mater ; 5(6): 3095-3106, 2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-35679606

RESUMO

Foot-and-mouth disease (FMD), a serious, fast-spreading, and virulent disease, has led to huge economic losses to people all over the world. Vaccines are the most effective way to control FMD. However, the weak immunogenicity of inactivated FMD virus (FMDV) requires the addition of adjuvants to enhance the immune effectiveness of the vaccines. Herein, we formulated and fabricated biodegradable dendritic mesoporous tetrasulfide-doped organosilica nanoparticles SOMSN with imiquimod complex (SOMSN-IMQ) and used it as a platform for FMD vaccine delivery and as an adjuvant. SOMSN-IMQ demonstrated excellent stability for 6 months when stored in PBS, while it could be completely degraded within 42 days in SBF at room temperature. Biosafety experiments such as cell toxicity, hemolysis, and histology indicated that the as-prepared SOMSN-IMQ showed nontoxicity and good biocompatibility. Furthermore, SOMSN-IMQ exhibited a maximum adsorption capacity of 1000 µg/mg for inactivated FMDV antigens. Our results showed that SOMSN-IMQ can be effectively engulfed by RAW264.7 cells in a dose-dependent manner. After immunization, SOMSN-IMQ@FMDV can elicit persistent higher antibody levels, higher IgG2a/IgG1 ratio, and cytokine expression, which indicated that SOMSN-IMQ@FMDV triggered superior humoral and cellular immune responses. Moreover, SOMSN-IMQ could provoke maturation and activation of dendritic cells in lymph nodes (LDCs) as well as the proliferation of lymphocytes in vivo. Thus, SOMSN-IMQ could promote effective and potent immunity and provide a promising adjuvant platform for FMDV vaccination with acceptable safety.


Assuntos
Vírus da Febre Aftosa , Febre Aftosa , Vacinas Virais , Adjuvantes Imunológicos/farmacologia , Adjuvantes Farmacêuticos , Animais , Anticorpos Antivirais , Febre Aftosa/prevenção & controle , Humanos , Imiquimode/farmacologia , Imunoglobulina G , Camundongos
17.
Trop Anim Health Prod ; 54(4): 215, 2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-35723776

RESUMO

Foot and mouth disease (FMD) is a highly contagious transboundary disease of cloven-hoofed animals. In Iran, the disease is endemic with outbreaks occurring throughout the year. Mass vaccination of domestic ruminants has been adopted as a preventive strategy. A study was conducted to evaluate the effectiveness of currently in use FMD vaccines using official disease surveillance data. Surveillance data of FMD outbreaks and vaccination in cattle farms from January 2017 to March 2019 was obtained from the Iranian Veterinary Organization (IVO). A case-control study comprising 190 laboratory-confirmed cases and 380 randomly selected controls, frequency-matched by location and production type, was performed to estimate vaccine effectiveness (VE) of vaccines in industrial and semi-industrial farms. Multivariable logistic regression was used to estimate odds ratios based on brand of vaccine, time since vaccination, and within-farm vaccination coverage. A total of 2297 outbreaks occurred during the study period with majority (75%) reported from village epi-units. Only 38% of industrial and semi-industrial farms recorded vaccination during the studied period. Vaccination was effective against clinical disease with the highest VE observed in farms vaccinated with commercial vaccine brand A (VE = 0.90%, 95% CI 0.79-0.96), vaccinating > 94% of herd population (VE = 0.77%, 95%CI 0.54-0.98) and in < 35 days after vaccination (VE = 0.56%, 95% CI 0.04-0.8). The current high-potency vaccines confer medium protection in investigated cattle farms. The high occurrence of the disease in village epi-units and low coverage of vaccination in industrial and semi-industrial farms will contribute to maintenance and circulation of the virus in the susceptible population.


Assuntos
Doenças dos Bovinos , Vírus da Febre Aftosa , Febre Aftosa , Vacinas Virais , Animais , Estudos de Casos e Controles , Bovinos , Doenças dos Bovinos/epidemiologia , Doenças dos Bovinos/prevenção & controle , Surtos de Doenças/prevenção & controle , Surtos de Doenças/veterinária , Febre Aftosa/epidemiologia , Febre Aftosa/prevenção & controle , Irã (Geográfico)/epidemiologia , Vacinação/veterinária
18.
J Virol ; 96(12): e0052822, 2022 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-35604219

RESUMO

Foot-and-mouth disease (FMD) is an acute contagious disease that affects cloven-hoofed animals and has severe global economic consequences. FMD is most commonly controlled by vaccination. Currently available commercial FMD vaccines contain chemically inactivated whole viruses, which are thought to be slow acting as they are effective only 4 to 7 days following vaccination. Hence, the development of a novel rapid vaccine or alternative measures, such as antiviral agents or the combination of vaccines and antiviral agents for prompt FMD virus (FMDV) outbreak containment, is desirable. Here, we constructed a recombinant baculovirus (BacMam) expressing consensus porcine interferon alpha (IFN-α) that has three additional N-glycosylation sites driven by a cytomegalovirus immediate early (CMV-IE) promoter (Bac-Con3N IFN-α) for protein expression in mammalian cells. Bac-Con3N IFN-α expressing highly glycosylated porcine IFN-α protein increased the duration of antiviral effects. We evaluated the antiviral effects of Bac-Con3N IFN-α in swine cells and mice and observed sustained antiviral effects in pig serum; additionally, Bac-Con3N IFN-α exhibited sustained antiviral effects in vivo as well as adjuvant effects in combination with an inactivated FMD vaccine. Pigs injected with a combination of Bac-Con3N IFN-α and the inactivated FMD vaccine were protected against FMDV at 1, 3, and 7 days postvaccination. Furthermore, we observed that in combination with the inactivated FMD vaccine, Bac-Con3N IFN-α increased neutralizing antibody levels in mice and pigs. Therefore, we suggest that Bac-Con3N IFN-α is a strong potential antiviral and adjuvant candidate for use in combination with inactivated FMD vaccines to protect pigs against FMDV. IMPORTANCE Early inhibition of foot-and-mouth disease (FMD) virus (FMDV) replication in pigs is highly desirable as FMDV transmission and shedding rates are higher in pigs than in cattle. However, commercial FMD vaccines require at least 4 to 7 days postvaccination (dpv) for protection, and animals are vulnerable to heterologous viruses before acquiring high antibody levels after the second vaccination. Therefore, the development of antiviral agents for use in combination with FMD vaccines is essential. We developed a novel antiviral and immunostimulant, Bac-Con3N IFN-α, which is a modified porcine IFN-α-expressing recombinant baculovirus, to improve IFN stability and allow its direct delivery to animals. We present a promising candidate for use in combination with inactivated FMD vaccines as pigs applied to the strategy had early protection against FMDV at 1 to 7 dpv, and their neutralizing antibody levels were higher than those in pigs administered the vaccine only.


Assuntos
Vírus da Febre Aftosa , Febre Aftosa , Interferon-alfa , Vacinas Virais , Adjuvantes Imunológicos/farmacologia , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais , Antivirais/farmacologia , Baculoviridae , Febre Aftosa/imunologia , Febre Aftosa/prevenção & controle , Interferon-alfa/farmacologia , Camundongos , Suínos , Vacinas de Produtos Inativados
19.
J Virol Methods ; 305: 114539, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35523370

RESUMO

Epithelial tissue or vesicular fluid from an unruptured or recently ruptured vesicle is the sample of choice for confirmatory laboratory diagnosis of foot-and-mouth disease (FMD). However, in 'FMD-free' countries the transport and downstream processing of such samples from potentially infected animals present a biosafety risk, particularly during heightened surveillance, potentially involving decentralised testing in laboratories without adequate biocontainment facilities. In such circumstances, rapid inactivation of virus, if present, prior to transport becomes a necessity, while still maintaining the integrity of diagnostic analytes. Tongue epithelium collected from cattle infected with FMD virus (FMDV) of serotype O (O/ALG/3/2014 - Lineage O/ME-SA/Ind-2001d) or A (A/IRN/22/2015 - Lineage A/ASIA/G-VII) was incubated in the PAXGene Tissue System Fixative (pH 4) and Stabiliser (pH 6.5) components respectively, in McIlvaine's citrate-phosphate buffer (pH 2.6) or in phosphate-buffered saline (PBS, pH 7.4) at room temperature for 2, 6, 24 or 48 h. Following incubation, tissues were homogenised and tested by virus isolation and titration using LFBKαVß6 cells. The integrity of FMD viral RNA was assessed by RT-qPCR (3Dpol coding region), Sanger sequencing of the VP1 region and transfection of LFBKαVß6 cells to recover infectious virus. Viable virus could be recovered from samples incubated in PBS for at least 48 h. The PAXgene Tissue System Stabiliser component yielded variable results dependent on virus serotype, requiring at least 6 h of incubation to inactivate A/IRN/22/2015 in most samples, whereas the Fixative component required up to 2 h in some samples. McIlvaine's citrate-phosphate buffer rapidly inactivated both viruses within 2 h of incubation. There was no demonstrable degradation of FMD viral RNA resulting from incubation in any of the buffers for up to 48 h, as assessed by RT-qPCR, and 24 h by sequencing and transfection to recover infectious virus. McIlvaine's citrate-phosphate buffer (pH 2.6) is easy to prepare, inexpensive and inactivates serotype A and O FMDV in epithelial tissue within 2 h, while maintaining RNA integrity for downstream diagnostic processes and virus characterisation.


Assuntos
Vírus da Febre Aftosa , Febre Aftosa , Animais , Bovinos , Citratos , Epitélio , Fixadores , Vírus da Febre Aftosa/genética , Fosfatos , RNA Viral/genética , Sorogrupo , Língua
20.
Viruses ; 14(5)2022 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-35632639

RESUMO

African buffalo are the natural reservoirs of the SAT serotypes of foot-and-mouth disease virus (FMDV) in sub-Saharan Africa. Most buffalo are exposed to multiple FMDV serotypes early in life, and a proportion of them become persistently infected carriers. Understanding the genetic diversity and evolution of FMDV in carrier animals is critical to elucidate how FMDV persists in buffalo populations. In this study, we obtained oropharyngeal (OPF) fluid from naturally infected African buffalo, and characterized the genetic diversity of FMDV. Out of 54 FMDV-positive OPF, 5 were co-infected with SAT1 and SAT2 serotypes. From the five co-infected buffalo, we obtained eighty-nine plaque-purified isolates. Isolates obtained directly from OPF and plaque purification were sequenced using next-generation sequencing (NGS). Phylogenetic analyses of the sequences obtained from recombination-free protein-coding regions revealed a discrepancy in the topology of capsid proteins and non-structural proteins. Despite the high divergence in the capsid phylogeny between SAT1 and SAT2 serotypes, viruses from different serotypes that were collected from the same host had a high genetic similarity in non-structural protein-coding regions P2 and P3, suggesting interserotypic recombination. In two of the SAT1 and SAT2 co-infected buffalo identified at the first passage of viral isolation, the plaque-derived SAT2 genomes were distinctly grouped in two different genotypes. These genotypes were not initially detected with the NGS from the first passage (non-purified) virus isolation sample. In one animal with two SAT2 haplotypes, one plaque-derived chimeric sequence was found. These findings demonstrate within-host evolution through recombination and point mutation contributing to broad viral diversity in the wildlife reservoir. These mechanisms may be critical to FMDV persistence at the individual animal and population levels, and may contribute to the emergence of new viruses that have the ability to spill-over to livestock and other wildlife species.


Assuntos
Coinfecção , Vírus da Febre Aftosa , Febre Aftosa , Animais , Animais Selvagens , Búfalos , Proteínas do Capsídeo/genética , Coinfecção/veterinária , Febre Aftosa/epidemiologia , Quênia , Filogenia , Sorogrupo
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