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PubMed2026

Genome-wide CRISPR screen identifies RNF24 as a critical host factor for foot-and-mouth disease virus entry.

BACKGROUND: Foot-and-mouth disease virus (FMDV) causes substantial economic losses in global livestock production; however, the key host factors supporting its early infection process remain poorly characterized. METHODS: In this study, we performed an unbiased genome-wide CRISPR/Cas9 knockout screening using porcine cells to screen and identify host factors involved in FMDV infection. RESULTS: We identified that the E3 ubiquitin ligase RNF24 supports efficient FMDV entry. RNF24 depletion inhibits viral entry and replication, whereas its overexpression enhances viral infectivity. Mechanistically, RNF24 preferentially promotes K27-linked non-degradative polyubiquitination of leupaxin (LPXN) at lysine 162, driving LPXN's trafficking to the plasma membrane. At the membrane, LPXN assembles a ternary integrin-LPXN-VP1 complex that strengthens virus-receptor interactions and promotes viral adsorption and entry. Disruption of this ubiquitination event via the LPXN K162R mutation impairs complex formation and compromises viral entry. CONCLUSION: Together, our study reveals a ubiquitin-dependent RNF24-LPXN regulatory axis that supports FMDV entry, highlights the role of non-degradative ubiquitination in viral pathogenesis, and proposes this interface as a potential target for antiviral intervention.

CRISPR screening↗
PubMed2003

The history of research in foot-and-mouth disease.

The history of research in foot-and-mouth disease falls into several distinct areas. In this short chapter I have highlighted what I consider to be the significant advances in our knowledge of the disease and its causal agent. 1. Loeffler and Frosch's landmark description in 1898 that the disease is caused by a filterable agent, the first observation that an animal disease could be caused by a virus. 2. The search for experimental laboratory animals, culminating in the demonstration by Waldmann and Pape of the susceptibility of the guinea pig in 1920 and the suckling mouse by Skinner in 1951. 3. The discovery of three distinct serotypes O, A and C in the 1920s by Vallée and Carré in France and by Waldmann in Germany, and the subsequent recognition in the 1940s and 1950s by the Pirbright group of the three Southern African Territory Types SAT 1-3, and Asia 1. 4. The development of in vitro techniques for the growth of the virus which have been crucial for the large-scale production of vaccines and for the accurate assay of virus infectivity. Early work by Hecke and the Maitlands in the early 1930s, followed by the crucial demonstration by Frenkel in 1947 that large amounts of the virus could be produced in surviving tongue epithelium, formed the basis for the vaccination programmes initiated in Europe in the 1950s. The subsequent development of cell lines has brought a remarkable degree of sophistication to the study of virus growth. 5. The impact of molecular studies on the structure of the virus and its mode of replication which have led to practical applications such as an in vitro test for vaccine potency, rapid diagnosis methods, and international epidemiological surveys. In addition, they have provided the means to design molecular vaccines.

Animals↗
PubMed1989

Biochemical and haematological evidence of endotoxic shock in gnotobiotic lambs with watery mouth disease.

Eight gnotobiotic lambs deprived of colostrum were infected by mouth when two hours old with nonenterotoxigenic strains of Escherichia coli. All developed clinical signs of watery mouth disease and seven died within 24 hours. The mean concentrations of several blood constituents were determined in samples taken at intervals until 24 hours after infection in infected lambs and in four control lambs. The biochemical and haematological changes observed in the lambs developing watery mouth disease were those characteristic of endotoxic shock.

Animals↗
PubMed2001

Eradication of foot and mouth disease in Japan.

An outbreak of foot and mouth disease (FMD) was recorded in Japan in the spring of 2000, the first for ninety-two years. Between 25 March and 11 May, four farms were infected. However, the disease was eradicated without resorting to vaccination, through a campaign of culling, movement control of cloven-hoofed animals in areas surrounding infected premises, and intensive clinical and serological surveillance. Japan regained FMD-free status by the end of September 2000. The authors describe the nature of the outbreaks, the eradication measures implemented, and the clinical and serological surveillance methods used. The possible sources of infection are also examined. Finally, the direct and indirect economic losses are presented.

Animals↗
PubMed2006

Use and abuse of mathematical models: an illustration from the 2001 foot and mouth disease epidemic in the United Kingdom.

Foot and mouth disease (FMD) is a major threat, not only to countries whose economies rely on agricultural exports, but also to industrialised countries that maintain a healthy domestic livestock industry by eliminating major infectious diseases from their livestock populations. Traditional methods of controlling diseases such as FMD require the rapid detection and slaughter of infected animals, and any susceptible animals with which they may have been in contact, either directly or indirectly. During the 2001 epidemic of FMD in the United Kingdom (UK), this approach was supplemented by a culling policy driven by unvalidated predictive models. The epidemic and its control resulted in the death of approximately ten million animals, public disgust with the magnitude of the slaughter, and political resolve to adopt alternative options, notably including vaccination, to control any future epidemics. The UK experience provides a salutary warning of how models can be abused in the interests of scientific opportunism.

Animal Welfare↗
PubMed2002

Control of foot and mouth disease: the experience of the Americas.

Foot and mouth disease (FMD) was first recognised in South America in 1870, almost simultaneously in the province of Buenos Aires (Argentina), in the central region of Chile, in Uruguay, in southern Brazil and coincidentally, on the northeastern coast of the United States of America. The epidemiology of the disease was unknown and no government action was taken following the initial outbreaks. This resulted in the disease spreading to other areas of Chile, as well as to Peru, Bolivia and Paraguay, reaching Venezuela and Colombia in the 1950s, and Ecuador in 1961. The entire continent was affected in the 1960s when national FMD control programmes were initiated, with the exception of Guyana, Surinam, French Guiana and Patagonia. In the 1970s, steps were taken to implement a regional control and eradication strategy in view of the impact of production and trade on the persistence of the virus. The Plan Hemisférico de Erradicación de la Fiebre Aftosa (PHEFA: Hemispheric FMD Eradication Plan), public- and private-sector policies, new diagnostic tools, the oil-adjuvanted FMD vaccine and regional strategies played a part in improving the epidemiological situation during the 1990s. A setback was encountered in 2000 and 2001, with outbreaks due to virus types A and 0 recorded in Argentina, Uruguay and Brazil.

Animals↗
PubMed2002

Foot and mouth disease: the future of vaccine banks.

The authors briefly review the history of vaccine banks for foot and mouth disease, their current location and their constituent serotypes and strains, together with the occasions on which they have been activated. Experimental studies on emergency vaccines are summarised and areas identified for further investigation. The future of such banks is considered, including the principal strengths and weaknesses of existing banks, and suggestions are made for potential improvements. The fact that the banks have been activated on relatively few occasions over the 25 years of their existence testifies in part to the relatively rare calls which have been made upon them, but also reflects the difficulty in deciding when and how to utilise emergency vaccination. Nevertheless, in an era of increasing global risks of the spread of foot and mouth disease, banks will most certainly continue to have strategic and tactical importance in the control of this most readily communicable of animal diseases.

Animals↗
PubMed2000

Carriers of foot-and-mouth disease virus: a review.

This review describes current knowledge about persistent foot-and-mouth disease virus (FMDV) infections, the available methods to detect carrier animals, the properties of persisting virus, the immunological mechanisms, and the risk of transmission. In particular, knowledge about the carrier state, the period in which virus can be isolated from animals 28 days or longer post infection, is important, because the risk that animals may carry the virus will influence the diagnostic and preventive measures that need to be taken. Although many years of research have led to much knowledge about foot-and mouth disease and its causative agent, there are still numerous aspects of the virus and the disease that are not yet fully understood. Areas for further research on persistence of FMDV are discussed.

Animals↗
PubMed1990

Foot-and-mouth disease virus in the llama (Lama glama): diagnosis, transmission, and susceptibility.

Foot-and-mouth disease virus (FMDV) was shown to be transmitted from either cattle to llamas, llamas to swine (interspecies), or llamas to llamas (intraspecies). Response to FMDV varied greatly in the 6 llamas studied; 3 llamas developed generalized clinical disease with mild pyrexia, 2 after intradermolingual inoculation, and 1 after exposure to a calf infected with FMDV serotype A24. Another contact llama developed vesicular lesions on all 4 extremities but no oral lesions. Two contact llamas, in separate study groups, did not seroconvert or develop clinical signs of FMDV infection. All 4 llamas showing clinical disease developed virus-neutralizing antibodies against FMDV A24 and antibodies against the virus-infection-associated antigen. Virus-neutralizing antibody titers remained elevated for over 200 days postinoculation or exposure. Antibodies to virus-infection-associated antigen were detected several days after virus-neutralizing antibody appeared and became weaker 100-125 days post-FMDV exposure in 3 of the 4 clinically affected llamas. One inoculated llama was still positive for virus-infection-associated antigen at 360 days after inoculation. Foot-and-mouth disease virus A24 was not detected from esophageal-pharyngeal fluid specimens beyond 8 days postexposure using in vitro techniques.

Animals↗
PubMed1976

[Attempts to adapt BNK cells to cultivation in suspension and study of the antigenic properties of foot-and-mouth diseases viruses obtained from them].

Experiments were carried out to cultivate the foot-and-mouth disease virus under laboratory conditions in a suspension of the BHK-21 cell line. Results showed that the number of cells cultivated in a susfor 48 to 72 hours of incubation reaches up to 2.2 X 10(6). It was also found that certain conditions should be observed for the successful cultivation of the cells in suspension, such as aeration, pH, and respective temperature. It was demonstrated that foot-and-mouth diseases viruses obtained from BHK cells propagating in suspension possess good antigenic and immunogenic properties.

Animals↗
PubMed1999

Improvement of the immune response to foot and mouth disease virus vaccine in calves by using Avridine as adjuvant.

The epidemiological analysis of the cattle population during the eradication plan of foot and mouth disease (FMD) in Argentina clearly indicated a higher incidence of the disease in animals within their first year of age. It is important to improve the efficacy of the vaccination in those animals. In a previous report, we have shown the effect of an immunomodulator, Avridine (Avr), in the enhancement of the immune response elicited by FMD virus (FMDV) vaccines in experimental hosts [Berinstein, A., Pérez Filgueira, M., Schudel, A., Zamorano, P., Borca, M., Sadir, A.M., 1993. Avridine and LPS from Brucella ovis: effect on the memory induced by foot-and-mouth disease virus vaccination in mice. Vaccine 11, 1295-1301]. In this report, we analyze the effect of Avr in the improvement of the anti-FMDV immune response elicited in young animals immunized with a tetravalent vaccine. The anti-FMDV antibody response was evaluated using a liquid-phase blocking sandwich ELISA (LPBE) [Smitsaart, E.N., Zanelli, M., Rivera, I., Fondevila, N., Compaired, D., Maradei, E., Bianchi, T., O'Donnell, V., Schudel, A.A., 1998. Assessment using ELISA of the herd immunity levels induced in cattle by foot and mouth disease oil vaccines. Prev. Vet. Med 33, 283-296] while the cellular response was detected using an antigen specific lymphoproliferative test [Zamorano, P., Wigdorovitz, A., Chaher, M., Fernández, F., Sadir, A., Borca, M., 1994. Localization of B and T cell epitopes on a synthetic peptide containing the major immunogenic site of FMDV O1 Campos. Virology 201, 383-387]. The results show that, while no differences were detected in the cellular response, the anti-FMDV antibody reaction was significantly (<0.05) higher in animals immunized with the immunogen containing Avr. At 90 days post vaccination, 89-100% of the animals immunized with Avr presented predicted protection (PP) higher than 82% while just 50-61% of the animals immunized with vaccine without immunomodulator presented that characteristic. Also, it is shown that the increase in the anti-FMDV antibody titre in animals immunized with the vaccine containing Avr was mediated by an increase in the levels of both IgG1 and IgG2 which presented a significative correlation with LPELISA antibodies titres. It is concluded that the addition of Avr in the FMDV vaccines improve the immune status of the calves, the cattle population that suffers the highest epidemiological risk.

Adjuvants, Immunologic↗
PubMed1986

Characterization of foot-and-mouth disease virus gene products with antisera against bacterially synthesized fusion proteins.

Defined segments of the cloned foot-and-mouth disease virus genome corresponding to all parts of the coding region were expressed in Escherichia coli as fusions to the N-terminal part of the MS2-polymerase gene under the control of the inducible lambda PL promoter. All constructs yielded large amounts of proteins, which were purified and used to raise sequence-specific antisera in rabbits. These antisera were used to identify the corresponding viral gene products in 35S-labeled extracts from foot-and-mouth disease virus gene products in the nucleotide sequence, to identify precursor-product relationships, and to detect several foot-and-mouth disease virus gene products not previously identified in vivo or in vitro.

Animals↗
PubMedDate not supplied

Chemical basis of antigenic variation in foot-and-mouth disease virus.

One of the difficulties in controlling foot and mouth disease by vaccination is the occurrence of the virus as seven distinct serotypes because immunity conferred by vaccination against one serotype leaves the animals susceptible to infection by the other six. Moreover, the antigenic variation, even within a serotype, can be so great that immunity against the homologous strain of virus need not necessarily ensure protection against infection by other viruses within that serotype. Here we report the separation of three natural antigenic variants, distinguishable in cross-neutralization tests from an isolate of foot-and-mouth disease virus (FMDV). The serological differences could also be demonstrated by antisera elicited by synthetic peptides corresponding to residues 141-160 of the capsid polypeptide VP1, showing that this region contains a major immunogenic site of the virus. The results have practical implications for the choice of viruses for vaccine production.

Amino Acid Sequence↗
PubMed1981

Serological differentiation of foot-and-mouth disease virus on electron microscope grids coated with protein A and antibody.

A serological technique using electron microscope grids coated with protein A and antiserum was able to detect foot-and- mouth disease virus particles in oesophageal-pharyngeal fluids from infected cattle without the need for prior concentration of the sample. The technique was adapted to differentiate serologically among foot-and-mouth disease virus types A, O and C with antigen-adsorbed sera. When grids were coated with heterotypic antigenadsorbed antisera, the homotypic antigen could be observed in viral specimens containing 10(5) PFU/mL, but the heterotypic antigen was not visualized until its concentration was about tenfold higher. Grids coated with the appropriate antigen-adsorbed antiserum can thus be used to indicate foot-and-mouth disease viral serotypes in specimens containing less than 10(6) PFU/mL.

Animals↗
PubMed2005

Retrospective genetic analysis of SAT-1 type foot-and-mouth disease outbreaks in southern Africa.

In areas where foot-and-mouth disease (FMD) is endemic in wildlife hosts, such as the Kruger National Park (KNP) in South Africa, control measures are in place that ensure that potentially infected antelope and buffalo do not come into close contact with domestic animals. In South Africa several SAT-1 outbreaks occurred nearly simultaneously in cattle and impala between 1971-1981. Phylogenetic analysis based on partial 1D gene nucleotide sequencing indicated that several of these outbreaks were linked and it is probable that disease spread from the intermediary impala antelope host to cattle in close proximity. Evidence was found for the involvement of viruses from a single KNP genotype in precipitating outbreaks in impala over a 10-year period. In addition, several unrelated outbreaks affecting cattle and impala occurred within a single year. Characterisation of outbreak strains from Botswana similarly revealed that a single genotype affected different species over a 10-year period and that transboundary spread of SAT-1 virus occurred on at least one occasion. This retrospective analysis of outbreak strains has clearly demonstrated that FMD control policies that address the role of antelope as intermediaries in disease transmission are crucial as these wildlife species play an important role in disease dissemination.

Africa, Southern↗
PubMed2004

Re-emergence of foot-and-mouth disease in Botswana.

The re-emergence of foot-and-mouth disease (FMD) in Botswana is reported. The disease outbreak occurred in the Matsiloje Extension Area of Francistown veterinary district situated in the northeastern part of the country in an Office International des épízooties (OIE) recognized FMD free zone without vaccination. The disease affected cattle only and did not spillover into sheep and goats resident in the same extension area, as demonstrated by lack of seroconversion to FMD when tested. The virus isolate associated with the outbreak was identified as FMD virus; Southern African Territories (SAT) type SAT-2. The disease outbreak is discussed in relation to FMD outbreaks that have occurred previously within and outside Botswana.

Animals↗
PubMed2005

Studies of the outbreaks of foot and mouth disease in West Bengal, India, between 1985 and 2002.

Foot and mouth disease (FMD) is the major disease constraint on international trade in livestock and their products. In the state of West Bengal, India, 1,082 FMD outbreaks were reported in the 18 years from 1985 to 2002. Of the prevalent four serotypes, O type FMD virus accounted for the most outbreaks (67%), followed by Asia-1 virus type (15%) and A virus type (14%). Outbreaks of the type C FMD virus were least prevalent (4%), and no cases have been recorded since 1996. The study shows clearly that incidences were highest during the winter months and in the alluvial agro-climatic zones. The distribution and density of the FMD-susceptible population in different districts of the state also played major role in disease incidences. Due to the unrestricted movements of animals among different cattle markets, the disease was transmitted either by direct contact or by aerosols from infected to healthy animals. Cattle suffered most from the disease, accounting for about 95% of the cases. The monitoring of the disease documented in this study provides information about the endemicity of the disease that can help to formulate an effective strategy for an FMD control programme.

Animals↗