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[Several criteria of evaluation of foot-and-mouth disease virus reproduced in cell cultures in suspension].

The study of the plaques produced by viruses Asia and O1 reveals different properties which may depend on the virus or on the cell or its method of culture. Antigenic differences and subsequent immunological differences correspond to differences in plaques. On the other hand, the cell line in suspension evolves both in its morphology and its receptivity during the passages. All these variations imply the observations of quantitative and qualitative criteria of evaluation in order to prepare vaccines from viruses similar to viruses specific to a given epizooty.

Animals↗

[Production of purified foot-and-mouth disease virus antigens and the specific sera against them].

It was demonstrated that the use of laboratory techniques could be contributive to the production of purified antigens of the F.M.D. virus, such a-140 S, 12 S, and VIA. The isolated purified antigens were used to immunize guinea pigs, obtaining specific antisera against them. It was found that the latter contained specific complement-fixing and precipitating antibodies, while the 140 S serum also had neutralizing antibodies. The produced 140 S serum contained certain amounts of 12 S antibodies, which was considered to be the result of a spontaneous degradation of the 140 S antigen.

Animals↗

Opportunities for machine learning to predict cross-neutralization in FMDV serotype O.

Accurately estimating cross-neutralization between serotype O foot-and-mouth disease viruses (FMDVs) is critical for guiding vaccine selection and disease management. In this study, we developed a machine learning approach to estimate r1 values-an established measure of antigenic similarity-using VP1 sequence data and published virus neutralization titer (VNT) results. Our dataset comprised 108 serum-virus pairs representing 73 distinct FMDV strains. We applied Boruta feature selection and random forest classifiers, optimizing model performance through tenfold cross-validation and sub-sampling to address class imbalance. Predictors included pairwise amino acid distances, site-specific polymorphisms, and differences in potential N-glycosylation sites. Using a 0.3 r1 threshold to define cross-neutralization, the final model achieved high accuracy (0.96), sensitivity (0.93), and specificity (0.96) in training, and performed robustly on independent test sets - accuracy was 0.75 (95% CI 0.60 and 0.90), F1 score 0.86% and PPV 0.77. Importantly, key VP1 residues-positions 48, 100, 135, 150, and 151-emerged as strong predictors of antigenic relationships. Our results demonstrate the utility of integrating routinely generated genomic data with machine learning to inform vaccine candidate selection and anticipate immune interactions among circulating FMDV strains. This approach offers a practical tool for accelerating vaccine decision-making and can be adapted to other FMDV serotypes. The latest version of the r1 predictive model is available for access via a Shiny dashboard (https://dmakau.shinyapps.io/PredImmune-FMD/).

Foot-and-Mouth Disease Virus↗

Comparison of the antibodies elicited by the individual structural polypeptides of foot-and mouth disease and polio viruses.

Antibody produced against preparations of VP1, one of the four structural polypeptides of foot-and-mouth disease virus, neutralized the virus and reacted with both full and empty particles in radioimmunoassays (RIA). Antiserum against VP2 reacted with artificial empty particles of the virus but not with full particles. In contrast, none of the individual polypeptides of poliovirus produced antisera which neutralized the virus nor reacted with it in RIA. However, antisera produced with VP1 and VP2 reacted with artificial empty particles in RIA.

Animals↗

Clonality and intracellular polyploidy in virus evolution and pathogenesis.

In the present article we examine clonality in virus evolution. Most viruses retain an active recombination machinery as a potential means to initiate new levels of genetic exploration that go beyond those attainable solely by point mutations. However, despite abundant recombination that may be linked to molecular events essential for genome replication, herein we provide evidence that generation of recombinants with altered biological properties is not essential for the completion of the replication cycles of viruses, and that viral lineages (near-clades) can be defined. We distinguish mechanistically active but inconsequential recombination from evolutionarily relevant recombination, illustrated by episodes in the field and during experimental evolution. In the field, recombination has been at the origin of new viral pathogens, and has conferred fitness advantages to some viruses once the parental viruses have attained a sufficient degree of diversification by point mutations. In the laboratory, recombination mediated a salient genome segmentation of foot-and-mouth disease virus, an important animal pathogen whose genome in nature has always been characterized as unsegmented. We propose a model of continuous mutation and recombination, with punctuated, biologically relevant recombination events for the survival of viruses, both as disease agents and as promoters of cellular evolution. Thus, clonality is the standard evolutionary mode for viruses because recombination is largely inconsequential, since the decisive events for virus replication and survival are not dependent on the exchange of genetic material and formation of recombinant (mosaic) genomes.

Animals↗

[Physico-chemical properties of swine vesicular disease virus].

Titration of SVDV on primary pig kidney cell cultures revealed a plating efficiency of less than or equal to 0,9 X 10(-3). Concentration and purification of the SVD-Virus propagated on pig kidney cell cultures were done by chloroform treatment, adsorption, differential- and density gradient centrifugation. The following physical parameters were found: SVDV is an isometrical RNA-virus having a diameter of 25,1 +/- 1,0 nm. It is resistent to the action of chloroform, ether and pH. The virus has a sedimentation coefficient of 156 +/- 3S and a bouyant density in CsCl of 1,33 +/- 0,01 g/ml. Within the family of picornaviruses the SVDV belongs to the subgroup of enteroviruses and can be distinguished from the foot-and-mouth disease virus by the difference in pH-sensitivity and bouyant density in CsCl.

Animals↗

Redox cycling of viral RNA polymerase controls picornavirus replication.

Picornaviruses, including foot-and-mouth disease virus (FMDV), enterovirus 71 (EV71) and encephalomyocarditis virus (EMCV), are important pathogens that cause fever, herpes, and myocarditis in humans and animals. The interplay between picornaviruses and their hosts remains enigmatic. Here we perform porcine genome-wide CRISPR/Cas9 screens and identify methionine sulfoxide reductase B3 (MSRB3) as an essential factor for FMDV. MSRB3 deficiency inhibits FMDV replication. Mechanistically, MSRB3 eliminates methionine oxidation of FMDV 3D polymerase and stabilizes its expression. Further studies show that radical SAM domain-containing protein 1 (RSAD1) catalyzes methionine oxidation of FMDV 3D polymerase and promotes its aggregation and subsequent degradation through the autophagy-lysosome pathway. Importantly, RSAD1-MSRB3-mediated redox modification also affects the stability of 3D polymerases of EV71 and EMCV, and regulates their infectivity and pathogenesis both in vitro and in vivo. Collectively, this study corroborates that RSAD1-MSRB3-mediated redox cycling of 3D polymerase plays a conserved function in modulating picornavirus infection, providing insights into viral pathogenesis and broad-spectrum antiviral development.

Animals↗

4D-DIA proteomics reveals distinct proteolytic landscapes induced by mechanical stress, Agrobacterium, and a viral capsid precursor.

Nicotiana benthamiana is a widely used platform for plant molecular farming, yet recombinant protein yields are frequently compromised by the host's innate defense mechanisms, particularly proteolytic degradation. While the general effects of Agroinfiltration are known, the distinct contributions of mechanical injury, bacterial perception, and product-specific stress remain poorly resolved. Here we utilized high-depth 4D-DIA proteomics to dissect the host response across three dimensions: physical stress (buffer infiltration), pathogen-associated stress (Agrobacterium), and product-associated stress (GFP vs. the FMDV capsid precursor P1_2A). We demonstrate that buffer infiltration is not a neutral event but an independent inducer of cell wall remodeling and oxidative stress. By filtering out these background effects, we defined a core Agrobacterium-responsive proteome characterized by a growth-defense trade-off. We also expanded the known protease repertoire of N. benthamiana to 1,505 enzymes through improved genomic annotation. We found that the expression of the FMDV capsid precursor P1_2A was associated with a distinct and more pronounced protease profile compared to soluble GFP, characterized by the upregulation of subtilases and cysteine proteases. These findings suggest that host proteolytic responses vary with the recombinant cargo, a factor worth considering when designing engineering strategies for the production of complex biopharmaceuticals in plants.

Proteomics↗