Foot-and-mouth disease virus lacking the VP1 G-H loop: the mutant spectrum uncovers interactions among antigenic sites for fitness gain.
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The Arg-Gly-Asp (RGD) triplet found in the G-H loop of capsid protein VP1 of foot-and-mouth disease virus (FMDV) is critically involved in the interaction of FMDV with integrin receptors and with neutralizing antibodies. Multiplication of FMDV C-S8c1 in baby hamster kidney 21 (BHK-21) cells selected variant viruses exploiting alternative mechanisms of cell recognition that rendered the RGD integrin-binding triplet dispensable for infectivity. By constructing chimeric viruses, we show that dispensability of the RGD in these variant FMDVs can be extended to surrounding amino acid residues. Replacement of eight amino acid residues within the G-H loop of VP1 by an unrelated FLAG marker yielded infectious virus. Evolution of FLAG-containing viruses in BHK-21 cells generated complex quasispecies in which individual mutants included amino acid replacements at other antigenic sites of FMDV. Inclusion of such replacements in the parental FLAG clone resulted in an increase of relative fitness of the viruses. These results suggest structural or functional connections between antigenic sites of FMDV and underscore the value of mutant spectrum analysis for the identification of fitness-promoting genetic modifications in viral populations. The possibility of producing viable viruses lacking antigenic site A may find application in the design of new anti-FMD vaccines. (+info)
Dynamics of the 2001 UK foot and mouth epidemic: stochastic dispersal in a heterogeneous landscape.
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Foot-and-mouth is one of the world's most economically important livestock diseases. We developed an individual farm-based stochastic model of the current UK epidemic. The fine grain of the epidemiological data reveals the infection dynamics at an unusually high spatiotemporal resolution. We show that the spatial distribution, size, and species composition of farms all influence the observed pattern and regional variability of outbreaks. The other key dynamical component is long-tailed stochastic dispersal of infection, combining frequent local movements with occasional long jumps. We assess the history and possible duration of the epidemic, the performance of control strategies, and general implications for disease dynamics in space and time. (+info)
Cleavage of translation initiation factor 4AI (eIF4AI) but not eIF4AII by foot-and-mouth disease virus 3C protease: identification of the eIF4AI cleavage site.
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The translation initiation factor eIF4A is cleaved within mammalian cells infected by foot-and-mouth disease virus (FMDV). The FMDV 3C protease cleaves eIF4AI (between residues E143 and V144), but not the closely related eIF4AII. Modification of eIF4AI, to produce a sequence identical to eIF4AII around the cleavage site, blocked proteolysis. Alignment of mammalian eIF4AI onto the three-dimensional structure of yeast eIF4A located the scissile bond within an exposed, flexible portion of the molecule. The N- and C-terminal cleavage products of eIF4AI generated by FMDV 3C dissociate. Cleavage of eIF4AI by FMDV 3C is thus expected to inactivate it. (+info)
How RNA viruses exchange their genetic material.
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One of the most unusual features of RNA viruses is their enormous genetic variability. Among the different processes contributing to the continuous generation of new viral variants RNA recombination is of special importance. This process has been observed for human, animal, plant and bacterial viruses. The collected data reveal a great susceptibility of RNA viruses to recombination. They also indicate that genetic RNA recombination (especially the nonhomologous one) is a major factor responsible for the emergence of new viral strains or species. Although the formation and accumulation of viral recombinants was observed in numerous RNA viruses, the molecular basis of this phenomenon was studied in only a few viral species. Among them, brome mosaic virus (BMV), a model (+)RNA virus offers the best opportunities to investigate various aspects of genetic RNA recombination in vivo. Unlike any other, the BMV-based system enables homologous and nonhomologous recombination studies at both the protein and RNA levels. As a consequence, BMV is the virus for which the structural requirements for genetic RNA recombination have been most precisely established. Nevertheless, the previously proposed model of genetic recombination in BMV still had one weakness: it could not really explain the role of RNA structure in nonhomologous recombination. Recent discoveries concerning the latter problem give us a chance to fill this gap. That is why in this review we present and thoroughly discuss all results concerning nonhomologous recombination in BMV that have been obtained until now. (+info)
Integrin alphavbeta1 is a receptor for foot-and-mouth disease virus.
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Infection by field strains of Foot-and-mouth disease virus (FMDV) is initiated by binding to certain species of arginine-glycine-aspartic acid (RGD)-dependent integrin including alphavbeta3 and the epithelial integrin alphavbeta6. In this report we show that the integrin alphavbeta1, when expressed as a human/hamster heterodimer on transfected CHOB2 cells, is a receptor for FMDV. Virus binding and infection mediated by alphavbeta1 was inefficient in the presence of physiological concentrations of calcium and magnesium but were significantly enhanced by reagents that activate the integrin and promote ligand binding. The ability of chimeric alpha5/alphav integrin subunits, in association with the beta1 chain, to bind FMDV and mediate infection matched the ligand binding specificity of alphavbeta1, not alpha5beta1, thus providing further evidence for the receptor role of alphavbeta1. In addition, data are presented suggesting that amino acid residues near the RGD motif may be important for differentiating between the binding specificities of alphavbeta1 and alphavbeta6. (+info)
Isolation of foot-and-mouth disease virus from Japanese black cattle in Miyazaki Prefecture, Japan, 2000.
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Four outbreaks of foot-and-mouth disease (FMD) occurred from March to May 2000 in Miyazaki and Hokkaido Prefectures, Japan. FMD virus isolation was achieved by sampling probang materials from Japanese Black cattle in the third case found in Miyazaki Prefecture. The probang materials were inoculated to bovine kidney (BK) and bovine thyroid cell cultures. CPE was observed in the BK at two days post-inoculation. Specific amplified DNA segments for FMD virus (FMDV) were detected by reverse transcriptase polymerase chain reaction in the culture fluid. The FMDV was identified as type O by enzyme-linked immunosorbent assay (ELISA) for antigen detection and the nucleotide sequence encoding the VPI was determined. This FMDV is a strain that is widespread in Pan-Asia and was designated as O/JPN/2000 by the World Reference Laboratory of the Pirbright Institute, England. This report marks the first isolation of FMDV in Japan. (+info)
A replication-competent chimera of plant and animal viruses.
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Human, animal, fungal, and plant viruses encode papain-like proteinases that function in polyprotein processing, RNA synthesis, and virus-host interactions. To compare the functional profiles of diverse papain-like proteinases, we replaced a proteinase gene of the beet yellows virus (BYV) with those derived from equine arteritis virus (EAV), foot-and-mouth disease virus (FMDV), and the fungal virus CHV1. We found that, although each of the foreign proteinases efficiently processed the viral polyprotein, only the EAV proteinase supported vigorous replication of the chimeric BYV in plant protoplasts. This result demonstrated that the proteinases of BYV and EAV, but not FMDV or CHV1, provide a function that is critical for genome replication and that is separable from polyprotein processing. Further characterization of the BYV-EAV chimera revealed that BYV proteinase is also required for virus invasion and cell-to-cell movement. Thus, the same viral protein can combine both replication-related functions shared by plant and animal viruses and specialized functions in virus-host interactions. (+info)
Antigenic sites of foot-and-mouth disease virus (FMDV): an analysis of the specificities of anti-FMDV antibodies after vaccination of naturally susceptible host species.
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Of the known neutralizing antigenic sites of foot-and-mouth disease virus (FMDV), site 1 or A, formed in part by the G-H loop of VP1, has historically been considered immunodominant because of evidence implicating its importance in the induction of a protective immune response. However, no systematic study has been done to determine the relative importance of the various specificities of antibodies against the known neutralizing antigenic sites of FMDV in the polyclonal immune response of a natural host after vaccination. In this report, we have adopted a monoclonal antibody-based competition ELISA and used antibodies specific to sites 1, 2 and 3 to provide some insight into this issue. Following vaccination of the three main target species, cattle, pigs and sheep, with an O1 serotype strain, results indicate that none of these three antigenic sites can be considered immunodominant in a polyclonal serum. Interestingly, pigs did not respond to epitopes on the carboxy terminus end of VP1 as efficiently as the ruminant species. In addition to the known sites, other as yet undefined sites might also be important in the induction of a protective immune response. Possible implications for the design of new vaccine strategies for foot-and-mouth disease are discussed. (+info)