Foot-and-mouth disease virus: biology and prospects for disease control

Foot-and-mouth disease virus (FMDV) is the causative agent of a disease that constitutes one of the main animal health concerns, as evidenced by the devastating outbreaks that occurred in different areas of the world over the last few years. In this review, we summarise important features of FMDV, aspects of its interactions with cells and hosts as well as current and new strategies for FMD control by vaccination.     

口蹄疫病毒感染BHK—21细胞的代谢热谱研究

本文应用高灵敏度的LKB2277生物活性检测仪测定FMDV感染BHK-21细胞的代谢热谱,并与传统方法测定的一步生长曲线进行比较,二者具有显著的相似性。结果表明,微量热法通过对细胞及其受病毒感染的细胞体系代谢热的测定,能有效地监测病毒在宿主细胞内增殖的过程。该方法还提供了一种动态连续分析病毒感染增殖的新手段。     

口蹄疫病毒感染BHK-21细胞的代谢热谱研究

本文应用高灵敏度的LKB2277生物活性检测仪测定FMDV感染BHK-21细胞的代谢热谱,并与传统方法测定的一步生长曲线进行比较,二者具有显著的相似性.结果表明,微量热法通过对细胞及其受病毒感染的细胞体系代谢热的测定,能有效地监测病毒在宿主细胞内增殖的过程.该方法还提供了一种动态连续分析病毒感染增殖的新手段.     

Foot-and-mouth disease virus-induced RNA polymerase is associated with Golgi apparatus.

Electrophoretic analysis of the Golgi apparatus isolated by differential centrifugation from radiolabeled cells infected with foot-and-mouth disease virus showed about 10 protein bands. The virus-induced RNA polymerase was identified by immunoprecipitation and electron microscope staining procedures. Pulse-chase experiments indicated that the polymerase passed through the Golgi apparatus in less than 1 h.     

Free radicals and disease in man

Free radicals and related activated electronic species are produced in biological systems in antimicrobial defense, through the action of the mixed function monooxygenases, by various oxidative enzymes such as xanthine oxidase, and by autooxidations mediated by such agents as heavy metals or quinones. While the evidence is circumstantial, excessive unconfined or inappropriate production of radical species in inflammation, the metabolism of exogenous chemicals, or through autooxidation probably plays a significant role in human disease.     

Foot-and-mouth disease virus 2A oligopeptide mediated cleavage of an artificial polyprotein.

We describe the construction of a plasmid (pCAT2AGUS) encoding a polyprotein in which a 19 amino acid sequence spanning the 2A region of the foot-and-mouth disease virus (FMDV) polyprotein was inserted between the reporter genes chloramphenicol acetyl transferase (CAT) and beta-glucuronidase (GUS) maintaining a single, long open reading frame. Analysis of translation reactions programmed by this construct showed that the inserted FMDV sequence functioned in a manner similar to that observed in FMDV polyprotein processing: the CAT2AGUS polyprotein underwent a cotranslational, apparently autoproteolytic, cleavage yielding CAT-2A and GUS. Analysis of translation products derived from a series of constructs in which sequences were progressively deleted from the N-terminal region of the FMDV 2A insertion showed that cleavage required a minimum of 13 residues. The FMDV 2A sequence therefore provides the opportunity to engineer either whole proteins or domains such that they are cleaved apart cotranslationally with high efficiency.     

Foot-and-mouth disease virus and poliovirus particles contain proteins of the replication complex.

Nonstructural proteins 2C, 3CD, 3C, and 3D, and the cellular protein actin, are present in highly purified preparations of foot-and-mouth disease virus (FMDV) and poliovirus. They remain bound in variable amounts to the RNAs when the RNAs are extracted from the viruses with phenol or phenol-sodium dodecyl sulfate (SDS) and, for FMDV, when the RNA is released from the particles by a lowering of the pH below 7. RNA prepared by these methods is rapidly degraded at 37 degrees C, particularly in the presence of NH4+ ions, but hydrolysis can be prevented by antibody against Escherichia coli-expressed 3D, indicating that it is the RNA polymerase that has nuclease activity. In contrast, virion RNA from which the nonstructural proteins and actin have been removed by extraction with guanidine thiocyanate-phenol-chloroform or proteinase K-phenol is stable at 37 degrees C, although its specific infectivity is lower than that of the RNA extracted with phenol or phenol-SDS. The possible implications of the close association of replication complex proteins with the RNA in virus particles are discussed.     

Foot-and-mouth disease virus: cause of the recent crisis for the UK livestock industry

The recent outbreak of foot-and-mouth disease (FMD) in the United Kingdom is a stark reminder of the economic devastation that this disease can wreak. Tracing the origin of such an outbreak is an essential part of disease control. Modern molecular methods have been in place for a number of years to enable scientists to identify unambiguously the strain of virus responsible. However, tracing the precise origin of such a strain is not so straightforward because the virus can move rapidly around the world with legal and illegal trade in animals and animal products. This short review describes the virus, its control and epidemiology.     

Foot-and-mouth disease virus mutant with decreased sensitivity to ribavirin: implications for error catastrophe

The nucleoside analogue ribavirin (R) is mutagenic for foot-and-mouth disease virus (FMDV). Passage of FMDV in the presence of increasing concentrations of R resulted in the selection of FMDV with the amino acid substitution M296I in the viral polymerase (3D). Measurements of progeny production and viral fitness with chimeric viruses in the presence and absence of R documented that the 3D substitution M296I conferred on FMDV a selective replicative advantage in the presence of R but not in the absence of R. In polymerization assays, a purified mutant polymerase with I296 showed a decreased capacity to use ribavirin triphosphate as a substrate in the place of GTP and ATP, compared with the wild-type enzyme. The results suggest that M296I has been selected because it attenuates the mutagenic activity of R with FMDV. Replacement M296I is located within a highly conserved stretch in picornaviral polymerases which includes residues that interact with the template-primer complex and probably also with the incoming nucleotide, according to the three-dimensional structure of FMDV 3D. Given that a 3D substitution, distant from M296I, was associated with resistance to R in poliovirus, the results indicate that picornaviral polymerases include different domains that can alter the interaction of the enzyme with mutagenic nucleoside analogues. Implications for lethal mutagenesis are discussed.