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Homologous interference by a foot-and-mouth disease virus strain attenuated for cattle
Abstract:
An attenuated strain of foot-and-mouth disease virus (FMDV) of the A24 Cruzeiro subtype grew less well than wild-type virus in primary bovine fetal kidney (PBK) cells resulting in a 4-log lowered efficiency of plaque formation. Both wild-type and attenuated virus grew equally well in baby hamster kidney (BHK) cells and in suckling mice. Using PBK cells, virus-specific RNA of the wild-type accumulated up to 6 hours after infection. In contrast, PBK cells infected with the attenuated strain made less than 20 per cent of the RNA synthesized by wild-type virus. Infection of the cell with wild-type virus followed by superinfection with attenuated virus led to almost complete inhibition of viral RNA synthesis, an effect which is dependent on the concentration of input attenuated virus. Three subsequent undiluted successive passages of the attenuated virus resulted in a preparation which no longer interfered with wild-type RNA synthesis and which induced more of its own viral RNA synthesis in PBK cells. The basis of this interference was considered. Interference occurred intracellularly and was directed only against viruses within the genus FMDV. A role for interferon was ruled out. Attempts to demonstrate the physical presence of defective interfering (DI) particles of FMDV in the attenuated strain failed; but, cyclic patterns of infectivity were produced during successive undiluted passages.
Insights
An attenuated foot-and-mouth disease virus (FMDV) strain showed reduced RNA synthesis in bovine cells, causing interference. This interference was lost after serial passages, suggesting a loss of defective interfering properties.
Area of Science:
- Virology
- Molecular Biology
- Immunology
Background:
- Foot-and-mouth disease virus (FMDV) is a significant pathogen in livestock.
- Attenuated viral strains are crucial for vaccine development.
- Understanding viral interference mechanisms is key to controlling FMDV spread.
Purpose of the Study:
- To investigate the reduced growth and RNA synthesis of an attenuated FMDV strain in primary bovine fetal kidney (PBK) cells.
- To characterize the interference phenomenon observed with the attenuated FMDV strain.
- To explore the potential role of defective interfering (DI) particles in the observed interference.
Main Methods:
- Comparative growth studies of wild-type and attenuated FMDV in PBK, baby hamster kidney (BHK) cells, and suckling mice.
- Quantification of viral RNA synthesis in infected cells.
- Superinfection experiments to assess viral interference.
- Serial undiluted passages of the attenuated virus to study changes in interference properties.
Main Results:
- The attenuated FMDV strain exhibited significantly lower plaque formation and viral RNA synthesis in PBK cells compared to wild-type.
- Attenuated FMDV showed reduced RNA synthesis (<20%) in PBK cells.
- Superinfection with attenuated FMDV inhibited wild-type FMDV RNA synthesis in a dose-dependent manner.
- Serial passages of the attenuated virus led to the loss of interference activity and restoration of its own RNA synthesis.
- Interference was intracellular, specific to FMDV, and not mediated by interferon.
- Attempts to detect physical DI particles failed, but cyclic infectivity patterns emerged during passages.
Conclusions:
- The attenuated FMDV strain possesses properties that interfere with wild-type FMDV replication in bovine cells.
- This interference is likely mediated by factors other than interferon, possibly related to defective interfering particles, although their physical presence was not confirmed.
- The loss of interference after serial passages suggests a dynamic interaction between the attenuated virus and the host cell, potentially involving the generation and subsequent loss of defective genomes.