Foot-and-mouth disease virus evolution: exploring pathways towards virus extinction

Area of Science:

• Virology
• Molecular Biology
• Genetics

Background:

• Foot-and-mouth disease virus (FMDV) is a highly variable RNA virus.
• FMDV exhibits quasispecies dynamics, where diverse mutant spectra are generated.
• Minority viral subpopulations can become dominant due to environmental changes or population fluctuations.

Purpose of the Study:

• To investigate the mechanisms of FMDV genetic variation and survival under different conditions.
• To compare FMDV resistance to extinction during bottleneck passage versus mutagenesis.
• To gain insights into viral quasispecies dynamics for developing novel antiviral strategies.

Main Methods:

• Serial bottleneck passages of FMDV populations.
• Viral replication in the presence of mutagenic base or nucleoside analogs.
• Analysis of mutation accumulation and relative fitness in FMDV genomes.

Main Results:

• FMDV survives serial bottleneck passages with linear mutation accumulation and compensatory mutations.
• Replication with mutagens increases mutant spectra complexity and can lead to extinction via error catastrophe.
• Low relative fitness and viral load promote FMDV extinction in cell culture.

Conclusions:

• Compensatory mutations are critical for FMDV survival during bottleneck passages.
• Enhanced mutagenesis can drive FMDV towards extinction by exceeding an error threshold.
• Comparing these extinction routes offers insights into quasispecies dynamics and potential antiviral therapies targeting error catastrophe.