Lethal mutagenesis of an RNA plant virus via lethal defection

Area of Science:

• Virology
• Molecular Biology
• Plant Pathology

Background:

• Lethal mutagenesis is an antiviral strategy that increases viral mutation rates using mutagenic agents.
• The precise molecular mechanisms driving virus extinction via lethal mutagenesis remain incompletely understood.
• The lethal defection model proposes that replication-competent mutants drive virus populations toward extinction.

Purpose of the Study:

• To investigate the in vivo effects of lethal mutagenesis on tobacco mosaic virus (TMV) using 5-fluorouracil (5-FU).
• To elucidate the molecular mechanisms underlying 5-FU's antiviral activity against TMV in Nicotiana tabacum.

Main Methods:

• Systemic TMV infections were established in N. tabacum plants.
• Plants were treated with 5-FU, a mutagenic nucleobase analogue.
• Viral infectivity, viral load, and mutation profiles in specific genomic regions were analyzed.

Main Results:

• 5-FU treatment decreased TMV infectivity without altering viral load.
• Specific base transitions (A→G and U→C) were increased by 5-FU.
• While mutation frequency per molecule did not increase, the complexity and distribution of mutations were altered, particularly in the RNA-dependent RNA polymerase (RdRp) gene.

Conclusions:

• 5-FU exhibits an antiviral effect on TMV by disrupting the mutation-selection balance.
• These findings support the lethal defection model for lethal mutagenesis in plant RNA viruses.
• This study provides a foundation for exploring lethal mutagens in plant-virus systems.