Picornavirus RNA Recombination Counteracts Error Catastrophe

Area of Science:

• Virology
• Molecular Biology
• Genetics

Background:

• Picornaviruses replicate RNA rapidly but are prone to mutations, leading to error catastrophe.
• Viral RNA recombination is theorized to counteract this mutational burden.

Purpose of the Study:

• To investigate the roles of poliovirus RNA-dependent RNA polymerase (RDRP) fidelity and recombination in preventing error catastrophe.
• To determine if RNA recombination is essential for picornaviruses to evade ribavirin-induced error catastrophe.

Main Methods:

• Utilized specific mutations (G64S and L420A) in the poliovirus RDRP to alter polymerase fidelity and recombination rates.
• Assessed the impact of these mutations on ribavirin-induced error catastrophe.

Main Results:

• The G64S mutation increased RDRP fidelity and conferred resistance to ribavirin-induced error catastrophe, but only when RNA recombination was at wild-type levels.
• The L420A mutation inhibited RNA recombination, exacerbated ribavirin-induced error catastrophe, and abolished the protective effect of the high-fidelity G64S polymerase.
• These findings demonstrate that viral RNA recombination is required for poliovirus to overcome ribavirin-induced error catastrophe.

Conclusions:

• Picornavirus RDRPs influence error catastrophe through both RNA synthesis fidelity and recombination.
• Viral RNA recombination is a critical mechanism for picornaviruses, like poliovirus, to counteract and avoid error catastrophe, particularly under mutagenic stress.
• The conserved L420 residue suggests RNA recombination is a common strategy for picornaviruses to maintain genome integrity and viability.