Nucleic Acid Polymerase Fidelity and Viral Population Fitness

Viral polymerases are essential for the maintenance and expression of the genomes of all viruses. The fidelity of polymerase-catalyzed nucleotide addition varies between classes of nucleic acid polymerases. Here we present a kinetic, thermodynamic, and structural description of the process employed by polymerases to modulate the accuracy of nucleotide addition. Direct connections between polymerase fidelity and virus biology are discussed that lead to the general conclusion that polymerase fidelity is tuned by natural selection to optimize viral population genotypic diversity and, consequently, viral competitiveness in the dynamic and hostile environment of the cell. Finally, we discuss the potential of exploiting the optimized nature of viral polymerase fidelity for development of strategies to treat and prevent viral infections.