Genetic Instability of RNA Viruses

Barr, J.N.; Fearns, R.

Despite having very limited coding capacity, RNA viruses are able to withstand challenge of antiviral drugs, cause epidemics in previously exposed human populations, and, in some cases, infect multiple host species. They are able to achieve this by virtue of their ability to multiply very rapidly, coupled with their extraordinary degree of genetic heterogeneity. RNA viruses exist not as single genotypes, but as a swarm of related variants, and this genomic diversity is an essential feature of their biology. RNA viruses have a variety of mechanisms that act in combination to determine their genetic heterogeneity. These include polymerase fidelity, error-mitigation mechanisms, genomic recombination, and different modes of genome replication. RNA viruses can vary in their ability to tolerate mutations, or “genetic robustness,” and several factors contribute to this. Finally, there is evidence that some RNA viruses exist close to a threshold where polymerase error rate has evolved to maximize the possible sequence space available, while avoiding the accumulation of a lethal load of deleterious mutations. We speculate that different viruses have evolved different error rates to complement the different “life-styles” they possess.