Limiting viral diversity lowers virulence
RNA viruses are characterised by an extreme genetic diversity due to their high mutation rates. In practice, this means that RNA virus populations exist as a collection of genetically similar, yet diverse variants which behave like a single species. This phenomenon is described by the term quasispecies and functionally, it is believed to drive the high evolutionary rate of these viruses.The genetic heterogeneity of RNA viruses is attributed to the low fidelity nature of the viral RNA polymerases which lack the proof-reading capacity of DNA polymerases. However, other driving forces such as RNA stability, recombination, and selective pressure, seem to drive the emergence of new mutations. With this in mind, the EU-funded 'The role of genetic diversity of RNA viruses in virulence and pathogenesis' (RNAVIRUSDIVNPATHO) project aimed to connect the nature of the viral RNA polymerase with the observed high mutation frequencies of RNA viruses.Accumulating evidence indicates that modulating the fidelity of the RNA polymerase has the capacity to restrict the extent of genetic diversity present in a viral population. Researchers worked on poliovirus and Coxsackie virus to confirm this correlation and also showed that restricting population diversity reduces virulence. Another important finding entailed the cooperation between wild type and restricted virus species to restore pathogenicity and viral dissemination.At the same time, the strategy of polymerase fidelity modulation was explored as a novel approach for developing live virus vaccines in the poliovirus mouse model of infection. The same method was used to impede the establishment of a persistent infection which is the common problem for Coxsackie virus and heart disease. Collectively, the project findings underscored the potential of polymerase fidelity modulation as an alternative, safer vaccination approach. Given that virus population diversity is the main factor in immune evasion, the new methods of changing the genetic diversity and adaptability of RNA viruses are expected to have a significant impact in the field of vaccine development.
