1.3.2. Virus variability and evolution

The second major characteristic of viruses, particularly important when designing molecular assays, is the ease and speed with which they can generate and maintain large amounts of molecular variability. The virus encoded RNA dependant RNA polymerase (RdRp), which facilitates genome replication, lacks proofreading and repair mechanisms causing a high mutation rate in RNA viruses. Therefore a virus is not so much an individual entity with a fixed genome, but rather a large ‘swarm’ of closely related variants, recombinants and other genetic oddities that are transmitted between individuals as a unit. There are two forces that shape the genetic identity of such a ‘mutant swarm’ (or ‘quasi-species’ as it is officially known):

  • Fierce competition between molecular variants for supremacy in a particular cell, host etc.
  • Functional co-operation between variants, where a temporarily disfavoured variant can remain within the quasi-species by ‘borrowing’ essential functions such as replication and packaging from the locally dominant variant.

The functional co-operation is an adaptive super-feature of viruses, since it allows a wide range of genetic diversity to persist within a quasi-species across time, hosts and environments. The true adaptive strength of a virus lies therefore more in the diversity within the swarm than in the evolutionary abilities of any one strain.

The importance of this variability for experimentation is in the design of diagnostic assays for virus detection. Serological assays, such as ELISA, are generally not affected by this variability which is mainly expressed at the nucleic acid level. However, nucleic acid assays, especially those based on the Polymerase Chain Reaction (PCR), are often very sensitive to microvariation at the nucleotide level, where even a single base-pair difference can be exploited for specific diagnosis. It is here therefore that supreme care must be taken to ensure that the assays developed for detecting viruses, or virus strains, are designed accurately and conservatively, to avoid non-detection due to assay inadequacy (see also section 12; “Quality Control”).