Fundamentals of molecular Virology An introduction to molecular virology

Molecular virology has developed very important tools to dissect viral functions by engineering infectious molecular clones with preselected modifications. The derivations of reverse genetics first developed by C. Weissmann with the bacteriophage Qβ systemhave permeated virology to the point that, with the exception of a few viruses, reverse genetics has been applied to most of them, be they RNA or DNA viruses. Here fitness comes as a relevant parameter concerning the difference between a virus having the attribute of "viable" as such versus "viable" for evolutionary success. At least part of the constructs that are currently investigated with viruses (numerous and readily accessible to any literature search) yield infectious viruses that will have only a minimal chance to survive in an evolutionarily competitive scenario. What an infectious construct tells us is that basic functional performance of a virus is operating, and this is extremely informative of the basic molecular requirements for a virus to express minimally its replicative program. We should be aware, however, that an infectious construct may be too debilitated to have prospects of its being established as a competitive biological element in nature or even in cell culture or in ex vivo experiments. In support of this assertion is the fact that replication of many such constructs leads to variant form that display fitness increases and that have accumulated multiple mutations in their genomes. Such fitness optimization through accumulation of mutations is observed with entire viruses and subgenomic replicons. The advantage conferred by a mutant spectrum over its individual components may be one of the reasons of poor performance of specific constructs. Therefore, what is functional biochemically or in a single round of infection may be nonfunctional from the point of view of evolutionary prospects.