Mechanisms of viral emergence

Domingo, Esteban

Very few topics in Virology relate so closely to the general concept of biological complexity as the emergence and re-emergence of viral disease. In the introduction to their classic book, Solé and Goodwin define the sciences of complexity as ''the study of those systems in which there is no simple and predictable relationship between levels, between the properties of parts and of wholes'' [78] . The emergence of viral disease involves several levels of complexity. The underlying level stems from the population structure of viral populations as they replicate in their standard hosts. Model studies of plaque-to-plaque transfers (bottleneck Here two out of multiple distributions are represented. Horizontal lines depict individual genomes and symbols on the lines represent different mutation types (transitions, transversions and short insertions or deletions termed indels). A distribution is defined by a consensus sequence and a mutant spectrum with a complexity given by the average pairwise genetic (also termed Hamming) distance among its components or the average mutation frequency. (B) Molecular recombination. (C) Genome segment reassortment, using influenza A virus (eight genomic segments) as an example. Reassortment (in this case the replacement of HA and NA genes) gives rise to an antigenic shift. Continued accumulation of mutations results in gradual antigenic drift. (D) A simplified view of quasispecies dynamics and fitness change. Unrestricted replication (large black arrow-head on the right, with multiple passages indicated by the dotted line) results in fitness gain, as depicted by the triangle at the bottom. Fitness gain can occur without variation of the consensus sequence (top). In contrast, repeated bottleneck transfers (left, with the dotted line representing multiple transfers) result in accumulation of mutations that modify the consensus sequences, and in fitness decrease. At low and high fitness values significant fluctuations of fitness values have been observed. This figure is based on previously published data and concepts [4, 9, 11-14, 16, 17, 19, 21, 25, 29, 31, 35, 41, 57, 59-61, 66, 71, 74] . passages) of foot-and-mouth disease virus (FMDV) in BHK-21 cells (Fig. 1) showed that the pattern of fitness decay of the virus followed a Weibull distribution [42] . This type of statistical distribution suggests that the mutations fixed in the viral genome at each transfer produced a cascade of perturbations in the virus-host interactions that were sensed in the form of a change in virus yield [42] . The unpredictability of the effect of mutations is further reinforced by the increasing evidence that viral proteins are multi-functional so that mutations can alter one or more of the interactions between viral and host components that determine the viral yield per cell [42] .