Mechanisms of viral emergence

Abstract

A number of virologic and environmental factors are involved in the emergence and re-emergence of viral disease. Viruses do not conservatively occupy a single and permanent ecological niche. Rather, due to their intrinsic capacity for genetic change, and to the evolvability of fitness levels, viruses display a potential to parasitize alternative host species. Mutation, recombination and genome segment reassortment, and combination of these molecular events, produce complex and phenotypically diverse populations of viruses, which constitute the raw material on which selection acts. The majority of emerging viral diseases of humans have a zoonotic origin. Sociologic and ecologic factors produce diverse and changing environments in which viral subpopulations have ample opportunities to be selected from intrinsically heterogeneous viral populations, particularly in the case of RNA viruses. In this manner, new human, animal and plant viruses have emerged periodically and, from all evidence, will continue to emerge. This article reviews some of the mechanisms that have been identified in viral emergence, with a focus on the importance of genetic variation of viruses, and on the general concept of biological complexity.

Figure 1.

Schematic representation of genomic variations and population dynamics of RNA viruses. (A) In infected hosts RNA viruses replicate as complex distributions of related genomes termed viral quasispecies. 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 [, , –, , , , , , , , , , , –61, 66, 71, 74].

Figure 2.

A simplified view of some events involved in RNA virus transmission, that takes into consideration that RNA viruses are quasispecies (mutant distributions). A swine-human transmission is used as illustration. An RNA virus replicates in an infected swine and it can shed different amounts of virus (a, b, c) that can reach a susceptible human. If two specific mutations are needed for the virus to initiate replication in the exposed human host, only the mutant spectrum that includes the required mutations will be established in the human host (in this case distribution b). If viral replication continues in the same individual (human figure on the right, two time points of the same human depicted as separated by the grey arrow), a new mutant distribution will be generated, shaped by the selective constraints imposed by each individual human (immune response and others). Human-to-human transmission (not shown in this scheme) will again involve bottlenecks of different intensities (number of genomes that reach the successive recipient humans). When transmissions occur among individuals of the same host species, it is likely that most mutant distributions will include genomes that are replication-competent in the recipient host. The picture is in reality more complex, as documented in the text. However, the scheme emphasizes the fact that viruses are not defined sequences but mutant distributions, and very frequently this pro-adaptive population structure has not been considered in treatments of emerging viral infections.