A general and biomedical perspective of viral quasispecies

Abstract

Viral quasispecies refers to the complex and dynamic mutant distributions (also termed mutant spectra, clouds, or swarms) that arise as a result of high error rates during RNA genome replication. The mutant spectrum of individual RNA virus populations is modified by continuous generation of variant genomes, competition and interactions among them, environmental influences, bottleneck events, and bloc transmission of viral particles. Quasispecies dynamics provides a new perspective on how viruses adapt, evolve, and cause disease, and sheds light on strategies to combat them. Molecular flexibility, together with ample opportunity of mutant cloud traffic in our global world, are key ingredients of viral disease emergences, as exemplified by the recent COVID-19 pandemic. In the present article, we present a brief overview of the molecular basis of mutant swarm formation and dynamics, and how the latter relates to viral disease and epidemic spread. We outline future challenges derived of the highly diverse cellular world in which viruses are necessarily installed.

Keywords: RNA viruses; complexity; defective genome; mutations; viral disease.

FIGURE 1.

Intrahost viral quasispecies, and their impact in epidemic and pandemic spread. (A) Schematic representation of mutant spectra. On the upper left, an infected individual is viewed as including multitudes of compartmentalized mutant distributions; in reality, they are of far larger population sizes than drawn in the picture for simplicity. On the right, genomes or subgenomic stretches are drawn as horizontal lines, and mutations are depicted as symbols on the lines. Assuming an average of five mutations per a 10,000 nt genome, the number of genomes without mutations is minimal; the number increases when shorter, subgenomic RNA stretches (length in nucleotides [nt] indicated in the upper boxes) are considered (lines not drawn to scale). The graphs below indicate the probability of occurrence of viral genomes with k mutations [p(k)] per genome or subgenomic RNA stretch (color code for RNA length in the inserted box), according to the Poisson distribution, assuming an average of five mutations per genome. A numerical example and the importance of the virus population size for exploration of the space of functionally relevant sequences are explained in the text. (B) Representation of the pandemic spread of a virus from infected to susceptible individuals. Mutant distributions, captured in population bottlenecks of different intensity (arrows), are the transmitted entities. The complexity of mutant spectra adds to the uncertainties inherent to modifications of virus behavior following expansions among susceptible individuals. For simplicity, in A and B we display only point mutations, but for some RNA viruses (particularly SARS-CoV-2), insertions, and more often deletions, also contribute to genomic and subgenomic RNA variations.