Population Structure and Evolution of Rhinoviruses

Abstract

Rhinoviruses, formerly known as Human rhinoviruses, are the most common cause of air-borne upper respiratory tract infections in humans. Rhinoviruses belong to the family Picornaviridae and are divided into three species namely, Rhinovirus A, -B and -C, which are antigenically diverse. Genetic recombination is found to be one of the important causes for diversification of Rhinovirus species. Although emerging lineages within Rhinoviruses have been reported, their population structure has not been studied yet. The availability of complete genome sequences facilitates study of population structure, genetic diversity and underlying evolutionary forces, such as mutation, recombination and selection pressure. Analysis of complete genomes of Rhinoviruses using a model-based population genetics approach provided a strong evidence for existence of seven genetically distinct subpopulations. As a result of diversification, Rhinovirus A and -C populations are divided into four and two subpopulations, respectively. Genetically, the Rhinovirus B population was found to be homogeneous. Intra-species recombination was observed to be prominent in Rhinovirus A and -C species. Significant evidence of episodic positive selection was obtained for several sites within coding sequences of structural and non-structural proteins. This corroborates well with known phenotypic properties such as antigenicity of structural proteins. Episodic positive selection appears to be responsible for emergence of new lineages especially in Rhinovirus A. In summary, the Rhinovirus population is an ensemble of seven distinct lineages. In case of Rhinovirus A, intra-species recombination and episodic positive selection contribute to its further diversification. In case of Rhinovirus C, intra- and inter-species recombinations are responsible for observed diversity. Population genetics approach was further useful to analyze phylogenetic tree topologies pertaining to recombinant strains, especially when trees are derived using complete genomes. Understanding of population structure serves as a foundation for designing new vaccines and drugs as well as to explain emergence of drug resistance amongst subpopulations.

Global epidemiology of non-influenza RNA respiratory viruses: data gaps and a growing need for surveillance

“…For rhinoviruses, the expansion of the small amount of complete viral genome data available-only around 200 full genomes are available compared with over 5000 for influenza A H1N1 pdm09 and over 6000 for influenza A H3N2-is essential to understand further the natural genetic diversity of these viruses and underlying evolutionary forces (ie, viral gene mutation and recombination driven by selection pressure), as a foundation for designing new antiviral drugs and vaccines. [70][71][72] Research regarding coronavirus infections has been dominated by studies on severe acute respiratory syndromeassociated coronaviruses and Middle East respiratory syndrome-associated coronaviruses. However, the development of an antiviral drug that is effective against the coronavirus family as a whole will also be effective against the milder, but much more prevalent common cold viruses (eg, coronavirus OC43, 229E, NL63, and HKU1).…”

Challenges in developing a cross-serotype rhinovirus vaccine

“…The more recently discovered C species comprises a further 50-60 viruses, albeit as defined by genetic analyses only. Studies of HRV evolution further show that intra-species and inter-species recombination is common [20,21]. Additionally, sequencing of clinical isolates in paediatric populations show that a large number of distinct genotypes circulate within a community at any given time [22][23][24].…”

Analysis of Next-generation Sequencing Data in Virology - Opportunities and Challenges

“…Furthermore, usage of both the admixture and the linkage models (with burn-in of 20,000 and burn-length of 40,000) helped to resolve the role of recombination in diversification of subpopulations. In case of Rhinovirus A, intra-species recombination was common, whereas in case of Rhinovirus C, intra-and inter-species recombination were observed to cause diversity [82].…”

“…The ability of the admixture model to account for recombination has been used to analyse the extent of recombination and its role in determining the population structure of viruses such as Hepatitis B virus [81] and Rhinoviruses [82].…”