Contrasting selective patterns across the segmented genome of bluetongue virus in a global reassortment hotspot.

Maude Jacquot,Sushila Maan,Roman Biek,Kyriaki Nomikou,Peter Mertens,Sarita Yadav,Karam P Singh,Divakar Hemadri,Narasimha Reddy,Nagendra R Hegde,Y Krishna Jyothi,Pavuluri P Rao,Kalyani Putty,Narender Singh Maan

doi:10.1093/ve/vez027

Abstract

For segmented viruses, rapid genomic and phenotypic changes can occur through the process of reassortment, whereby co-infecting strains exchange entire segments creating novel progeny virus genotypes. However, for many viruses with segmented genomes, this process and its effect on transmission dynamics remain poorly understood. Here, we assessed the consequences of reassortment for selection on viral diversity through time using bluetongue virus (BTV), a segmented arbovirus that is the causative agent of a major disease of ruminants. We analysed ninety-two BTV genomes isolated across four decades from India, where BTV diversity, and thus opportunities for reassortment, are among the highest in the world. Our results point to frequent reassortment and segment turnover, some of which appear to be driven by selective sweeps and serial hitchhiking. Particularly, we found evidence for a recent selective sweep affecting segment 5 and its encoded NS1 protein that has allowed a single variant to essentially invade the full range of BTV genomic backgrounds and serotypes currently circulating in India. In contrast, diversifying selection was found to play an important role in maintaining genetic diversity in genes encoding outer surface proteins involved in virus interactions (VP2 and VP5, encoded by segments 2 and 6, respectively). Our results support the role of reassortment in driving rapid phenotypic change in segmented viruses and generate testable hypotheses for in vitro experiments aiming at understanding the specific mechanisms underlying differences in fitness and selection across viral genomes.

Highlights

RNA viruses have an extraordinary ability to diversify and evolve
Repeating the BEAST analysis after excluding the Bluetongue virus (BTV)-10 sequences brought the coefficients of variation (CoV) for the clock rate down for five of the ten segments but this had a negligible effect on their TRMCA estimates (Supplementary Table S3)
Our findings confirm that genetic exchange by reassortment has had a major impact on the genomic composition of Indian BTV strains

Summary

Introduction

RNA viruses have an extraordinary ability to diversify and evolve. The observed high evolution rate of RNA viruses is partly attributed to limited or no proof reading capacity of RNA-dependent RNA polymerases. For viruses with segmented genomes, rapid genomic and phenotypic changes can occur through the process of reassortment, whereby coinfecting different viral strains exchange entire segments (see McDonald et al 2016 for a review). This has received considerable research attention in certain groups, such as influenza viruses, where reassortment has been linked to changes in host range and the emergence of novel strains (e.g. Li et al 2004; Schweiger, Bruns, and Meixenberger 2006; Simonsen et al 2007; Nelson et al 2008; Rambaut et al 2008; Smith et al 2009; Trifonov et al 2009; Wu et al 2015; Pohlmann et al 2017). Bluetongue virus (BTV) belongs to the genus Orbivirus of the family Reoviridae. In the USA for example, BTV is thought to cause losses in the order of US$125 million annually (Tabachnick 1996)

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