Evaluating the potential of whole-genome sequencing for tracing transmission routes in experimental infections and natural outbreaks of bovine respiratory syncytial virus

Johnson, P. C. D. , Hägglund, S., Näslund, K., Meyer, G., Taylor, G., Orton, R. J. , Zohari, S., Haydon, D. T. and Valarcher, J. F. (2022) Evaluating the potential of whole-genome sequencing for tracing transmission routes in experimental infections and natural outbreaks of bovine respiratory syncytial virus. Veterinary Research, 53, 107. (doi: 10.1186/s13567-022-01127-9) (PMID:36510312) (PMCID:PMC9746130)

Abstract

Bovine respiratory syncytial virus (BRSV) is a major cause of respiratory disease in cattle. Genomic sequencing can resolve phylogenetic relationships between virus populations, which can be used to infer transmission routes and potentially inform the design of biosecurity measures. Sequencing of short (<2000 nt) segments of the 15 000-nt BRSV genome has revealed geographic and temporal clustering of BRSV populations, but insufficient variation to distinguish viruses collected from herds infected close together in space and time. This study investigated the potential for whole-genome sequencing to reveal sufficient genomic variation for inferring transmission routes between herds. Next-generation sequencing (NGS) data were generated from experimental infections and from natural outbreaks in Jämtland and Uppsala counties in Sweden. Sufficient depth of coverage for analysis of consensus and sub-consensus sequence diversity was obtained from 47 to 20 samples respectively. Few (range: 0–6 polymorphisms across the six experiments) consensus-level polymorphisms were observed along experimental transmissions. A much higher level of diversity (146 polymorphic sites) was found among the consensus sequences from the outbreak samples. The majority (144/146) of polymorphisms were between rather than within counties, suggesting that consensus whole-genome sequences show insufficient spatial resolution for inferring direct transmission routes, but might allow identification of outbreak sources at the regional scale. By contrast, within-sample diversity was generally higher in the experimental than the outbreak samples. Analyses to infer known (experimental) and suspected (outbreak) transmission links from within-sample diversity data were uninformative. In conclusion, analysis of the whole-genome sequence of BRSV from experimental samples discriminated between circulating isolates from distant areas, but insufficient diversity was observed between closely related isolates to aid local transmission route inference.

• Item Type: Articles
• Additional Information: Funding: This project was funded by the Swedish Research Council (Formas, Sweden), grant no. 2016–00463. Some samples were collected through funding from the European Union’s Horizon 2020 Program for research, technological development, and demonstration under the Grant Agreement n633184 (Project’s name SAPHIR), or from the Swedish Research Council (Formas, Sweden), the Biotechnology and Biological Sciences Research Council (BBSRC, UK) and L’Agence Nationale de la Recherche (ANR, France), through the Emerging and Major Infectious Diseases of Livestock (EMIDA) project in the European Research Area Network (ERA-NET), grant no. FP#87.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Johnson, Dr Paul and Haydon, Professor Daniel and Orton, Dr Richard
• Authors: Johnson, P. C. D., Hägglund, S., Näslund, K., Meyer, G., Taylor, G., Orton, R. J., Zohari, S., Haydon, D. T., and Valarcher, J. F.
• College/School: College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine; College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
• Journal Name: Veterinary Research
• Publisher: BioMed Central
• ISSN: 0928-4249
• ISSN (Online): 1297-9716
• Copyright Holders: Copyright © The Author(s) 2022
• First Published: First published in Veterinary Research 53: 107
• Publisher Policy: Reproduced under a Creative Commons License
• Data DOI: 10.5525/gla.researchdata.1287