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Quantification of intrahost genetic diversity of Piscine Orthoreovirus (PRV-1) infecting Atlantic and Chinook salmon

University of British Columbia

The decline in populations of wild Pacific salmon is of great concern given their importance to Indigenous Peoples of Canada, Pacific Northwest ecosystems, and commercial fisheries. Contagious diseases may contribute to these losses. Piscine orthoreovirus 1 (PRV-1) is a pathogen recently linked to Heart and Skeletal Muscle Inflammation (HSMI) in farmed British Columbian Atlantic salmon (Salmo salar), and jaundice/anemia in Chinook salmon (Oncorhynchus tshawytscha). Characterizing the genetic diversity of PRV-1 is foundational to understanding its relationship with salmon disease. PRV-1 is an RNA virus, and as such undergoes error-prone replication that leads to high mutation rates and pathogenic capacity. Reoviruses (respiratory enteric orphan viruses) are intermittently associated with diseases in a broad number of hosts including reptiles, birds, and humans, where their ability to trigger targeted host immune response is being exploited for oncolytics. While genetic differences in the majority proportion of a viral population infecting an individual host are captured at the consensus level, it is possible that minority mutations with equal or greater epidemiological effects can remain undetected. For this reason, it is important to quantify not only the genetic diversity of viral populations across hosts, but also within hosts. This study analyzes sequences of 102 samples from various PRV-1 positive tissues and blood of BC Atlantic, Chinook, and coho (Oncorhynchus kisutch) salmon spanning 7 years and 43 geographical locations, using high-throughput sequencing (HTS) and bioinformatic approaches. Results demonstrate intrahost viral genetic variation with the majority of mutations being nonsynonymous. Analysis of within-host genetic diversity revealed significant differences in the genome segments S1 and L2 encoding the cytotoxic protein and capping enzyme, respectively. Together, within and among host analysis showed loci with increased genetic diversity in the cytotoxic and attachment encoding segments. Additionally, a preliminary connection between patterns of elevated within host genetic diversity and persistent HSMI was observed, that could serve as an indicator of disease. Analysis among hosts also revealed a genetically distinct PRV-1 variant circulating in wild Columbia River Chinook salmon. The results presented in this thesis provide an example of how and why considering different scales of reovirus genetic diversity can inform host health.

Text

2022-01-31

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/76959

Microbiology and Immunology

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/