Virus shedding kinetics and unconventional virulence tradeoffs

Abstract

Tradeoff theory, which postulates that virulence provides both transmission costs and benefits for pathogens, has become widely adopted by the scientific community. Although theoretical literature exploring virulence-tradeoffs is vast, empirical studies validating various assumptions still remain sparse. In particular, truncation of transmission duration as a cost of virulence has been difficult to quantify with robust controlled in vivo studies. We sought to fill this knowledge gap by investigating how transmission rate and duration were associated with virulence for infectious hematopoietic necrosis virus (IHNV) in rainbow trout (Oncorhynchus mykiss). Using host mortality to quantify virulence and viral shedding to quantify transmission, we found that IHNV did not conform to classical tradeoff theory. More virulent genotypes of the virus were found to have longer transmission durations due to lower recovery rates of infected hosts, but the relationship was not saturating as assumed by tradeoff theory. Furthermore, the impact of host mortality on limiting transmission duration was minimal and greatly outweighed by recovery. Transmission rate differences between high and low virulence genotypes were also small and inconsistent. Ultimately, more virulent genotypes were found to have the overall fitness advantage, and there was no apparent constraint on the evolution of increased virulence for IHNV. However, using a mathematical model parameterized with experimental data, it was found that host culling resurrected the virulence tradeoff and provided low virulence genotypes with the advantage. Human-induced or natural culling, as well as host population fragmentation, may be some of the mechanisms by which virulence diversity is maintained in nature. This work highlights the importance of considering non-classical virulence tradeoffs. Whether pathogens evolve to cause more or less disease as they adapt to hosts is a long-standing question. Answering this question is a critical step in disease management because it allows for assessment of which emergent pathogens are likely to have devastating health impacts and which are not. Theory ascertains that pathogens should evolve to cause intermediate levels of disease, i.e. virulence, to their hosts. However, this theory is based on limited empirical evidence. We sought to evaluate various assumptions inherent in this theory. To do so we quantified how pathogen transmission (measured as viral shedding) is associated with virulence (measured as host mortality), in a virus that heavily impacts salmon aquaculture and conservation. We found that there were both fitness costs and benefits of virulence for the virus, but the benefits typically outweighed the costs, resulting in selection for increased virus virulence. We did, however, identify scenarios where less virulent virus strains could have the evolutionary advantage. This work provides important insights into virulence evolution and how it might be managed so as to reduce long-term disease impacts.