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.

Shedding Kinetics of Infectious Hematopoietic Necrosis Virus (IHNV) in Juvenile Spring- and Fall-Run Chinook Salmon of the Columbia River Basin

“…We found similar kinetics of shedding for all three IHNV strains in both Chinook salmon populations, with a rapid peak by 2–3 dpe, followed by a decline to levels below detection by 7 dpe. These results are consistent with the rapid kinetics reported for M viruses in rainbow trout [ 13 , 14 ]. This suggests that IHNV shedding kinetics may be a consistent phenotype for viruses from different genogroups and in different host species that co-evolved in the field under different conditions.…”

“…Their summary was that “viral shedding for IHNV is a very acute process that begins with a rapid peak after exposure to virus and tapers off quickly to a post-peak period of lower shedding magnitude that can extend for at least 12 days”. In a subsequent study they found very similar IHNV shedding kinetics for additional M genogroup strains in single and mixed infections of juvenile rainbow trout and reported a positive correlation between virulence and total shedding over a longer infection course of 30 days [ 14 ]. These first two studies defined consistent shedding kinetics for several M IHNV strains in rainbow trout, and the authors noted that “expanded studies with different IHNV genotypes and different hosts will be essential to assess if shedding kinetics is a variable viral phenotype” [ 13 ].…”

“…Viral challenges and subsequent monitoring were conducted at a constant water temperature of 10 °C to mimic average conditions observed throughout the CRB [ 20 ]. To assess the shedding kinetics of IHNV in spring- and fall-run Chinook salmon, juvenile fish (1 g) from each host population were exposed to L, UC and MD strains of IHNV and held in individual tanks for collection of shed virus samples over time as previously described [ 13 , 14 ]. For each host type 30 fish were exposed to each virus strain by static immersion for 1 h in 1 L of water containing virus at a dose of 2 × 10 5 plaque forming units (PFU) mL −1 .…”

“…A constant temperature of 10 °C was maintained by circulating temperature-controlled water around the tanks. Following the 23 h static period, water was sampled from each tank and flow was then turned on for 1 h to flush out any shed virus in the water [ 13 , 14 ]. Cycles of 23 h of static hold, followed by water sampling, and then a 1 h flush in flowing water were repeated daily, and samples were collected 0, 1, 2, 3, 4, 5, 7, 8, 10, 14, 22, and 30 days’ post exposure (dpe).…”

“…Virus shedding has been used as a proxy for virus transmission potential, and an assay to quantify the shedding kinetics of IHNV from individual juvenile rainbow trout over the entire course of infection has been developed by Wargo and colleagues [ 13 ]. Shedding assays of several IHNV strains of varying virulence, in both single and mixed infections, have defined a remarkably consistent picture of IHNV shedding from infected rainbow trout as a process with a very rapid onset that peaks 2–3 days after exposure to virus and then wanes, often to levels that are undetectable by 5–7 days’ post-exposure (dpe) [ 13 , 14 ]. To date this assay has been applied to rainbow trout infected with M genogroup strains of IHNV.…”