Characterization of infectious dose and lethal dose of two strains of infectious hematopoietic necrosis virus (IHNV)

Abstract

The ability to infect a host is a key trait of a virus, and differences in infectivity could put one virus at an evolutionary advantage over another. In this study we have quantified the infectivity of two strains of infectious hematopoietic necrosis virus (IHNV) that are known to differ in fitness and virulence. By exposing juvenile rainbow trout (Oncorhynchus mykiss) hosts to a wide range of virus doses, we were able to calculate the infectious dose in terms of ID50 values for the two genotypes. Lethal dose experiments were also conducted to confirm the virulence difference between the two virus genotypes, using a range of virus doses and holding fish either in isolation or in batch so as to calculate LD50 values. We found that infectivity is positively correlated with virulence, with the more virulent genotype having higher infectivity. Additionally, infectivity increases more steeply over a short range of doses compared to virulence, which has a shallower increase. We also examined the data using models of virion interaction and found no evidence to suggest that virions have either an antagonistic or a synergistic effect on each other, supporting the independent action hypothesis in the process of IHNV infection of rainbow trout.

Impact of Vaccination and Pathogen Exposure Dosage on Shedding Kinetics of Infectious Hematopoietic Necrosis Virus (IHNV) in Rainbow Trout

“…Because dosage increased the initial probability-but not duration-of shedding, this implies that immune clearance of the virus by fish operated at the same rate regardless of dosage. This suggests that increasing the dosage did not lead to suppression of the immune system and supports the independent action hypothesis of virus particles, as previously observed by McKenney et al (2016). However, the results imply that vaccine protection may operate under a threshold, wherein high viral dosages will overwhelm reductions in the probability of infection due to vaccination, and that these reductions are not absolute.…”

“…A few studies have investigated whether the increase in probability of infection with pathogen exposure dosage is a function of simply more virus particles entering the host (independent action) or virus particles interacting in some way to enhance infection (mass action), such as through suppression or overwhelming of the immune system (Regoes et al 2003;Zwart et al 2011). Previous studies in this system indicate an independent action mechanism, in that the increased probability of infection with dosage is not greater than expected since there are simply a large number of infectious particles present (McKenney et al 2016). However, these previous studies did not examine the duration of shedding, which could provide some insights into the nature of protection.…”

Reducing risks from coronavirus transmission in the home—the role of viral load

“…A model of African swine flu virus shows a clear dose-response relation between the infecting dose and disease in the animal 56. Likewise, a strong dose-response effect is found in the animal model for haemopoietic necrosis virus 6.…”

Masks Do More Than Protect Others During COVID-19: Reducing the Inoculum of SARS-CoV-2 to Protect the Wearer

“…9 There are two likely reasons for the effectiveness of facial masks: The first-to prevent the spread of viral particles from asymptomatic individuals to others-has received a great deal of attention. 10,11 However, the second theory-that reducing the inoculum of virus to which a mask-wearer is exposed will result in milder disease [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] -has received less attention and is the focus of our perspective which compiles virologic, epidemiologic and ecologic evidence.…”

“…Masks, depending on the material and design, filter out a majority of viral particles, but not all. 28 The theory that exposure to a lower inoculum or dose of any virus (whether respiratory, gastrointestinal or sexually transmitted) can make subsequent illness far less likely to be severe [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] has been propounded for some time. Indeed, the concept of the 50% lethal dose (LD50), the virus dose at which 50% of exposed hosts die, determined via controlled experiments in which a range of exposure doses are administered to animals to calculate a dose-mortality curve, was first described in 1938.…”