Basis of host-specific virulence of U and M genogroup infectious hematopoietic necrosis virus (IHNV)

For the fish rhabdovirus infectious hematopoietic necrosis virus (IHNV), host-specificity of virus strains from the U and M genogroups has been established, wherein M genogroup IHNV isolates are more prevalent and more virulent than U genogroup IHNV isolates in rainbow trout ( Oncorhynchus mykiss). In this dissertation, we investigated the basis of host-specific virulence of U and M genogroup IHNV in rainbow trout in live infection challenges with representative U and M IHNV strains. Increase in mortality was observed when U IHNV was delivered by intraperitoneal injection rather than immersion, suggesting that the low virulence of U IHNV is partly due to inefficiency in entering into the fish host. In vivo replication studies showed that M IHNV consistently had higher prevalence and higher viral load that persisted longer than U IHNV during the course of infection. In vivo fitness assays also showed that M is more fit than U IHNV in rainbow trout, indicating a positive correlation between IHNV fitness and virulence. In analyses of the host immune response, M IHNV-infected fish consistently had higher and longer expression of innate and adaptive immune-related genes, suggesting that the higher virulence of M IHNV was not due to suppression of the trout immune response. The persistence of M IHNV in the presence of a stronger host immune response supported a kinetics hypothesis, wherein faster replication to higher levels enables M IHNV to withstand the rainbow trout immune response. The kinetics hypothesis was further supported by the decrease in M viral load and virulence in fish with pre-stimulated innate immune response after poly(I:C) injection. In addition, the viral load associated with virulence was lower for M than U IHNV. Taken together, we have identified entry into the fish host, in-host replication, and an inherent difference in the U and M IHNV viral load associated with virulence as multiple factors that contribute to the host-specific virulence of U and M IHNV in rainbow trout. In contrast, the host immune response does not play a significant role in this differential virulence despite susceptibility of both IHNV strains to IFN-mediated responses.