Stress-Induced Reversion to Virulence of Infectious Pancreatic Necrosis Virus in Naïve Fry of Atlantic Salmon (Salmo salar L.)

Abstract

We have studied stress-induced reversion to virulence of infectious pancreatic necrosis virus (IPNV) in persistently infected Atlantic salmon (Salmo salar L.) fry. Naïve fry were persistently infected with a virulent strain (T217A221 of major structural virus protein 2, VP2) or a low virulent (T217T221) variant of IPNV. The fry were infected prior to immunocompetence as documented by lack of recombination activating gene-1, T-cell receptor and B-cell receptor mRNA expression at time of challenge. The fish were followed over 6 months and monitored monthly for presence of virus and viral genome mutations. No mutation was identified in the TA or TT group over the 6 months period post infection. Six months post infection TA and TT infected groups were subject to daily stress for 7 days and then sampled weekly for an additional period of 28 days post stress. Stress-responses were documented by down-regulation of mRNA expression of IFN-α1 and concomitant increase of replication levels of T217T221 infected fish at day 1 post stress. By 28 days post stress a T221A reversion was found in 3 of 6 fish in the T217T221 infected group. Sequencing of reverted isolates showed single nucleotide peaks on chromatograms for residue 221 for all three isolates and no mix of TA and TT strains. Replication fitness of reverted (TA) and non-reverted (TT) variants was studied in vitro under an antiviral state induced by recombinant IFN-α1. The T217A221 reverted variant replicated to levels 23-fold higher than the T217T221 strain in IFN-α1 treated cells. Finally, reverted TA strains were virulent when tested in an in vivo trial in susceptible salmon fry. In conclusion, these results indicate that stress plays a key role in viral replication in vivo and can facilitate conditions that will allow reversion from attenuated virus variants of IPNV.

Infectious pancreatic necrosis virus (IPNV) strain with genetic properties associated with low pathogenicity at Finnish fish farms

“…Several factors affecting pathogenicity have been recorded, including environmental stress (Taksdal et al 1998), the strain of virus (Song et al 2005) and an inherited factor in host immunity (Ozaki et al 2001). It has been shown that a low pathogenic Genogroup 5 IPNV strain can demonstrate pathogenicity in persistently infected Atlantic salmon subjected to stress (Gadan et al 2013). Even though similar studies have not been performed with Genogroup 2 IPNV isolates, the recent introduction and rapid spread of Genogroup 2 IPNV in Finnish inland farms might be a cause of future disease outbreaks and pose a possible threat to the fish farming industry.…”

An Overview of Vaccination Strategies and Antigen Delivery Systems for Streptococcus agalactiae Vaccines in Nile Tilapia (Oreochromis niloticus)

“…Although reversion of avirulent strains to virulence has not been demonstrated for S. agalactiae live vaccines used in aquaculture, studies carried out for some fish pathogens have shown reversion of avirulent strains to virulence in infected fish subjected to stress [20]. Hence, it is likely that there are environmental and fish biological factors that could lead to reversion of avirulent strains to virulence of S. agalactiae live vaccines.…”

Environmental Viral Metagenomics Analyses in Aquaculture: Applications in Epidemiology and Disease Control

“…For example, in our studies we have shown that a few amino acids strategically located on the outer surface of the infectious pancreatic necrosis virus (IPNV) capsid account for virulence and immunogenicity properties of IPNV in Atlantic salmon (Song et al, 2005; Munang’andu et al, 2013; Mutoloki et al, 2013, 2016). We have shown that non-pathogenic strains can revert to virulence based on mutations of two amino acid substitutions on the surface capsid of IPNV rendering avirulent strains to become virulent when fish infected with none pathogenic strains are subjected to stress (Gadan et al, 2013). Hence, it is likely that other viruses could use similar mechanisms to evolve from avirulent to virulent strains in different aquatic organisms.…”