Detection of truncated virus particles in a persistent RNA virus infection in vivo

Abstract

Infectious hematopoietic necrosis virus (IHNV) is a rhabdovirus which causes devastating epizootics of trout and salmon fry in hatcheries around the world. In laboratory and field studies, epizootic survivors are negative for infectious virus by plaque assay at about 50 days postexposure. Survivors are considered virus free with no sequelae and, thus, are subsequently released into the wild. When adults return to spawn, infectious virus can again be isolated. Two hypotheses have been proposed to account for the source of virus in these adults. One hypothesis contends that virus in the epizootic survivors is cleared and that the adults are reinfected with IHNV from a secondary source during their migration upstream. The second hypothesis contends that IHNV persists in a subclinical or latent form and the virus is reactivated during the stress of spawning. Numerous studies have been carried out to test these hypotheses and, after 20 years, questions still remain regarding the maintenance of IHNV in salmonid fish populations. In the study reported here, IHNV-specific lesions in the hematopoietic tissues of rainbow trout survivors, reared in specific-pathogen-free water, were detected 1 year after the epizootic. The fish did not produce infectious virus. The presence of viral protein detected by immunohistochemistry, in viral RNA by PCR amplification, and in IHNV-truncated particles by immunogold electron microscopy confirmed the presence of IHNV in the survivors and provided the first evidence for subclinical persistence of virus in the tissues of IHNV survivors.

Defective Interfering Influenza Virus RNAs: Time To Reevaluate Their Clinical Potential as Broad-Spectrum Antivirals?

“…However, with the advent of genome amplification techniques, including most recently deep sequencing, putative defective and/or defective interfering genomes have been identified in a number of human infections, including those with dengue virus (17), hepatitis B virus (18), hepatitis C virus (19), hepatitis A virus (20), and influenza A virus (21). Defective genomes have also been isolated from hepatitis A virus-infected marmosets (20) and from infectious hematopoietic necrosis virus-infected trout (22). In addition, it appears likely that DI influenza A virus and DI dengue virus can be transmitted from person to person (21,23).…”

Low-Fidelity Polymerases of Alphaviruses Recombine at Higher Rates To Overproduce Defective Interfering Particles

“…Another curious feature of RNA virus replication is the production of truncated genomes and defective interfering particles (DIs). First reported in 1947 by von Magnus and later explored by Huang and Holland during the 70s and the 80s, DI production is now described in almost every RNA virus family (11)(12)(13)(14)(15)(16)(17)(18)(19). DIs are truncated forms of viral genomes that accumulate during replication, especially during passage in cell culture at a high multiplicity of infection (MOI).…”

Molecular biological tools to detect fish pathogens*

“…In summary, the molecular tools of PCR and immunogold-electron microscopy have provided evidence that a carrier state for IHNV exists in fish surviving an IHNV epizootic. In the study by Drolet et al (1995), the survivor and the control fish groups were sampled over a period of 2 years. The survivors remained positive for these assays during each sampling episode and the control fish remained negative during the same time periods.…”