Dietary treatment for BKD

Dr. Martin Chen (Northwest Indian Fisheries Commission) is conducting studies in Chinook salmon to determine the effective dietary fluoride and iodide levels which would provide protection against clinical bacterial kidney disease (BKD). BKD is caused by Renibacterium salmoninarum and is one of the most severe diseases affecting hatchery-reared Chinook salmon. There is no antibiotic which provides a lasting cure for the disease. Use of dietary supplements to prevent BKD could replace the use of erythromycin and other antibiotics with an effective and economical alternative. Two potential dietary supplements are fluoride and iodide which have been shown to provide some protection against BKD in rainbow trout and Atlantic salmon.

Disease susceptibility and resistance

Damien Barrett (Grad Student, Bartholomew Lab) is selectively crossing fish from resistant and susceptible stocks to create hybrid offspring. Some of these fish are resistant, and some are susceptible. Ceratonova shasta is a myxozoan parasite that causes significant mortality of salmon and trout in the Pacific Northwest. Resistance to the parasite varies between fish stocks with stocks either being highly resistant or highly susceptible. Mapping a population in this way will allow the regions of genome responsible for resistance to this important pathogen to be identified.

Engineering disease resistance

Dr. Thomas Chen and Professor Chun-Mean Lin (U. of Connecticut) successfully demonstrated that several families of transgenic rainbow trout, which harbor the antimicrobial peptide cercropin P1 gene, are highly pathogen resistant. Disease outbreaks caused by pathogen infection is one of the most serious bottlenecks in the aquaculture industry worldwide. Traditional strategies including vaccination, antibiotics and selection of disease resistant fish strains by traditional approaches have been used to control fish diseases. However, these strategies can have high economic costs, can lead to selection of antibiotic-resistant pathogens and still a lack of effective cures for viral infections remains. Resistance to these disease agents can be promoted through selective breeding and transgenic fish technology.

Chiou, P., Chen, M., Lin, C.M., Khoo, J., Larson, J., Holt, R., Leong, J.A., Thorgaard, G., and Chen, T.T. 2014. Production of homozygous transgenic rainbow trout with enhanced disease resistance. Marine Biotechnology, 16(3):299-308.

Han, Y., Lin, C., and Chen, T.T. 2018. RNA-Seq analysis of differentially expressed genes relevant to innate and adaptive immunity in cecropin P1 tansgenic rainbow trout (Oncorhynchus mykiss). BMC Genomics 19:760.

IHN oral vaccine

Lumen Bioscience, a Washington based biotechnology company, is developing an oral vaccine for Infectious Hematopoietic Necrosis Virus (IHNV) with funding from the USDA. The vaccine uses genetically modified spirulina which is an algae that is generally regarded as safe (GRAS). IHNV is an economic problem for producers of salmon and trout in the Pacific Northwest. Vaccines are already available for IHNV, however their use is compromised as it is costly, needs trained personnel, involves needles and tissue scarring which leads to a lower value of the seafood. A scaffolding has been developed in spirulina to trigger a response from the fish's immune system. The scaffold makes it look like a disease is present but would be non-infectious. AAHL staff are assisting this company with delivering the vaccine and testing its efficacy when fish are exposed to the virus.

Lumen Bioscience website 

Article on development of IHNV vaccine 

IHN virus – early vaccine development

Professor JoAnn Leong and Mark Engelking conducted much of the foundation work to develop the only approved DNA vaccine against Infectious Hematopoietic Necrosis Virus (IHNV). IHNV is one of the most destructive pathogens of salmon and trout in the Pacific Northwest. The virus is transmitted via direct contact or via a contaminated water source through mucus, feces, urine, and sperm. Signs of infection include swollen abdomen, anemia, and hemorrhaging near the fins and mouth. Glycoprotein from the isolated wild-type iHNV was purified and provided substantial protection to rainbow trout and Kokanee (O. nerka) against IHNV.

Engelking, H.M., and Leong, J.C. 1989. The glycoprotein of infectious hematopoietic necrosis virus elicits neutralizing antibody and protective responses. Virus Research, 13(3):213-230.

Alsonso, M. and Leong, J.A. 2013. Licensed DNA vaccines against infectious hematopoietic necrosis virus (IHNV). Recent Pat. DNA Gene Seq 7(1):62-65.

Koi herpes virus – treatment

Dr. Ling Jin (OSU Carlson College of Veterinary Medicine) is conducting studies to investigate a treatment against Koi Herpes Virus reactivation. KHV is a virus that infects ornamental koi and common carp worldwide. Like most herpesvirus infections, there is currently no cure for KHV. Infected fish can show gill lesions, sunken eyes, or a notched nose. Research is being conducted to discover drugs or treatments that can reduce or stop KHV reactivation and save show or pet koi. Currently, the Jin lab is investigating the histone demethylase inhibitor (ML 324) as a drug against KHV reactivation from latency in both in vitro and in vivo studies. In preparation.

Koi herpes virus and stress

Dr. Ling Jin (OSU Carlson College of Veterinary Medicine) investigated Koi Herpes Virus (KHV) to determine whether reduced dissolved O₂ level has a role in KHV reactivation during temperature stress. KHV is a virus that infects ornamental koi and common carp worldwide. Like most herpes virus infections there is currently no cure for KHV. Infected fish can show gill lesions, sunken eyes or a notched nose. KHV reactivation can occur under stress conditions, such as heat stress, poor water quality or injury, which can cause disease and transmit the infection to naive fish. KHV reactivation during shipping contributes to the major loss in koi industry and trade. Temperature, handling and blood sampling were all found to be triggers for KHV reactivation in the latently infected koi. The dissolved O₂ levels were not found to significantly affect KHV reactivation.

Lin, L., Chen, S., Russell, D.S, Löhr, c.V., Milston-Clements, R., Song, T., Miller-Morgan, T., and Jin, L. 2017 ??????????? 240.

Mucosal immunity to parasites

Laura Taggart-Murphy (Bartholomew Lab; Microbiology) investigated host immune response to the myxozoan parasite Ceratonova shasta in salmon and trout. Specifically, she was interested in the adaptive immune response in mucosal tissues as measured by lgT levels. IgT is an antibody found mainly in mucosal tissues (gut, skin) and is analogous to mammalian IgA. By depleting IgT-producing B-cells the fish, more was learned about the role of this antibody against infection with different genotypes of C. shasta. Some genotypes of C. shasta result in high mortality (e.g., genotype I and II) whereas infection by genotype 0 rarely results in death. These studies illustrated that increased levels of pro-inflammatory cytokines in genotype II infections may contribute to inflammation whereas less inflammation in genotype 0 infections may allow parasites to persist for years. IgT depletion decreased pathogen load and the adaptive immune response may not protect against mortality from C. shasta.