Zebrafish (Danio rerio) as a model for the study of vaccination against viral haemorrhagic septicemia virus (VHSV)

Novoa, B., Romero, A., Mulero, V., Rodriguez, I., Fernandez, I., and Figueras, A.
Vaccine   24(31-31): 5806-5816 (Journal)
Registered Authors
Figueras, Antonio, Novoa, Beatriz
Zebrafish, Vaccine, VHSV, Fish virus, Immune adaptive response, Cytokines
MeSH Terms
  • Animals
  • Disease Models, Animal*
  • Hemorrhagic Septicemia, Viral/immunology
  • Hemorrhagic Septicemia, Viral/pathology
  • Hemorrhagic Septicemia, Viral/prevention & control*
  • Novirhabdovirus/immunology
  • Vaccination/methods*
  • Viral Vaccines/immunology
  • Viral Vaccines/therapeutic use*
  • Zebrafish/immunology
  • Zebrafish/virology*
16777275 Full text @ Vaccine
The rhabdovirus viral haemorrhagic septicemia virus (VHSV) is the etiological agent of one of the most important salmonid viral diseases. In the present work, the ability of VHSV to infect and replicate in zebrafish at low temperature (15 degrees C) was demonstrated. Zebrafish was also used to determine the effectiveness of the recombinant virus rIHNV-Gvhsv GFP as a live attenuated vaccine against the virulent VHSV strain. Fish intraperitoneally injected with 3x10(6) to 3x10(5)TCID(50)/ml of the wild type VHSV showed a 100% of cumulative mortality, meanwhile only 57% of mortality was obtained in bath infections. Infected fish showed external clinical signs and histological observations revealed the appearance of small haemorrhages in the muscle, kidney, liver and dermis. Neither mortalities nor clinical signs were recorded in fish infected with a live attenuated recombinant virus. By RT-PCR technique, VHSV was detected in all the organs as early as 24h, but the recombinant virus was not detected in all the sampled days. VHSV was able to replicate "in vitro" in head kidney cells but the replication capacity of the attenuated viral strain was limited. The recombinant virus rIHNV-Gvhsv GFP was able to protect against VHSV with a survival rate ranging from 20% to 60% depending of the vaccine dose. The increase of TLR3, IFNalphabeta, Mx, IFNgamma and TNFalpha expression at 72h post-infection in the kidney of VHSV-infected fish contrasted with the results obtained with the avirulent virus, which did not induce an increment of this expression in infected fish. Zebrafish is a suitable animal model to study VHSV infection and immune (innate and adaptive) responses and, more importantly, we demonstrate for the first time the usefulness of the zebrafish as a vaccination model to viral diseases. In addition, the high protection obtained with the live attenuated virus demonstrates that the zebrafish is able to mount an efficient antiviral immune response at 15 degrees C.
Genes / Markers
Show all Figures
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes