Characterization and antiviral function of a cytosolic sensor gene, MDA5, in Japanese flounder, Paralichthys olivaceus

• Published in: Developmental and comparative immunology Vol. 35; no. 5; pp. 554 - 562
• Main Authors: Ohtani, Maki, Hikima, Jun-ichi, Kondo, Hidehiro, Hirono, Ikuo, Jung, Tae-Sung, Aoki, Takashi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 01-05-2011
• Subjects: Animals; Antiviral activity; cytopathogenicity; Cytoplasm; Embryos; Fish Proteins - genetics; Fish Proteins - immunology; flounder; Flounder - genetics; Flounder - immunology; Flounder - virology; Gene Expression; genes; Hemorrhagic septicemia; Hirame rhabdovirus; Infection; Infectious pancreatic necrosis; Infectious pancreatic necrosis virus; Japanese flounder; Kidney; kidneys; Leukocytes; MDA5; Melanoma; Novirhabdovirus; Nucleotides; Organ Specificity; Paralichthys olivaceus; Pattern recognition; Peripheral blood; Phylogeny; Pleuronectiformes; Poly I:C; receptors; Receptors, Retinoic Acid - genetics; Receptors, Retinoic Acid - immunology; RNA; Transcription; VHSV; Viral hemorrhagic septicemia virus; viral load; Japanese flounder; Poly I:C; VHSV; Antiviral activity; MDA5
• ISSN: 0145-305X; 1879-0089
• DOI: 10.1016/j.dci.2010.12.013

Cytosolic pattern recognition receptors such as retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) play an important role in sensing viral RNAs. The receptor encoded by melanoma differentiation-associated gene 5 (MDA5), an RLR, recognizes viral RNA in the cytoplasm and enhances antiviral response in host cells. The full-length MDA5 gene in Japanese flounder,
Paralichthys olivaceus was cloned and found to have 11,251 nucleotides. MDA5 transcript abundance was significantly increased in whole kidney infected with viral hemorrhagic septicemia virus (VHSV) as well as whole kidney and peripheral blood leukocytes stimulated with poly I:C
in vitro. Hirame natural embryo (HINAE) cells overexpressing MDA5 showed a lower cytopathic effect (CPE) against VHSV, hirame rhabdovirus (HIRRV) and infectious pancreatic necrosis virus (IPNV) infection. When infected with VHSV, MDA5-overexpressing HINAE cells had 24–75 fold lower virus titer than normal HINAE cells. These results suggest that Japanese flounder MDA5 is involved in the induction of antiviral response.