RGNNV induces mitochondria-mediated cell death via newly synthesized protein dependent pathway in fish cells

Horng Cherng Wu, Jen Leih Wu, Heuy Ling Chu, Yu Chin Su, Jiann Ruey Hong

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)


The RNA nervous necrosis virus induces necrotic cell death in fish; however, the molecular mechanism remains unknown. In this study, we demonstrated that beta-nodavirus-induced mitochondria-mediated dependent cell death is through newly synthesized protein dependent pathway in replication cycle. We determined that newly synthesized protein dependent pathway is required for red-spotted grouper nervous necrosis virus (RGNNV)-induced cell death. UV irradiation of the virus effectively blocked viral replication and cell death. Next, RGNNV RNA-dependent RNA polymerase (RdRp or protein A) was cloned and its involvement in RNA genome replication and viral protein synthesis was analyzed. Protein A was initially expressed 48 h post-infection and localized to the cytoplasm. Knockdown of protein A expression completely blocked viral genomic replication and expression of viral protein expression RNA1 small hairpin RNA (shRNA) producing cell lines, which coincided with inhibition of phosphatidylserine exposure, mitochondria-mediated death signaling, and increased cell viability 72 h post-infection. Furthermore, RGNNV-induced mitochondria-mediated caspase-3-independent necrotic cell death is dependent on viral synthesized protein dependent pathway at the middle-late replication stage. Taken together, for instance these results suggested that RGNNV induces cell death may require newly synthesized protein for triggering host mitochondria-mediated cell death. These findings may provide new insights into RNA viral pathogenesis.

Original languageEnglish
Pages (from-to)451-463
Number of pages13
JournalFish and Shellfish Immunology
Issue number3
Publication statusPublished - 2010 Sept

All Science Journal Classification (ASJC) codes

  • Environmental Chemistry
  • Aquatic Science


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