TRAF6 is a critical factor in fish immune response to virus infection

Abstract

Tumor necrosis factor receptor-associated factor 6 (TRAF6) is one of the key adaptor molecule in Toll-like receptor signal transduction that triggers downstream cascades involved in innate immunity. In our previous study, the molecular characteristics of EtTRAF6 (TRAF6 from Epinephelus tauvina), the tissue distributions, expression patterns after challenging with bacterial and viral pathogens were investigated. Here we identified EtTRAF6 as an important regulator of virus-triggered signaling pathway. Overexpression of EtTRAF6-ORF and truncated forms of EtTRAF6, including EtTRAF6-C (delete the MATH domain), EtTRAF6-N (delete the RING domain) and EtTRAF6-MATH, inhibited IFN-β activity strongly in grouper spleen (GS) cells. Overexpression of EtTRAF6 repressed virus-induced production of type I IFNs. When EtTRAF6 cotransfected with EcIRF3 or EcIRF7, EtTRAF6 inhibited IRF-induced activation of IFN-β. Over-expressed EtTRAF6 inhibited the transcription of SGIV genes significantly in GS cells. Although TRAF6 has a role in apoptosis regulation, it is not known if EtTRAF6 has any role in apoptosis regulation. Strikingly, when over-expressed in fathead minnow (FHM) cells, EtTRAF6 protected them from cell death induced by SGIV. Therefore, these results suggest that TRAF6 may play a critical role in their response to SGIV infection, through regulation of a cell death pathway that is common to fish and humans.

Keywords: Apoptosis; Epinephelus tauvina; Interferon; SGIV; TRAF6.