Receptor complex and signalling pathway of the two type II IFNs, IFN-gamma and IFN-gamma rel in mandarin fish or the so-called Chinese perch Siniperca chuatsi

摘要

IFN-gamma, as the sole member of mammalian type II IFN, is a multifunctional cytokine which exerts its effects through two distinct IFN-gamma receptors, IFNGR1 and IFNGR2. However, in teleost fish, another IFN-gamma homologous gene, namely IFN-gamma related gene (IFN-gamma rel), has been identified. Although IFN-gamma and IFN-gamma rel genes have been described in some fish species, many important aspects remain poorly understood in relation with their signalling and function. In the present study, IFN-gamma and IFN-gamma rel, as well as their receptors, cytokine receptor family B (CRFB) 17, CRFB13, two of which are homologous to IFNGR1 in mammals, and CRFB6, homolomous to IFNGR2, have been characterized in mandarin fish, Siniperca chuatsi. It was revealed that the two type IFN members exhibit antiviral activity, and IFN-gamma transduces downstream signalling through CRFB13 and CRFB6, while IFN-gamma rel interacts with CRFB17 to activate downstream signalling. Moreover, IFN-gamma and IFN-gamma rel have been shown to exert antiviral biological activity in a STAT1-dependent manner. Intracellular domain analysis of CRFB17 and CRFB13 demonstrated that the Y386 tyrosine residue of CRFB13 is required for the activation of the IFN-gamma-mediated biologic response, and the Y324 and Y370 residues in CRFB17 are required to activate IFN-gamma rel signalling.