RIG-I specifically mediates group II type I IFN activation in nervous necrosis virus infected zebrafish cells

Characterization of the IFN pathway in the teleost fish gonad against vertically transmitted viral nervous necrosis virus

“…This fact would suggest a high IFN or antiviral response in the sea bass gonad and a very low response in the brain, which could explain the low resistance of this fish species, but this needs to be confirmed at functional level. These results are in agreement with other studies in fish showing the upregulation of most of these genes after virus infection in several tissues or their antiviral function after cell line overexpression (Biacchesi et al, 2009;Chen et al, 2015;Feng et al, 2011;Rise et al, 2008Rise et al, , 2010Skjesol et al, 2011;Su et al, 2010;Sun et al, 2011;Xiang et al, 2011;Yang et al, 2011), and support the fact that the sequences identified in our study mediate the IFN activation cascade. In the case of tbk1, which is also activated by the TLR response, it is only upregulated in sea bass specimens infected with VNNV.…”

“…In contrast, in the European sea bass, inhibition of brain expression of ifn, as with most of those genes involved in the induction cascade, was concomitant with an increase in the transcription of mx and pkr. All the data point to the existence of other activation pathways in fish, as suggested previously (Feng et al, 2014) and demonstrated in ZF-4 cells in which the involvement of the TLR activation pathway is evidenced after VNNV infection (Chen et al, 2015). In addition, pkr is designed as an ISG, but it is able to directly recognize and bind to viral RNA, and therefore might be considered as another PRR.…”

“…In a similar manner, mda5 and lgp2 genes have been identified in all teleost fish studied so far, although the presence of rig1 is limited to ancient fish and has never been identified in modern fish (class Acanthopterygii) (Aoki et al, 2013), in which our fish species are included. Our data showed that the expression level of mda5 was upregulated in the SAF-1 cell line, which supports VNNV replication (Bandín et al, 2006), in a similar way to the zebrafish ZF-4 cell line, which also supports VNNV replication, in which rig1, mda5 and lgp2 transcription was upregulated by VNNV infection (Chen et al, 2015). However, neither mda5 nor lgp2 was altered in the newly obtained sea bass DLB-1 cells, in contrast to the situation with polyI: C stimulation.…”

“…Moreover, fish rig1 and mda5 transient overexpression leads to the induction of ifn expression and confers an antiviral state (Biacchesi et al, 2009;Sun et al, 2011). Very recently, in addition, rig1 knock-down in ZF-4 cells has demonstrated the importance of the group II type I IFN pathway in VNNV infections (Chen et al, 2015). However, lgp2 overexpression can produce both inducing and inhibitory effects on ifn expression, as evidenced in fish and mammals (Komuro & Horvath, 2006;Ohtani et al, 2012;Sun et al, 2011), probably due to the lack of the CARD domain, which is only present in RIG-I and MDA5 proteins.…”

“…This family has three members: RIG-I (also known as DDX58), melanoma differentiation-associated gene 5 (MDA5, also known as IFIN1) and Laboratory of Genetics and Physiology 2 (LGP2, also known as DHX58). These sensors are upregulated by Viral hemorrhagic septicemia virus (VHSV), Spring viremia of carp virus, Grass carp reovirus (GCRV; Aquareovius C), Viral nervous necrosis virus (VNNV; members of the genus Betanodavirus) and Infectious pancreatic necrosis virus (IPNV), as well as by polyinosinic acid (polyI: C; a synthetic analogue of viral dsRNA), leading to an increase in the IFN-mediated antiviral response (Chen et al, 2015;Feng et al, 2011;Rise et al, 2008Rise et al, , 2010Skjesol et al, 2011;Su et al, 2010;Yang et al, 2011). However, further studies are needed to definitely define their roles in the antiviral response, and to identify and characterize their mediators in the molecular pathway leading to IFN activation.…”