Melanoma differentiation‐associated gene 5 in zebrafish provoking higher interferon‐promoter activity through signalling enhancing of its shorter splicing variant

Peng Fei Zou,Jian Ping Fu,Na Na Xue,Shan Nan Chen,Jun Hua Li,Xue Qin Liu,Pin Nie,Ming Xian Chang

doi:10.1111/imm.12179

Abstract

Melanoma differentiation-associated gene 5 (MDA5) is one of the three members in the retinoic acid-inducible gene I-like receptor (RLR) family, which are cytoplasmic pathogen recognition receptors recognizing intracellular viruses. In the present study, MDA5 and its spliced shorter forms, named as MDA5a and MDA5b, were identified in zebrafish. MDA5a and MDA5b can be up-regulated in cell lines following the infection of a negative ssRNA virus, the spring viraemia of carp virus (SVCV), and an intracellular Gram-negative bacterial pathogen Edwardsiella tarda, implying that the RLR may also be able to sense elements released from bacteria. The over-expression of MDA5a and MDA5b in fish cells resulted in significant induction of type I interferon promoter activity and enabled the protection of transfected cells against SVCV infection. Furthermore, the shorter spliced form, MDA5b when co-transfected with MDA5a or mitochondrial antiviral signalling protein (MAVS), induced a significantly higher level of interferon promoter activity, indicating that MDA5b may function as an enhancer in the interaction between MDA5 and MAVS.

Highlights

The innate immune defence against pathogenic invasion is mediated through the recognition of conserved pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors (PRRs)
MDA5a and MDA5b can be up-regulated in cell lines following the infection of a negative ssRNA virus, the spring viraemia of carp virus (SVCV), and an intracellular Gram-negative bacterial pathogen Edwardsiella tarda, implying that the retinoic acid-inducible gene I-like receptor (RLR) may be able to sense elements released from bacteria
The over-expression of MDA5a and MDA5b in fish cells resulted in significant induction of type I interferon promoter activity and enabled the protection of transfected cells against SVCV infection

Summary

Introduction

The innate immune defence against pathogenic invasion is mediated through the recognition of conserved pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors (PRRs). RIG-I and MDA5 may both functionally sense a diverse range of negative-stranded or positive-stranded RNA viruses.[15,16,17] Recently, it was reported that RIG-I and MDA5 may sense bacterial RNA or DNA released from the pathogenic bacterium Listeria monocytogenes to trigger the production of IFN-b and interleukin-1b.18

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Discussion

Conclusion