Abstract

MicroRNAs are regulatory molecules that can be packaged into exosomes to modulate cellular response of recipients. While the role of exosomes during viral infection is beginning to be appreciated, the involvement of exosomal miRNAs in immunoregulation in invertebrates has not been addressed. Here, we observed that exosomes released from WSSV-injected mud crabs could suppress viral replication by inducing apoptosis of hemocytes. Besides, miR-137 and miR-7847 were found to be less packaged in mud crab exosomes during viral infection, with both miR-137 and miR-7847 shown to negatively regulate apoptosis by targeting the apoptosis-inducing factor (AIF). Our data also revealed that AIF translocated to the nucleus to induce DNA fragmentation, and could competitively bind to HSP70 to disintegrate the HSP70-Bax (Bcl-2-associated X protein) complex, thereby activating the mitochondria apoptosis pathway by freeing Bax. The present finding therefore provides a novel mechanism that underlies the crosstalk between exosomal miRNAs and apoptosis pathway in innate immune response in invertebrates.

Highlights

  • Exosomes are extracellular vesicles of endocytic origin that are released into the extracellular environment under physiological and pathological conditions [1, 2]

  • We identified the miRNAs packaged by exosomes that were possibly involved in White spot syndrome virus (WSSV) infection by mediating hemocytes apoptosis in crustacean mud crab Scylla paramamosain

  • The results revealed that exosomes released from WSSV-injected mud crabs could suppress viral replication by inducing hemocytes apoptosis

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Summary

Introduction

Exosomes (measuring 30–120 nm in diameter) are extracellular vesicles of endocytic origin that are released into the extracellular environment under physiological and pathological conditions [1, 2]. They can be produced by various types of donor cells and transferred to target cells, which serve as mediators during intercellular communications by transporting information cargo, including lipids, proteins, mRNAs and microRNAs (miRNAs) [3, 4]. Very little is known about how exosomes regulate host immune response and impact on viral infection

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