MiR-10c Facilitates White Spot Syndrome Virus Infection by Targeting Toll3 in Litopenaeus vannemei.

Hongliang Zuo,Mengting Luo,Zhiming Zhu,Jianguo He,Xinxin Liu,Linwei Yang,Xiaopeng Xu,Shaoping Weng

doi:10.3389/fimmu.2021.733730

Abstract

Toll-like receptors (TLRs) are canonical cell membrane receptors functioning to recognize pathogens and transduce signals to activate immune responses. It has been known that Toll3 in Pacific white shrimp Litopenaeus vannamei (LvToll3) plays a critical role in antiviral immunity by inducing the transcription of interferon regulatory factor (IRF), which mediates a signaling axis that is similar to the interferon system of vertebrates. However, the regulatory mechanism of the Toll3-IRF signaling is still unclear. In this study, a novel microRNA (miRNA) of miR-10 family, temporarily named as miR-10c, was identified from L. vannamei. miR-10c may play a nonnegligible regulatory role in shrimp immune responses since it was constitutively expressed in all detected tissues and transcriptionally induced by immune stimulation. Functional analysis validated that miR-10c could target LvToll3 to inhibit its expression, through which miR-10c blocked the nuclear translocation of IRF and facilitated white spot syndrome virus (WSSV) infection. To our knowledge, the present study revealed the first report of a Toll targeted by miRNA in crustaceans and provided a solid evidence base for supporting the role of LvToll3 in antiviral defense by activating IRF signaling in L. vannamei. Identification of the miR-10c/Toll3/IRF regulatory axis in shrimp provides new insights into the participation of miRNA in the regulation of immune responses and contributes to in-depth understanding of the mechanisms of Toll-induced immune responses in L. vannamei.

Highlights

Tolls/Toll-like receptors (TLRs) are one of the most common pathogen sensors in metazoans, recognizing diverse pathogens such as Gram-positive and Gram-negative bacteria, RNA or DNA viruses, fungi, and other protozoans in the early stage of host immune response [1]
We identified a novel miRNA from miR-10 family in L. vannemei and unveiled its regulatory role in shrimp antiviral immunity via targeting LvToll3 and further regulating interferon regulatory factor (IRF) expression
To investigate miRNA profiles of L. vannemei during the responses to virus, small RNAs were isolated from hemocytes at 4, 12, 24, and 48 h after the intramuscular injection of white spot syndrome virus (WSSV) and the miRNA libraries were constructed and sequenced on the Illumina HiSeq 2000 sequencing platform

Summary

Introduction

Tolls/Toll-like receptors (TLRs) are one of the most common pathogen sensors in metazoans, recognizing diverse pathogens such as Gram-positive and Gram-negative bacteria, RNA or DNA viruses, fungi, and other protozoans in the early stage of host immune response [1]. Tolls transduce signals into cells through various signal pathways to activate expression of a series of immune and inflammatory genes for the establishment of the immune activation state miR-10c Facilitates Virus Infection in the host [2]. There are 10 and 12 TLRs identified in humans and mice, respectively, in which TLR1, TLR2, TLR5, TLR6, and TLR10 are responsible for microbial lipid, polysaccharide, and protein recognition, while TLR3, TLR7, TLR8, and TLR9 are responsible for viral nucleic acid recognition [3, 4]. The number of Tolls/TLRs varies among different organisms. Stimulation of TLRs results in the activation of different intracellular signaling cascades, generally leading to the activation of NF-kB and activating protein-1 (AP-1) in MyD88dependent pathways and type I interferons (IFNs) in TRIFdependent antiviral pathways [8, 9]

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Conclusion