Abstract
MicroRNAs (miRNAs) have important roles in post-transcriptional regulation of gene expression. During viral infection, viruses utilize hosts to enhance their replication by altering cellular miRNAs. The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway plays crucial roles in the antiviral responses. In this study, two miRNAs (miR-9041 and miR-9850) from Macrobrachium rosenbergii were found to promote white spot syndrome virus (WSSV) replication. The up-regulation of miR-9041 or miR-9850 suppresses STAT expression in the gills of M. rosenbergii, which subsequently down-regulates the expression of its downstream dynamin (Dnm) genes: Dnm1, Dnm2, and Dnm3. Knockdown of miR-9041 and miR-9850 restricts WSSV replication by up-regulating STAT and Dnm gene expression. The silencing of STAT, Dnm1, Dnm2, or Dnm3 led to an increase of the number of WSSV copies in shrimp. The injection of recombinant Dnm1, Dnm2, or Dnm3 proteins could inhibit WSSV replication in vivo. Overall, our research indicates the roles of host miRNAs in the enhancement of WSSV replication by regulating the host JAK/STAT pathway.
Highlights
The giant fresh water prawn, Macrobrachium rosenbergii, has become an important cultured species in China and other southern East Asian countries[1,2]
Our research describes the roles of host miRNAs in enhancing white spot syndrome virus (WSSV) replication by regulating the host Janus kinase (JAK)/STAT pathway
The results showed that the fluorescence intensity in the co-transfected cells was significantly reduced compared with the intensity in the enhanced green fluorescent protein (EGFP)-STAT-transfected cells (Fig. 2C,F), thereby indicating that the synthesized miR-9041 or miR-9850 mimic repressed the expression of the STAT gene by targeting its 3′-untranslated region (UTR)
Summary
The giant fresh water prawn, Macrobrachium rosenbergii, has become an important cultured species in China and other southern East Asian countries[1,2]. Infectious viruses induce the production of interferons, interleukins, and growth factors, among others[14] These compounds are recognized by cytokine receptors, which activate the JAK/STAT pathway and leads to the transcription of interferon-inducible genes with antiviral functions[15]. In Culex mosquitoes, the activation of the JAK/STAT pathway can induce the expression of Vago, which is regarded as an antiviral factor, to restrict the West Nile virus infection[17]. More miRNAs have been shown to participate in innate and adaptive immune response during virus infection by regulating the viral or host gene expression[30]. The Epstein–Barr virus (EBV)-encoded viral miR-BART22 modulates the viral gene product expression of the EBV latent membrane protein 2A (LMP2A), which may facilitate nasopharyngeal carcinoma carcinogenesis by evading the host immune response[31]. The host miRNA-mediated regulations of the STAT gene and its downstream genes have not been well studied in the giant freshwater prawn to date
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