Abstract
Growing evidence has indicated that the innate immune system can be regulated by microRNAs (miRNAs). However, the mechanism underlying miRNA-mediated simultaneous activation of multiple immune pathways remains unknown. To address this issue, the role of host miR-12 in shrimp (Marsupenaeus japonicus) antiviral immune responses was characterized in the present study. The results indicated that miR-12 participated in virus infection, host phagocytosis, and apoptosis in defense against white spot syndrome virus invasion. miR-12 could simultaneously trigger phagocytosis, apoptosis, and antiviral immunity through the synchronous downregulation of the expression of shrimp genes [PTEN (phosphatase and tensin homolog) and BI-1(transmembrane BAX inhibitor motif containing 6)] and the viral gene (wsv024). Further analysis showed that miR-12 could synchronously mediate the 5′–3′ exonucleolytic degradation of its target mRNAs, and this degradation terminated in the vicinity of the 3′ untranslated region sequence complementary to the seed sequence of miR-12. Therefore, the present study showed novel aspects of the miRNA-mediated simultaneous regulation of multiple immune pathways.
Highlights
During virus infection, multiple immune pathways are employed by hosts to defend against virus invasion [1]
The results showed that miR-12 overexpression led to significant decreases in white spot syndrome virus (WSSV) copies in shrimp compared with the controls (WSSV, WSSV + miR-12-scrambled and WSSV + AMO-miR-12-scrambled) (Figure 1C)
When miR-12 expression was inhibited by AMOmiR-12 (Figure 1B), the WSSV copies were dramatically increased compared with the controls (Figure 1C), indicating that miR-12 played a negative role in the virus infection
Summary
Multiple immune pathways are employed by hosts to defend against virus invasion [1]. Studies have shown that phagocytosis is required for host antiviral immunity through the direct rapid engulfment of virions and apoptotic cells [2,3,4]. Rab protein, which directly interacts with actin, is essential for the correct conformation of actin, showing a critical effect on phagocytosis against virus infection [4]. A series of signaling pathways can be triggered in the host, leading to apoptosis of infected cells [6, 7]. Recent reports have shown that this PDZ-binding motif can protect virus-infected cells from apoptosis by directly disrupting the proapoptotic function of scribble, thereby inhibiting infected cell elimination by immune cells [10]. As key regulatory elements of gene expression, an individual microRNA (miRNA) possess multiple target genes involved in different signaling pathways [11, 12], implying that a miRNA may simultaneously trigger multiple antiviral pathways
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