Abstract
In innate immunity, LGP2 (laboratory of genetics and physiology 2) plays a very important role in the production of type I interferon (IFN) through recognition of cytosolic viral RNA. Although viral infection or stimulation with double-strand RNA dramatically induces expression of the LGP2 gene, the underlying transcriptional mechanism has never been studied. Here, we cloned and characterized the 5′-upstream region (−1,337 bp) of the LGP2 gene in olive flounder (Paralichthys olivaceus). Numerous canonical motifs for IFN-regulatory factors (IRFs) were found in this region, and reporter assays identified a poly I:C-responsive promoter region (−506 to −398) that regulated LGP2 transcription. Transcriptional activity of the LGP2 promoter was strongly enhanced by IRF3, which bound to IRF3 motif #3 (−480). The LGP2 promoter was also responsive to viral infection in vitro. These results suggest that LGP2 transcriptional control is crucially involved to regulated by IRF3 function after viral infection or stimulation with poly I:C.
Highlights
Innate immunity is responsible for the immediate, acute immune response to pathogens
The relative increases in LGP2 mRNA were much greater than those of MDA5, which was induced by 1.8- and 11.89-fold at 24 and 48 hours, respectively, the total amount of each mRNA was similar at 48 hours
These results suggest that the transcriptional control of the LGP2 gene is different from that of the MDA5 gene, understanding the modulation of the expression of LGP2 and MDA5 genes could be interesting
Summary
Innate immunity is responsible for the immediate, acute immune response to pathogens. The CARDs of RIG-I and MDA5 interact with the CARD of IPS-1 (IFN-b promoter stimulator-1, known as MAVS, VISA or Cardif) as an adaptor molecule and initiates downstream signaling through activation of TBK1 (TANK-binding kinase1) and IKK-i (inducible IkB kinase) [8]. These kinases phosphorylate interferon regulatory factor (IRF)-3 and 27, which in turn activate transcription of type I IFNs and IFN-inducible genes (ISGs) [12]
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