Part:BBa_K3646000
NS5 is a multidomain protein that encodes many functions. The NS5 N-terminus encodes a methyl transferase that induces methylation of guanine N7 and 2-hydroxyl ribose of the viral RNA cap. These modifications are required for viral replication. NS5’s most studied role is that of the viral RNA-dependent RNA polymerase (RdRp), which is encoded by its C-terminal domain. Over the past decade, flavivirus NS5 proteins have surfaced as potent antagonists of IFN signalling.
More relevant to our project FRaPPe, DENV NS5 targets STAT2 for proteasome-mediated degradation when expressed as a proteolytically processed precursor. Amino acids at the N terminus of DENV NS5 are required for STAT2 degradation but not for STAT2 binding. Essentially, NS5 binds signal transducer and activator of transcription 2 (STAT2) and inhibits its phosphorylation. However, NS5 alone does not induce degradation of STAT2, which occurs only when all non-structural proteins are expressed together (Mazzon et al., 2009).
The loss of STAT2 expression is conserved across the DENV serotypes and it occurs independent of the structural proteins.
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