Raj, S.; Ranjith-Kumar, C. T.; Irfan, M.

Chikungunya virus (CHIKV) is a single-stranded positive-sense RNA virus that employs various strategies to evade the host\'s immune response. The CHIKV non-structural protein 2 (nsP2) is one of the viral-encoded proteins essential for viral replication as well as modulation of the immune response. In this study, we demonstrate that CHIKV nsP2 suppresses both RIG-I-like receptors (RLR) and Toll-like receptors (TLR) signaling pathways. Domain mapping of the nsP2 identified the N-terminal region encompassing the N-terminal domain and the helicase domain (NH) is responsible for the inhibition. Furthermore, site-directed mutagenesis experiments showed that functional helicase is necessary for inhibiting interferon production, but the C-terminal V-Loop region, previously implicated in host transcriptional shutoff, is not. In addition, nsP2 disrupts two key immune signaling pathways: RLR and TLRs, by blocking common proteins such as TBK1 and IRF3.