Herein, we show that LGP2 is strongly upregulated by dsRNA stimulation or virus infection in cultured human cell lines via TLR3 and RLRs, respectively, and that substantial induction of LGP2 remains when paracrine/autocrine signalling of IFNs and/or inflammatory cytokines is abrogated by genetic deletion or chemical inhibition. Here, DHX58 is linked to viral infectious disease.