Dengue Virus Evasion of Host Innate Immunity

Infection with dengue virus (DENV) is a major global public health threat, driven by mosquito transmission of four closely related virus serotypes. For effective transmission between hosts, DENV rapidly remodels the host cell to overcome multiple innate immune barriers and produce progeny virions. Here we review how DENV evades cell-intrinsic sensing and interferon (IFN) responses in both human and mosquito hosts. We highlight the roles of replication organelles, nonstructural proteins NS2B/3 and NS5, and subgenomic flaviviral RNAs in escaping RIG-I-like receptor and cGAS-STING signaling, disrupting JAK-STAT pathways, and subverting autophagy and ER-phagy. We further discuss NS1-mediated vascular leak, exploitation of TAM receptors, serotype-specific differences in IFN antagonism, and how these mechanisms might shape pathogenesis, host range, and epidemiological fitness. Finally, we consider how defined immune evasion strategies inform rational design of antivirals and next-generation live-attenuated tetravalent dengue vaccines to mitigate the escalating global dengue burden.