FIGURE 1.

Flavivirus entry and uncoating is followed by virus RNA sensing by: (i) TLR3 and 7 present in endosomal vesicles; (ii) RIG-I or MDA5 at the cytoplasm; (iii) NOD-like receptors (NLR) at the cytoplasm. (i) ssRNA or dsRNA are sensed by TLR7 or TR3, respectively. TLR activation leads to activation of IRFs, NF-κB, and MAPK and their translocation to the nucleus, inducing the production of interferons, proinflammatory cytokines and cell death. (ii) dsRNA sensing by RIG-I induces a conformational change of CTD, allowing exposition of CARD. CARD domain is then targeted by the ubiquitin ligases, which promotes its polyubiquitination and MAVS recruitment. RIG-I/MAVS activation promotes activation of IRFs, NF-κB, and MAPK and their translocation to the nucleus, inducing the production of interferons, proinflammatory cytokines and cell death. (iii) RNA sensing together with other stress signals (ROS, increased Ca²⁺ and/or H⁺) activates inflammasome complexes, inducing caspases 1/11 activation and IL-1β and IL-18 secretion.