Participation of dengue virus NS4B protein in the modulation of immune effectors dependent on ER stress in insect cells.

Organisms' reactions to adverse events result in the generation of immune effectors, which, in the case of insects, may be produced from the direct activation of pathways such as Toll, Jak-STAT, Imd, or RNAi or may be derived from the crosstalk of different intracellular pathways. One such pathway, the unfolded protein response (UPR), has the primary objective of restoring homeostasis in the endoplasmic reticulum. In addition, the UPR participates in signaling crosstalk with the immune pathways, generating protection against pathogenic organisms. Dengue virus is a plus-strand RNA virus belonging to the Flavivirus genus that uses the ER as a replication site; during the infection, there are indicators of the activation of the UPR, which in turn, induces the synthesis of internal membranes and preferential translation of viral proteins enhancing the replication. One of the dengue virus proteins, the NS4B can block the pathway of α/β interferon in mammals. However, what happen in insects is interesting because the lack of the main antiviral pathway, the interferon and the role of the NS4B protein in the UPR-immunity relationship can be better understood. Thus, in this study, we demonstrated that the DENV2/16681 NS4B protein is capable of modulating the immune effectors that result from the activation of the UPR in insect cells.