Insect anionic septapeptides suppress DENV replication by activating antiviral cytokines and miRNAs in primary human monocytes.

Dengue viruses (DENVs) have threatened 2/3 of the world population for decades. Thus, combating DENV infection with either antiviral therapy or protective vaccination is an urgent goal. In the present study, we investigated the anti-DENV activity of insect cell-derived anionic septapeptides from C6/36 mosquito cell cultures persistently infected with DENV. These molecules were previously shown to protect C6/36 and Vero cells against DENV infection. We found that treatment with these septapeptides strongly and rapidly downregulated the multiplication of DENV-1 16007, DENV-3 16562, and DENV-4 1036 but not that of DENV-2 16681 in primary human monocytes. This inhibitory effect was likely mediated through various routes including the increased production of antiviral cytokines (IFN-I), activation of mononuclear cell migration, and upregulation of the expression of antiviral miRNAs (has-miR-30e*, has-miR-133a, and has-miR-223) and inflammation-related miRNAs (has-miR-146a and has-miR-147). In conclusion, anionic septapeptides exerted anti-DENV activity in human monocytes through the upregulation of innate immune responses and the activation of several previously reported antiviral and inflammation-related miRNAs.