<i>Aedes aegypti</i> salivary protein LTRIN activates pro-inflammatory genes in human dermal fibroblasts to counter mosquito-borne viral challenges

Mosquito salivary protein has attracted significant attention for its ability to either enhance or suppress the infectivity and pathogenicity of mosquito-borne viruses. LTRIN is an <i>Aedes aegypti</i> salivary protein with a 15 kDa fragment (named ΔLTRIN) detectable in mosquito saliva. Here, we report the effects of ΔLTRIN on the transcriptome profiles of human dermal fibroblasts at 3, 24, and 72 hours after exposure. At all three time points we observed an increase in pro-inflammatory genes such as <i>CXCL1</i>, <i>CXCL2</i>, <i>CXCL8</i>, and <i>ICAM1</i> which may be associated with the activation of interferon and IL6/JAK/STAT3 pathways. Co-infection of ΔLTRIN with ZIKV, DENV, or CHIKV during infections resulted in reduced virus titers, indicating that the presence of ΔLTRIN hinders transmission of mosquito-borne viruses by triggering upregulation of pro-inflammatory genes including interferons, cytokines and chemokines. The findings underscore the ability of ΔLTRIN to modulate immune responses, providing valuable insights into the molecular mechanisms by which ΔLTRIN enhances antiviral defense of human dermal fibroblasts.