Antibodies to female Aedes albopictus salivary proteins promote dengue virus infection with salivary proteins

<h2>Abstract</h2><h3>Objective</h3> Mosquito saliva can facilitate arboviral infection, yet whether host antibodies to salivary proteins modulate dengue virus (DENV) infection remains unclear.To test whether antibodies induced by <i>Aedes albopictus</i> salivary proteins (AaSP) enhance DENV infection when AaSP is present. <h3>Methods</h3> We used RAW264.7 cells and <i>BALB/c</i> mice; generated anti-AaSP antisera; co-incubated DENV with AaSP; quantified NS1 mRNA, envelope protein, and cytopathic effects (CPE); and assessed tissue pathology. We compared female- versus male-derived AaSP and antisera, performed proteomics, tested recombinant Obp1 and D7L, purified IgG, and evaluated papain digestion and Fcγ receptor (anti-CD16/32, clone 2.4G2) blockade. <h3>Results</h3> Antiserum with AaSP increased DENV infection in vitro and aggravated pathology in vivo. Repeated <i>A. albopictus</i> bites induced anti-AaSP antibodies and led to more severe disease after infection with AaSP-preincubated virus. Only female-AaSP antisera enhanced infection; proteomics showed sex-distinct salivary profiles. Obp1 and D7L enhanced infection with antiserum. Purified IgG reproduced the increase, which was lost after papain digestion or FcγR blockade. <h3>Conclusion</h3> Anti-AaSP IgG can increase DENV infection in the presence of AaSP. These findings add to understanding of DENV pathogenesis and may help inform future exploration of prevention targets.