Dengue Virus Utilizes NBR1 During Induced Lipophagy and for Viral Egress

Dengue virus (DENV) infection induces a proviral lipophagy to mobilize lipids from the lipid droplet. Τhis study demonstrates that the selective autophagy receptor Neighbor of BRCA 1 (NBR1) is recruited to lipid droplets after DENV infection. Silencing NBR1 does not alter the induction of autophagy in DENV-infected cells, but specifically inhibits the DENV NS4A & NS4B-induced depletion of lipid droplets. Silencing NBR1 does not impact RNA replication nor viral assembly but does inhibit release of infectious particles via a non-canonical secretion method. Exogenous addition of free fatty acids allows DENV to leave via this uncharacterized method in NBR1 silenced cells. This uncharacterized secretion method possibly allows DENV to escape the cell in an extracellular vesicle protecting it from antibody neutralization. The data from this study suggests that NBR1 and DENV induced lipophagy play a critical role in the autophagic secretion of DENV.