Host serum-derived flavivirus NS1 co-opts mosquito miRNA processing to suppress early immune defense

ABSTRACT: Flaviviruses pose growing global health threats and are transmitted by Aedes mosquitoes. Yet, how these viruses overcome early mosquito immunity remains unclear. Here, we reveal a cross-host immune evasion strategy in which the flavivirus NS1 protein, abundantly secreted into infected human serum, is taken up by mosquitoes during blood feeding and rapidly internalized into midgut epithelial cells—prior to viral replication. NS1 hijacks the mosquito spliceosome-associated factor Prp19 to promote miR-275-5p maturation, which suppresses the caspase gene CASPS19, blocking apoptosis and enabling early viral replication. Engineered mosquitoes expressing a miR-275 sponge show enhanced resistance to dengue and Zika viruses. These findings uncover a previously unrecognized mechanism whereby a vertebrate-derived viral protein reprograms vector gene regulation, establishing a new paradigm of cross-species immune manipulation by flaviviruses.

INSTRUMENT(S):

ORGANISM(S): Aedes Aegypti

TISSUE(S): Midgut

SUBMITTER: yifei Li  

LAB HEAD: Sibao Wang

PROVIDER: PXD067301 | Pride | 2026-08-18

REPOSITORIES: Pride