Yellow Fever Virus Interactomes Reveal Common and Divergent Strategies of Replication and Evolution for Mosquito-borne Flaviviruses.

ABSTRACT: Pathogenic mosquito-borne flaviviruses infect mosquito and human hosts, relying on host protein interactions to replicate, evade immunity, and mediate pathogenesis. Prior proteomic studies mapped such interactions for some flaviviruses, but yellow fever virus (YFV)-a pathogen of resurgent concern-remains understudied. Here, we map YFV interactomes in human and mosquito cells to identify interactions common among divergent flaviviruses or unique to YFV. Functional assays reveal a previously unrecognized YFV restriction factor: RBBP6 inhibits YFV genome replication by interacting with the viral polymerase NS5. We enhance the identification of dual-host interactions using structural modeling and holistic network integration. Extending our holistic approach to other flavivirus interactomes, we

SUBMITTER: Kenaston MW 

PROVIDER: S-EPMC12236827 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature