Bacterial Extracellular Vesicles (BEVs) Derived from Chryseobacterium Inhibit Dengue Virus Infection by Disrupting Its Structural Integrity

ABSTRACT

Dengue virus (DENV) infection poses a significant global health threat, and current prevention and treatment strategies are limited by challenges of lacking effective mosquito control measures and antibody‐dependent enhancement. This study reports that bacterial extracellular vesicles (BEVs) secreted by a soil bacterium  Chryseobacterium aquifrigidense M24 exhibit potent anti‐DENV activity by triggering the structural disintegration of DENV particles prior to cellular entry in a dose‐dependent manner. Mechanistic investigations revealed that BEVs interact with the viral envelope, inducing premature membrane fusion. This process is characterized by reduced membrane fluidity and irreversible lipid rearrangement, leading to a significant increase in particle density, as shown by iodixanol gradient ultracentrifugation. The proposed ‘fusion‐triggered structural disruption’ is further supported by the induction of aberrant E protein oligomerization and morphological changes observed via transmission electron microscopy. This mechanism is specific to enveloped viruses, as BEVs showed no effect on non‐enveloped Enterovirus 71. Crucially, this BEV‐mediated inactivation extends to other enveloped viruses, including HCV, WNV and YFV, indicating broad‐spectrum potential. Our findings reveal a previously unexplored function of BEVs as virucidal agents, proposing a new ‘virus‐destructor’ strategy that contrasts with conventional fusion inhibitors and offering promising avenues for developing broad‐spectrum antiviral drugs.