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

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.