Enteric virus infection was boosted by the accumulation of micro- and nano-particles in host cells

Micro- and nano-plastics (MNPs) are emerging environmental contaminants that can readily enter and accumulate in the human body, yet their effects on viral infections remain largely unknown. This study provides the first evidence that polystyrene-based MNPs (MNP-PS) promote viral dissemination through an extracellular vesicle (EV)-mediated mechanism. Using murine norovirus (MNV-1), a surrogate for human norovirus, and RAW 264.7 macrophages as a representative host model, we found that pre-exposure to MNP-PS significantly enhanced viral infection. Bare MNP-PS induced stronger effects than carboxyl- or amine-functionalized MNP-PS. Mechanistic analyses demonstrated that pre-exposure to MNP-PS stimulated the release of virus-encapsulating EVs (viral vesicles) through multiple cellular pathways. Hydrophobic bare MNP-PS primarily triggered physical disruption of the cell membrane, whereas amine-functionalized and micro-sized particles mainly induced intracellular oxidative stress. These stress responses promoted the secretion of viral vesicles that were more infectious than free viral particles. Simultaneously, pre-exposure MNP-PS downregulated the expression of innate immune cytokines (TNF-α, IL-6, and IFN-β) following viral infection, thereby impairing host antiviral defense. Together, the enhanced release of viral vesicles and the suppression of immune responses promoted more efficient viral propagation. Overall, this work identifies a previously unrecognized health risk of MNP exposure, provides mechanistic insight into how environmental particles modulate host-virus interactions, and underscores the need to consider microplastic contamination as a potential cofactor in viral transmission and disease progression.