Giardiavirus infection alleviates growth restriction and intestinal damage caused by the intestinal parasite Giardia duodenalis.

BACKGROUND

Giardia duodenalis is a prevalent intestinal pathogen causing giardiasis, a condition characterized by diarrhea and frequently linked to malnutrition and growth impairments in children. The virulence of Giardiavirus (GLV) may efficiently clear Giardia parasites from infected patients. However, we have a limited understanding of GLV transmission among Giardia species and GLV-infected Giardia's impact on pathogenicity.

METHODS

This study investigated extracellular vesicles (EVs) isolated via ultracentrifugation or exosome assay kit to detect the presence of GLV in EVs, the results were detected using ultrastructure and molecular methods, including transmission electron microscopy, scanning electron microscopy, quantitative polymerase chain reaction (qPCR), and dot blot. Transwell migration assays confirmed the spread of GLV-enveloped EVs among Giardia species using inhibitor experiments and immunofluorescence. Mice gavaged with Giardia, with or without GLV infection, were assessed for disease progression, including growth parameters (weight and size gains), intestinal permeability, and pathology.

RESULTS

Parts of GLV exploit the Giardia EVs pathway to reach the extracellular environment, allowing GLV to spread among Giardia species via these EVs. The uptake of GLV-containing EVs by Giardia results in rapid trophozoite infection, and GLV wrapped in EVs also offers protection against external interference. Importantly, EV-coated GLV-infected Giardia leads to divergent clinical symptoms in mice, posing less risk to mice and reducing symptoms, such as emaciation, stunted growth, and lesion damage, compared with GLV-free Giardia-infected mice.

CONCLUSIONS

Our studies show that GLV wrapped in EVs can spread among Giardia species, and GLV infection alleviates the lesions caused by Giardia. These findings reveal that GLV could be a target for the development of novel intervention strategies against Giardia.