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bioRxiv · 10.64898/2026.08.23.746568

Myeloperoxidase (MPO) exacerbates dengue-associated liver injury and contributes to disease pathogenesis in mouse models

Victorio, C. B. L.·Teo, A.·Gupta, S.·Ganasarajah, A.·Ong, J. L.·SK, J.·Rabelo, K.·Alves, L. L.·Basilio-de-Oliveira, C. A.·Basilio-de-Oliveira, R. P.·Chia, P. Y.·Kuruppu, H.·Karunananda, M.·Idampitiya, D.·Wijewickrama, A.·Jeewandara, C.·Malavige, G. N.·Yeo, T. W.·Chacko, A.-M.
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Abstract

Severe dengue can damage the liver through unestablished mechanisms. We investigated the role of myeloperoxidase (MPO), a neutrophil enzyme, in dengue through patients, fatal liver samples, and mouse infection models. Observations from two independent clinical cohorts revealed elevated plasma MPO levels in dengue and, in one cohort, MPO was further linked to liver injury markers during the critical phase of disease, whereas livers from dengue fatal cases revealed MPO build-up in the vicinity of CD177+ activated neutrophils. In mice, dengue led to MPO overexpression, oxidative damage, and broad activation of innate and systemic inflammatory pathways in livers. Blocking MPO activity alleviated these and improved survival in one model and delayed disease progression without preventing death in another. These findings establish MPO as a functional mediator of severe dengue-associated liver injury and inflammation, which warrants further preclinical investigation into its hepatic pathogenic mechanism and its validity as target for therapeutic intervention.

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Victorio, C. B. L., Teo, A., Gupta, S., Ganasarajah, A., Ong, J. L., SK, J., Rabelo, K., Alves, L. L., Basilio-de-Oliveira, C. A., Basilio-de-Oliveira, R. P., Chia, P. Y., Kuruppu, H., Karunananda, M., Idampitiya, D., Wijewickrama, A., Jeewandara, C., Malavige, G. N., Yeo, T. W., Chacko, A.-M.. 2026-08-27. Myeloperoxidase (MPO) exacerbates dengue-associated liver injury and contributes to disease pathogenesis in mouse models. https://doi.org/10.64898/2026.08.23.746568

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