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Human liver-derived organoids recapitulate Oropouche virus infection and manifestation, enabling antiviral drug discovery

ABSTRACT: Oropouche virus (OROV) is a neglected, re-emerging arbovirus that typically causes self-limiting febrile illness but can also result in severe complications. Currently, there are no approved vaccines or treatments for OROV infection. We integrated clinical data from OROV-infected patients with human liver-derived organoid models to investigate the virus's impact on the liver and evaluate repurposed antivirals. Patient blood tests show elevated liver enzymes, suggesting OROV-associated hepatic dysfunction. OROV isolates productively infect liver organoids and induce severe cellular damage. Transcriptomic profiling reveals strong virus-host interactions, including activation of interferon-stimulated genes and cell death pathways. Pharmacological inhibition of the interferon pathway enhances OROV replication, whereas treatment with therapeutic interferon-α suppresses the infection. Molnupiravir, a clinically approved antiviral targeting viral RNA-dependent RNA polymerase, markedly inhibits OROV replication and mitigates virus-induced cytopathology. Combining molnupiravir with interferon-α resulted in synergistic antiviral activity, indicating the complementarity of virus-targeted and host-directed strategies.

ORGANISM(S): Homo sapiens

PROVIDER: GSE316780 | GEO | 2026/01/21

REPOSITORIES: GEO

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