Research by University of Bern scientists suggests that the mpox virus can also infect the human brain and damage brain cells, findings they say are important from a public health perspective in view of escalating cases in numerous countries.
The university and the Institute of Virology and Immunology (IVI) wrote that around 3% of all people infected with the mpox virus (MPXV) between 1985 and 2021 developed neurological symptoms like seizures or encephalitis. Some cases were fatal, reports Swissinfo.ch.
Under-studied
However, said the scientists, the extent to which the virus affects the human central nervous system is still poorly understood.
In collaboration with Lausanne University Hospital (CHUV) and the Spiez Federal Laboratory, a team from the University of Bern and the IVI therefore investigated whether the virus can spread in the human brain.
To do this, they used so-called brain organoids, three-dimensional mini-brains grown in the laboratory from human stem cells. These were exposed to a virus sample that had been isolated from a patient during the 2022 mpox outbreak.
The scientists then observed how the virus spread from cell to cell. This led to the formation of so-called neuritic beads, bead-like thickenings that are also known from neurodegenerative diseases like Alzheimer’s. The formation of these thickenings precedes the death of the nerve cells.
The research team also tested the effect of the antiviral drug Tecovirimat, which was able to significantly reduce the viral load in the brain organoids.
The results were published in Nature Communications.
Study details
Monkeypox virus spreads from cell-to-cell and leads to neuronal death in human neural organoids
Isabel Schultz-Pernice, Amal Fahmi, Francisco Brito et al.
Published in Nature Communications on 30 June 2025
Abstract
In 2022-23, the world witnessed the largest recorded outbreak of monkeypox virus (MPXV). Neurological manifestations were reported alongside the detection of MPXV DNA and MPXV-specific antibodies in the cerebrospinal fluid of patients. Here, we analyse the susceptibility of neural tissue to MPXV using human neural organoids (hNOs) exposed to a clade IIb isolate. We report susceptibility of several cell types to the virus, including neural progenitor cells and neurons. The virus efficiently replicates in hNOs, as indicated by the exponential increase of infectious viral titers and establishment of viral factories. Our findings reveal focal enrichment of viral antigen alongside accumulation of cell-associated infectious virus, suggesting viral cell-to-cell spread. Using an mNeonGreen-expressing recombinant MPXV, we confirm cell-associated virus transmission. We furthermore show the formation of beads in infected neurites, a phenomenon associated with neurodegenerative disorders. Bead appearance precedes neurite-initiated cell death, as confirmed through live-cell imaging. Accordingly, hNO-transcriptome analysis reveals alterations in cellular homeostasis and upregulation of neurodegeneration-associated transcripts, despite scarcity of inflammatory and antiviral responses. Notably, tecovirimat treatment of MPXV-infected hNOs significantly reduces infectious virus loads. Our findings suggest that viral disruption of neuritic transport drives neuronal degeneration, potentially contributing to MPXV neuropathology and revealing targets for therapeutic intervention.
Swissinfo.ch article – Mpox virus can also infect the brain, say Swiss scientists (Open access)
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