Published on 30 June 2025

Can the Mpox (Monkeypox) virus spread in the human brain?

Monkeypox virus infection (green) triggers neuritic beads indicating neurodegeneration in brain organoids. Scale bar 25 um. — © Copyright IVI

Researchers from the Institute of Virology and Immunology (IVI) and the University of Bern, in collaboration with the Lausanne University Hospital (CHUV) and the Spiez Federal Laboratory, have discovered that the monkeypox virus (MPXV, mpox virus) can spread efficiently in brain organoids, leading to neuronal cell death. Their findings shed light on a previously unexplored aspect of MPXV infections. This research was supported by the Multidisciplinary Center of Infectious Diseases (MCID) at the University of Bern.

• Why is this study important ?

  Mpox, the disease caused by the monkeypox virus (MPXV), has been poorly investigated in the past, mainly due to its geographical restriction. Serious complications caused by the MPXV have been particularly neglected. With our study we investigated a previously unexplored aspect of the mpox diseas, showing that the MPXV can infect the human brain potentially causing serious damage. Given the recent surge in mpox cases, our findings are relevant: they not only shed light on the virus pathology but also point to possible treatments, which is crucial for public health and safety.

• Description of the study

  Little is known about the impact of an  MPXV infection in the human brain. To explore this aspect of the mpox disesase, we exposed human brain organoids to a MPXV isolate from a 2022 Swiss patient. We monitored viral replication, and observed its effects on neural cells over time. Using live-cell imaging, we confirmed cell-to-cell viral spread along neuronal filaments. We also tested antiviral treatments to assess their effectiveness in reducing the infection.
  
  Brain organoids are 3D tissue models generated from human pluripotent stem cells. As they mature into neural cells, they develop into structures that mimic specific features of the brain. Brain organoids are complex to cultivate. However, they hold enormous potential for researching neurological diseases using a complex human-based model, while mitigating ethical concerns and practical limitations of animal experimentation, in line with the 3R principles.

• What are the main findings

  We found that the MPXV, efficiently infects human brain organoids and spreads directly from cell-to-cell, leads to neuronal death. This viral spread occurs without obvious damage to the outer morphology of the tissue, but causes the formation of serial swellings, termed “neuritic beads”, a hallmark of neurodegenerative diseases such as Alzheimer’s. Furthermore, we showed that MPXV infection can be significantly reduced applying the antiviral drug tecovirimat, suggesting potential therapeutic strategies.

  While MPXV has been known to cause skin lesions and systemic effects, we were surprised by how it spreads in the brain. The lack of major changes in the outer morphology of the brain organoids, despite significant neuronal damage, was unexpected. The discovery that neuritic bead formation precedes neuronal cell death adds a new layer to our understanding of the virus’s pathological potential.

• Next step

  In future, we aim to dig deeper into our findings, to further elucidate the mechanisms behind our observations. Furthermore, we are currently observing an increase in the number of mpox cases caused by other MPXV lineages, so called “clades”. We are eager to determine whether our findings are specific to the virus isolate used in our study, or if the same mechanism can be observed with other MPXV clades as well. Also, we are constantly working on increasing the complexity of our organoid model, to mirror the human brain even better. The integration of microglia, an immune cell type specific to the brain, is one of the improvements we are currently working on. The use of similar organoids with increased complexity, could help us in gather more information on how our immune system reacts to a MPXV infection in the brain.

Title and link publication (Nature Communications 30.6.2025)
Monkeypox virus spreads from cell-to-cell and leads to neuronal death in human neural organoids | Nature Communications

Authors
Isabel Schultz-Pernice, Amal Fahmi, Francisco Brito, Matthias Liniger, Yen-Chi Chiu, Teodora David, Blandina I. Oliveira Esteves, Antoinette Golomingi, Beatrice Zumkehr, Markus Gerber, Damian Jandrasits, Roland Züst, Selina Steiner, Carlos Wotzkow, Fabian Blank, Olivier B. Engler, Artur Summerfield, Nicolas Ruggli, David Baud and Marco P. Alves

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