Published on 18 May 2026

Blog Isabel Schultz-Pernice – Organoids

“We anticipate that our findings will contribute to a deeper understanding of the pathologies associated with monkeypox virus, tick-borne encephalitis virus, and Zika virus […]”

Brain Teasers – exploring neurotropic virus infection using organoids

Due to human related factors, public health emergencies caused by zoonotic pathogens have increased markedly over the recent decades. Among these pathogens, neurotropic viruses represent a particularly serious threat to human health. Despite their global significance, important aspects of the viral life cycle and the host-pathogen interactions that shape disease outcomes and therapeutic susceptibility remain incompletely understood.

To address these knowledge gaps and contribute to improved outbreak preparedness, my thesis investigated key aspects of viral pathogenesis in monkeypox virus, tick-borne encephalitis virus, and Zika virus using human neural organoids - an advanced in vitro model of the human brain. Our findings demonstrate that complex in vitro systems can provide valuable insight into host-pathogen interactions across multiple scales, ranging from fundamental mechanisms of infection to the identification of potential therapeutic strategies.

Interview with Dr Isabel Schultz-Pernice

• What was the aim of your thesis?

  During my thesis, I aimed to elucidate key aspects of the neuropathogenesis associated with three viruses: monkeypox virus, tick-borne encephalitis virus, and Zika virus. I investigated these pathogens across multiple levels, ranging from fundamental mechanisms of infection to the evaluation of potentially clinically relevant antiviral strategies. To achieve this, I employed human neural organoids, a three-dimensional in vitro model that recapitulates key features of the human brain.

• What are the main findings of your thesis?

  In my first project, we investigated the mechanisms underlying mpox encephalitis, a rare but severe neurological complication. We found that the monkeypox virus spreads directly between neurons through axons and dendrites. Based on our observations, we hypothesize that the virus hijacks the host cell’s intracellular transport machinery, thereby disrupting normal cellular functions. Consistent with this, infected neurons developed sequential swellings along neurites - indicative of neuronal damage - and ultimately underwent cell death. In line with these findings, we demonstrated that the antiviral drug Tecovirimat reduces viral spread but does not fully prevent neuronal injury.

  In my second project, I focused on tick-borne encephalitis virus, an endemic pathogen with steadily increasing incidence. We found that infection in human neural organoids recapitulates key features of tick-borne encephalitis, including pronounced neuronal death. In collaboration with the Institute for Infectious Diseases (IFIK) in Bern and the Veterinary Research Institute in Brno (Czechia), we subsequently evaluated the efficacy of four antiviral compounds against tick-borne encephalitis virus infection. By integrating multiple in vitro and ex vivo models, we identified two compounds that effectively inhibit viral replication across physiologically relevant systems.

  In my third project, we collaborated with the Centre Hospitalier Universitaire Vaudois (CHUV) to investigate the mechanisms of Zika virus cell entry. We found that the protein plasminogen activator inhibitor-1 contributes to early steps of Zika virus infection – a finding with potential therapeutical implications.

  

  Immunofluorescence image of a sectioned human neural organoid showing its inner organization and major cell populations. Neural progenitor cells (magenta) form hollow ventricle-like structures, which are surrounded by dense layers of neurons (yellow). Cell nuclei are shown in blue. Scale bar, 1 mm.

• To what extent will your findings help to advance research?

  Despite substantial research efforts, many diseases caused by neurotropic viruses remain incompletely understood, and therapeutic options are often limited to supportive care. We anticipate that our findings will contribute to a deeper understanding of the pathologies associated with monkeypox virus, tick-borne encephalitis virus, and Zika virus, thereby helping to pave the way for the development of more effective therapeutic strategies for affected patients.

• What aspect of this work are you especially proud of?

  Since my master’s studies, I have been particularly interested in the use of complex human in vitro models and their potential to drive scientific research while adhering to the 3R principles -replacement, reduction, and refinement of animal use in research. Through my work, I have contributed to the understanding of diverse viral pathologies using a range of in vitro systems, highlighting the value and potential of these models in advancing biomedical knowledge. This is an aspect of my work of which I am especially proud.

• What did you especially like about your thesis?

  I greatly enjoyed acquiring advanced laboratory skills and now deeply value the opportunity to share this knowledge through teaching and mentoring other students. From human neural organoid culture to work with biosafety level 3 pathogens, these four years have been a continuous process of learning, growth, and refinement of my technical expertise – an experience I have found highly rewarding.

  I also greatly appreciated the opportunity to contribute to such a contemporary and rapidly evolving field of research using state-of-the-art methodologies. In a world where zoonotic virus outbreaks are becoming increasingly relevant, advancing our understanding through complex human model systems represented an ideal combination of two highly important and intellectually stimulating areas of research.

• How was your time at the IVI?

  I had a wonderful time at the IVI and deeply valued every aspect of the experience. The supportive working environment and the exceptional team I had the privilege to join fundamentally contributed to every stage of my PhD journey. During this time, I came to truly appreciate that teamwork is an essential component of successful research and that the support of inspiring and trusted colleagues is invaluable.

  I am deeply grateful for the remarkable group of people I was fortunate enough to call my colleagues throughout these years.

• What are your plans now, what are you going to do next?

  During my dissertation, I had the privilege of learning from many outstanding researchers who served as true mentors to me. This fundamental personal experience is something I hope to pass on to other early-career researchers within our team.

  In the coming months, I will continue my teaching and research activities in the “Cell & Infection Biology Lab” of Prof. Dr. Marco Alves, advancing ongoing projects, exploring novel research directions, and supporting newer lab members as they develop their skills. I am also excited to continue and complete the Certificate of Advanced Studies (CAS) in “One Health” at the University of Bern, in which I am currently enrolled.

Publications

• Monkeypox virus spreads from cell-to-cell and leads to neuronal death in human neural organoids | Nature Communications
• Bemnifosbuvir and remdesivir inhibit tick-borne encephalitis virus infection in complementary in vitro and ex vivo disease models | bioRxiv
• Plasminogen activator inhibitor-1 regulates Zika virus infection | Research Square