FIS funds Harschnitz’s research on Herpes Simplex Virus latency
Oliver Harschnitz has been awarded a FIS Starting Grant for his proposal “Dissecting HSV-1 Latency and Reactivation using Trigeminal Organoids,” receiving funding of 1.3 million euros. The project, starting in March 2025, will run for three years.
Studying herpes simplex virus-1 (HSV-1) latency (a dormant state in the viral life cycle) in human trigeminal neurons is fundamental, as latency is a human-specific phenomenon. While 2D human stem cell models have provided important insights into antiviral immune mechanisms, their limited scalability and lack of complexity have made it challenging to study the molecular mechanisms underlying HSV-1 latency. Recent progress in directed differentiation methods and organoid technology allows for the development of three-dimensional (3D) organoids closely recapitulating specific brain regions. However, an organoid model of the trigeminal ganglion, which is part of the peripheral nervous system, is lacking.
In 3D HSV, the Harschnitz Group aims to develop a highly defined in vitro organoid model of the trigeminal ganglion building on the work of Eleonora Conti (PhD student) and other Harschnitz group members. The group will combine 3D organoids with cutting-edge genomics methods and CRISPR screens to dissect the host mechanisms that regulate HSV-1 latency in a human context, a prerequisite to develop therapeutic strategies to eradicate HSV-1 latency and prevent HSV-1 encephalitis. This innovative approach could pave the way for breakthroughs in treating HSV-1 and its severe complications.
Oliver Harschnitz explains: “HSV-1 encephalitis is the most common viral encephalitis in Western countries. It is a devastating brain disease and current antiviral treatment has limited efficacy, with survivors often suffering from severe neurological deficits. HSV-1 infects up to 90% of the global population and establishes latency in the trigeminal ganglion. The lack of therapeutic strategies to eradicate HSV-1 latency is in part due to the lack of knowledge of the HSV-1 life cycle and because of the absence of robust human experimental models in which to study HSV-1 latency. With our work, we hope to contribute to a better understanding of the life cycle of HSV-1 and the identification of potential therapeutic targets for future development.”
The FIS (Fondo Italiano per la Scienza), promoted by the Italian Ministry of University and Research, allocates €475 million to high-quality scientific research projects, aiming to promote the development of fundamental research in Italy. It adopts methods established at the European level, modelled after the European Research Council (ERC).
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