Project Details
Projekt
Comparative analysis of varicella zoster virus spread, immune control and evasion employing complex skin and neuronal organoids
Subject Area
Virology
Term
since 2025
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 443644894
Varicella zoster virus (VZV) is a highly prevalent human pathogen that causes mild diseases as well as others associated with high morbidity and mortality, such as chronic pain, encephalitis and meningitis. The latter occurs more frequently in individuals with inborn errors of immunity in genes involved in VZV restriction, such as RNA polymerase III (POLIII). The outcome of infection depends on the ability of VZV to spread through different cell types in the skin and ganglia of the peripheral nervous system (PNS), and the ability of the cells to restrict the virus. How VZV spreads in these organs and how the intrinsic and innate immune responses control VZV is not well understood, partly because VZV is human specific. We have successfully infected skin and PNS organoids with reporter VZV to follow its spread, as well as established tools to investigate the mechanism of action of known restriction factors including POLIII and promyelocytic leukemia nuclear bodies. In this project, we will expand this mechanistic characterization while discovering novel restriction factors. Specifically, we aim to (i) understand how VZV spreads in the skin and PNS; (ii) to characterise the mechanism of action of known and novel antiviral factors and (iii) to discover how VZV evades and modulates these restriction factors. To do so, we will apply classical virology and omics techniques to investigate infection in organoids. Overall, this project will provide a broad overview of VZV pathogenesis revealing key information on VZV spread and potential novel mechanisms of intervention.
DFG Programme
Research Units
Subproject of
FOR 5200:
Disrupt - Evade - Exploit: Gene expression and host response programming in DNA virus infection (DEEP-DV)
International Connection
Denmark
Cooperation Partner
Professorin Trine Mogensen
