Project

In the moonlight of GTF3A: a new way to see innate antiviral signaling?

Duration
01 November 2020 → Ongoing
Funding
Research Foundation - Flanders (FWO)
Research disciplines
  • Medical and health sciences
    • Applied immunology
    • Inflammation
    • Hematology
    • Immunogenetics
    • Innate immunity
Keywords
Herpes encephalitis Herpes viral infections Innate viral sensing
 
Project description

Herpes viruses are omnipresent in the human population and cause a range of benign but unpleasant diseases. However, in a small percentage of people, infections with herpes viruses become recurrent or invasive resulting in increased morbidity and mortality. The quintessential example is herpes encephalitis (HSE) that causes neurological sequela in most patients and lethality up to 25% even with appropriate antiviral treatment. The immune system recognizes herpes viruses through a wide variety of receptors. Monogenic inborn errors of these signaling cascades underpin the susceptibility for herpes virus infection in patients with HSE. In this study, we propose further functional validation of compound heterozygous GTF3A missense variants found in a patient with HSE. Given the strong association of invasive herpes virus infections with monogenic inborn errors of immunity and our convincing preliminary data pointing towards the causal role of compound heterozygous GTF3A mutations in the clinical phenotype, we postulate that GTF3A acts as a novel player in immunity against herpesviruses. With the herein proposed research, we aim to substantially contribute to basic knowledge on GTF3A and its relevance in immunological processes. In turn, we believe that this research will enhance our understanding of viral immunity and improve the diagnostic evaluation and therapeutic approaches of patients with invasive herpes infections.