Defective hantavirus genomes as a determinant of the host immune response and pathogenesis

Hantaviruses are a family of zoonotic viruses naturally found in rodents. In humans some hantaviruses can cause highly pathogenic disease.

Hantavirus-induced disease is characterised by inflammation, vascular leakage and acute renal and respiratory failure, with mortality rates of up to 40%. Neither effective antiviral treatment options nor vaccines against any hantavirus have been licensed yet.

Due to the high prevalence of their reservoir species and their potential lethality, it is of critical importance to gain a better understanding of the molecular mechanisms underlying hantavirus pathogenicity.

The error-prone RNA polymerase (RdRp) of all RNA viruses is known to generate aberrant replication products, missing essential regions of viral genomes.

These so-called defective viral genomes (DVGs) have been described for many RNA virus families and have been shown to strongly activate the host innate immune system by inducing interferon signalling.

In fact, for some viruses, including influenza A virus, the accumulation of DVGs strongly correlates with increased disease severity.

This project aims to characterise the defective viral transcriptome of hantaviruses and how (defective) viral RNA induces the innate immune response.

The answers to these questions and the tools developed in this project will help us determine the fundamental molecular mechanisms that underlie innate immune sensing, interferon induction and pathogenesis in hantavirus infections.