Our preliminary work shows that aberrant viral replication and the generation of defective viral genomes (DVGs) are a universal feature of negative-sense RNA viruses and that these DVGs are potent stimulants of the host interferon response. Thus, we would like analyze the mechanisms regulating DVG synthesis and the consequences thereof for viral pathogenesis of emerging RNA viruses.
Here, we are taking a multi-omics approach complemented with viral engineering and molecular biology tools to characterize the entire viral transcriptome/replicome and to identify the association between specific viral PAMPs and immune activation in vitro and in vivo.
About the illustration: On the left, it can be seen that the RNA of the hantavirus (viral genome RNA) is sensed by cellular RNA sensors that trigger an interferon (IFN) response culminates in activation of antiviral genes. Viral IFN antagonists are able to inhibit IFN signalling. On the right, aberrant replication products / defective viral genomes accumulate to high numbers during viral replication. They are able to overwhelm the host’s innate immune system, leading to a prolonged and excessive IFN response. Thus, highly inflammatory and pathological infections can occur.