Spekare: Benjamin Nilsson-Payant, Karolinska Institute, Sweden
Host: Max Renner, Department of Chemistry, UCMR
Hantaviruses are zoonotic segmented negative-sense RNA viruses that asymptomatically circulate in rodents, shrews and bats. While most hantaviruses do not infect or cause disease in humans, some can cause highly pathogenic respiratory and renal disease characterized by a so-called ‘cytokine storm’ resulting in high mortality rates. The mechanisms underlying why some hantaviruses remain asymptomatic while others can cause severe disease are still unknown. Recently, the accumulation of defective viral genomes has been implicated in viral pathogenesis for other RNA viruses, including influenza A virus and respiratory syncytial virus.
In our lab, we are taking a systematic and comprehensive approach to compare and contrast the host response to a wide range of pathogenic and non-pathogenic Old World and New World hantaviruses in human and natural host species backgrounds using multi-OMICS methodologies. We can link the transcriptional host response to the full viral replication landscape of hantaviruses using a combination of short-read and long-read RNA sequencing methods and have identified several distinct defective viral genome populations that are correlated with the antiviral response. In order to understand the molecular details of viral replication and DVG production in the context of the host cell, we are investigating the replication environment and identifying protein interaction partners of the hantavirus polymerase. Our aim is to identify critical host factors for viral replication and host adaptation that can serve as potential antiviral drug targets.
Our data helps to shed new light on the intricate processes that govern virus-host interactions during hantavirus replication and might help explain the underlying mechanisms of disease. These insights will aid our quest to further understand viral pathogenesis and to develop novel treatment strategies.