Orthohantaviruses are zoonotic RNA viruses found in insectivore and rodent hosts worldwide, establishing asymptomatic, persistent infections in their respective reservoir hosts. The vascular endothelium is the primary cellular target of orthohantavirus infection resulting in vascular leakage and thrombocytopenia in human disease. Research in the Kell lab is focused on defining the virus-host interactions in pathogenic Old World orthohantavirus infection, and their molecular mechanisms that program innate immunity and differential disease outcome among reservoir rodent hosts and humans.

Pathogen Recognition/Immune antagonism

The innate immune response is the first line of defense against viral infection. Our studies suggest that the cytosolic pathogen recognition receptors, RIG-I and MDA5, are required for early innate immune activation following Hantaan virus (HTNV) infection of human endothelial cell cultures, but not required for viral control or clearance in non-reservoir rodents in vivo. The lab has active projects to investigate the signaling pathways in human target endothelial cells that are activated in response to HTNV infection and defining the mechanisms of innate immune antagonism by HTNV in vitro and in vivo.

Mechanisms underlying infection outcome

Using a comparative genomics approach, we performed RNA sequencing on reservoir rodent (rat) and non-reservoir (human) endothelial cells infected with the Seoul orthohantavirus (SEOV). Bioinformatics analysis suggested differential modulation of VEGF receptor signaling pathway and markers of endothelial activation when comparing reservoir and non-reservoir transcriptional responses following infection. The lab has funding to study host-specific differences in functional responses to SEOV infection in endothelial cells and to identify the virus-host interactions that drive these responses.