SECVIR - Role of scavenger endothelial cells in elimination of virus

Blood borne virus is rapidly eliminated by the liver via mechanisms that are not well understood. Most reports on hepatic uptake of virus have focused on Kupffer cells. Based on the recently emerging awareness that the liver sinusoidal endothelial cells (LSECs) are pivotal as scavengers of circulating large molecules and nano material, we put forward the hypothesis that the LSEC is a central player in the cellular arm of the anti-viral innate immune system. This will be studied by bringing together front-line interdisciplinary expertise in virology, optical nanoscopy, cell and molecular biology, and hepatology with the aim to study interaction of virus with LSECs to a level that has never before been attainable. We are one of very few laboratories that have access to fully functionally intact human LSECs. We will expose LSECs to several types of viruses and determine what receptors are involved in the uptake. We will use cutting edge live cell optical superresolution microscopy and correlative light and electron microscopy to follow the intracellular fate of viruses after entry into LSECs. We will study gene and protein expression in LSECs after uptake of virus, and establish if treatment of the cells with selected immunomodulators can strengthen the LSEC anti-viral defense. Our studies are expected to reveal mechanisms of how pathogenic viruses enter LSECs, and how the cells can be triggered to eliminate same viruses to avoid dissemination or latency. Our results will be important because there is an immediate need to find remedies to fight the increasing incidence of reactivation of e.g. dormant polyomavirus, and CMV associated with immunosuppressive therapy. The knowledge obtained will yield novel means of boosting hepatic metabolic elimination of normally pathogenic viruses. Moreover, the project will provide knowledge to control unwanted liver uptake of virus used as drug delivery vehicles.

Project period: 2017 - 2024

Funding: Norwegian Research Council (NRC)

Project leader: Karen Kristine Sørensen, Vascular biology research group

This project is a collaboration between UiT The Arctic University of Norway, University Hospital North Norway, University Hospital Basel/University of Basel, University of Alabama, Tokyo Institute of Technology, University of Bielefeld, Karolinska Institute and Uppsala University.

https://www.forskningsradet.no/prosjektbanken/#/project/NFR/262538