Role of scavenger endothelial cells in elimination of virus
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. We will expose LSECs to several types of viruses and determine what receptors are involved in the uptake and 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. By this we aim 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. Moreover, the project will provide knowledge to control unwanted liver uptake of virus used as drug delivery vehicles.
Partners/collaborators:
Norwegian Research Council (NRC/NFR -FriPro)