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- W4313374733 abstract "Abstract Liver has many biological functions, including (but by no means limited to) the removal, from the blood, of various pathogenic organisms. This phenomenon has been best-studied for bacteria, and is thought to be mainly mediated by Kupffer cells and sinusoidal endothelial cells; these cells, too, have been implicated in clearance of some viruses. However, to date, hepatocytes - which constitute ~90% of the liver’s biomass - have been thought to be bystanders in this activity. Herein we show that hepatocytes directly protect the host against type B coxsackieviruses (CVBs) by engulfing, then rapidly silencing, these pathogens. Novel CARHEP KO mice, which carry a hepatocyte-specific deletion of the coxsackievirus-adenovirus receptor (CAR), are unable to capture circulating CVB3, leading to a dramatic early rise in blood-borne virus, followed by markedly-elevated morbidity, mortality, and increased viral load. The enhanced pathogenicity in CARHEP KO mice occurs despite the production of abundant type I interferon (T1IFN), which is derived from plasmacytoid dendritic cells (pDCs). In addition, we show that in genetically-intact (wild type; WT) mice, the rapid hepatocyte silencing of trapped virus is dependent on IRF1; in its absence, CVB3 undergoes efficient productive replication in hepatocytes and, as a result, virus titers in all tested extrahepatic tissues are several logs higher than in WT animals. In summary, hepatocytes act as a trap for CVBs, internalizing the viruses and reducing systemic viral burden, and thereby protecting the host from systemic disease." @default.
- W4313374733 created "2023-01-06" @default.
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- W4313374733 date "2020-05-01" @default.
- W4313374733 modified "2023-09-27" @default.
- W4313374733 title "Hepatocytes engulf and rapidly silence coxsackievirus, protecting the host against systemic viral pathology" @default.
- W4313374733 doi "https://doi.org/10.4049/jimmunol.204.supp.248.3" @default.
- W4313374733 hasPublicationYear "2020" @default.
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