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Published on: February 3, 2012
Hepatocytes trap and silence coxsackieviruses, protecting against systemic disease in mice
Taishi Kimura1, Claudia T Flynn2, J Lindsay Whitton3
1Department of Immunology and Microbiology, The Scripps Research Institute, 10550N. Torrey Pines Rd., La Jolla, CA, 92037, USA. tkimura@scripps.edu.
Abstract:
Previous research suggests that hepatocytes catabolize chemical toxins but do not remove microbial agents, which are filtered out by other liver cells (Kupffer cells and endothelial cells). Here we show that, contrary to current understanding, hepatocytes trap and rapidly silence type B coxsackieviruses (CVBs). In genetically wildtype mice, this activity causes hepatocyte damage, which is alleviated in mice carrying a hepatocyte-specific deletion of the coxsackievirus-adenovirus receptor. However, in these mutant mice, there is a dramatic early rise in blood-borne virus, followed by accelerated systemic disease and increased mortality. Thus, wild type hepatocytes act similarly to a sponge for CVBs, protecting against systemic illness at the expense of their own survival. We speculate that hepatocytes may play a similar role in other viral infections as well, thereby explaining why hepatocytes have evolved their remarkable regenerative capacity. Our data also suggest that, in addition to their many other functions, hepatocytes might be considered an integral part of the innate immune system.
Insights
Hepatocytes trap and silence coxsackieviruses (CVBs), protecting the body but damaging themselves. This finding suggests hepatocytes are part of the innate immune system.
Area of Science:
- Hepatology
- Virology
- Immunology
Background:
- Hepatocytes were traditionally understood to process chemical toxins, not microbial agents.
- Kupffer cells and endothelial cells were considered the primary liver cells for filtering microbes.
Purpose of the Study:
- To investigate the role of hepatocytes in viral clearance.
- To determine if hepatocytes interact with coxsackievirus-adenovirus receptor (CAR).
Main Methods:
- Utilized genetically modified mice with hepatocyte-specific CAR deletion.
- Observed viral load, hepatocyte damage, systemic disease, and mortality rates.
Main Results:
- Hepatocytes were found to trap and rapidly silence type B coxsackieviruses (CVBs).
- Hepatocyte damage occurred in wildtype mice, which was reduced in CAR-deleted mice.
- CAR-deleted mice showed increased viral load, accelerated systemic disease, and higher mortality.
Conclusions:
- Hepatocytes act as a viral sponge, sacrificing themselves to prevent systemic spread.
- This hepatocyte function may extend to other viral infections, explaining liver regeneration.
- Hepatocytes should be considered integral components of the innate immune system.
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