Rapid and efficient clearance of blood-borne virus by liver sinusoidal endothelium

PLoS Pathog. 2011 Sep;7(9):e1002281. doi: 10.1371/journal.ppat.1002281. Epub 2011 Sep 29.


The liver removes quickly the great bulk of virus circulating in blood, leaving only a small fraction to infect the host, in a manner characteristic of each virus. The scavenger cells of the liver sinusoids are implicated, but the mechanism is entirely unknown. Here we show, borrowing a mouse model of adenovirus clearance, that nearly all infused adenovirus is cleared by the liver sinusoidal endothelial cell (LSEC). Using refined immunofluorescence microscopy techniques for distinguishing macrophages and endothelial cells in fixed liver, and identifying virus by two distinct physicochemical methods, we localized adenovirus 1 minute after infusion mainly to the LSEC (∼90%), finding ∼10% with Kupffer cells (KC) and none with hepatocytes. Electron microscopy confirmed our results. In contrast with much prior work claiming the main scavenger to be the KC, our results locate the clearance mechanism to the LSEC and identify this cell as a key site of antiviral activity.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenoviridae / immunology
  • Adenoviridae / metabolism*
  • Adenoviridae / ultrastructure
  • Adenoviridae Infections / immunology
  • Adenoviridae Infections / metabolism*
  • Animals
  • Blood-Borne Pathogens*
  • Cells, Cultured
  • Endothelium, Vascular / immunology
  • Endothelium, Vascular / metabolism*
  • Endothelium, Vascular / ultrastructure
  • Endothelium, Vascular / virology
  • Hepatocytes / immunology
  • Hepatocytes / metabolism
  • Hepatocytes / ultrastructure
  • Hepatocytes / virology
  • Humans
  • Kupffer Cells / immunology
  • Kupffer Cells / metabolism
  • Kupffer Cells / ultrastructure
  • Kupffer Cells / virology
  • Liver / immunology
  • Liver / metabolism*
  • Liver / ultrastructure
  • Liver / virology
  • Mice
  • Mice, Inbred BALB C