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Hepatitis is an inflammatory condition of the liver most commonly caused by hepatotropic viruses (A–E), though non-infectious causes such as alcohol and drugs also exist.Hepatitis AHepatitis A virus (HAV) is a non-enveloped RNA virus of the Picornaviridae family. It is primarily transmitted via the fecal-oral route, typically through ingestion of contaminated food or water. After ingestion, HAV enters the bloodstream through the oropharynx or intestinal epithelium and reaches the liver.
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Hepatitis E virus replication is maintained in proliferative cells within the intestinal crypt.

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Hepatitis E virus (HEV) primarily infects intestinal stem and progenitor cells in the gut crypts. These cells may act as reservoirs for chronic HEV infections, impacting gastrointestinal health.

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Area of Science:

  • Gastroenterology
  • Virology
  • Cell Biology

Background:

  • Hepatitis E virus (HEV) causes significant acute hepatitis globally.
  • Zoonotic HEV genotypes can lead to persistent infections in immunocompromised individuals.
  • HEV transmission occurs via the fecal-oral route, with suspected intestinal epithelial infection.

Purpose of the Study:

  • To investigate the specific cell types targeted by HEV within the intestinal epithelium.
  • To determine if intestinal stem and progenitor cells can serve as reservoirs for HEV.
  • To understand the dynamics of HEV infection and clearance in the human intestine.

Main Methods:

  • Utilized human pluripotent stem cell-derived intestinal organoids (hIOs) to model HEV infection.
  • Detected HEV RNA in intestinal crypts from an infected patient.
  • Tracked HEV spread and persistence through cell division in hIOs.

Main Results:

  • HEV predominantly infects proliferative transit-amplifying and intestinal stem cells in hIO crypts.
  • HEV RNA was confirmed in the intestinal crypts of a human patient.
  • HEV infection persisted in hIOs for over 40 days, unlike Hepatitis A virus.

Conclusions:

  • Intestinal crypts, housing proliferative progenitor cells, may serve as reservoirs for chronic HEV infection.
  • HEV utilizes the regenerative capacity of intestinal crypts for sustained infection.
  • The intestinal crypt is identified as a primary target for HEV in the gastrointestinal tract.