Hepatitis E virus replication is maintained in proliferative cells within the intestinal crypt

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.