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Hepatitis E virus replication is maintained in proliferative cells within the intestinal crypt
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DOI：10.1126/sciadv.aeb2333.png)
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Abstract
En 中文
The hepatitis E virus (HEV) is a leading cause of acute hepatitis worldwide. Although most infections are self-limiting, zoonotic genotypes can persist in immunocompromised individuals. Transmitted via the fecal-oral route, HEV has been suggested to directly infect the intestinal epithelium, a tissue with high regenerative capacity. Here, we demonstrate that HEV predominantly infects proliferative transit-amplifying and intestinal stem cells within the crypts of human pluripotent stem cell–derived intestinal organoids (hIOs). Supporting this, we detected HEV RNA in the intestinal crypts of an HEV-infected patient. We further found that HEV infection spreads through cell division and is maintained in hIOs for more than 40 days, contrasting with acute hepatitis A virus, whose infections are rapidly cleared from hIOs. Given the self-renewal ability and metabolic constraints of proliferative intestinal progenitor cells, our findings suggest that intestinal crypts could serve as reservoirs for chronic HEV infection and highlight the intestinal crypt as a primary target for viral infection in the gastrointestinal tract.
Keywords:
Hepatitis E virus
intestinal crypt
proliferative cells
viral reservoir
stem cells
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