Shift of hepatitis E virus RNA from hepatocytes to biliary epithelial cells during acute infection of rhesus monkey

Hepatitis E virus (HEV) has been considered to be the major cause of enteri cally transmitted non-A, non-B hepatitis in developing countries, However, little is known about viral replication and localization in the liver. The aim of this study was to examine the distribution of HEV-infected cells in experimentally infected animals. Seven captured wild rhesus monkeys were in oculated intravenously with faecal extract derived from a Myanmar strain of HEV. Animals were killed at different time-points of clinical illness: dur ing early infection, during prehepatitis with viral-like particles in bile, during acute hepatitis and during convalescence. Intrahepatic localization of HEV was analysed using non-isotopic thymine dimer in situ hybridization (NIT-DISH). Both plus and minus strands of HEV RNA were found in hepatocyt es during the early infection period. Staining in the submembranous cytopla smic region of hepatocytes was observed. In the prehepatitis period, both p lus and minus strand HEV RNAs appeared in the canalicular side of isolated bile epithelial cells, Subsequently, HEV RNA became universally distributed in the cytoplasm of medium-size bile epithelial cells, After recovery, HEV RNA disappeared.