PHH treatment by the grapefruit flavonoid naringenin, known to inhibit MTP activity indirectly through a PPARα-mediated mechanism,
also led to a significant reduction of infectious HCV production without any detectable cytotoxic effect. Interestingly, no parallel Natural Product Library chemical structure decrease of either ApoB or ApoE secretion was observed in this case. Conclusion. These data in differentiated human hepatocytes confirm that MTP function is indeed required for production of infectious HCV, yet this requirement may not necessarily involve the role of this enzyme in ApoB lipidation. MTP inhibitors developed primarily for the treatment of lipid metabolism disorders also appear as promising host-targeting Omipalisib drugs to combat HCV infection in complement with directly acting
antivirals. Disclosures: The following people have nothing to disclose: Veronique M. Pene, Arielle R. Rosenberg Background and aims: Hepatitis E virus (HEV) is a major cause of epidemic and acute sporadic hepatitis in many developing countries. HEV is believed to undergo zoonotic transmission, with a reservoir in pigs, in industrialized countries. We have recently demonstrated in vitro infection and replication of swine HEV in primary-cultured human hepatocytes, using a genotype 3 HEV. Previous reports demonstrated that genetic changes were found in HEV progenies in the course of its habituation in human cancer line cells, which may bring change of HEV infection spectrum. Therefore, we investigated mutational events and mode of swine HEV infection and replication in the primary-cultured human hepatocytes. Methods: Hepatocytes were primary cultured from the resected normal liver of patients with metastic malignant Cyclin-dependent kinase 3 tumor using collagenase treatment, and the cultured hepatocytes were infected with HEVs (genotype 3) derived from swine. Viral replication was monitored by a strand-specific reverse transcription-polymerase chain reaction assay. Viral replication sites in cells were investigated with in situ hybridization (ISH). Immunofluorescence assay was performed using antibody against HEV 〇RF2 antigen.
In addition, the sequences of propagated and inoculated HEV were determined in order to examine whether propagation of swine HEV in the primary-cultured human hepatocytes generate base change in HEV sequence. Results: The HEV RNA increased in cultured medium as well as in cells after infection of HEV to primary-cultured human hepatocytes. ISH using cRNA of HEV as a probe demonstrated existence of genotype 3 HEV RNA in cytoplasm of hepatocytes. The immunofluorescent study revealed the following. The infected cells were found to form “infected cell clusters” and the number of the clusters do not change. However, the number of infected cells in each cluster was found to increase with the passage of culture time.