Examination of potential inhibitors of hepatitis A virus uncoating

Naomi Bishop, Naomi E. Bishop

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Hepatitis A virus (HAV) replication in BS-C-1 cells was studied in the presence of ten potential uncoating inhibitors. Strong inhibition of HAV replication was only observed in the presence of the phenothiazine compound chlorpromazine and the lysosomotropic agent chloroquine, but not by other lysosomotropic agents. Chlorpromazine and chloroquine were found to prevent virus uncoating. Chlorpromazine is known to inhibit endocytosis of non-clathrin-coated vesicles. Chloroquine is a weak base amine, and thought to inhibit virus replication by preventing endosomal acidification. These results therefore suggest that entry of HAV in BS-C-1 cells does not depend on the low pH encountered in the clathrin-coated endocytic entry pathway. A possible role of calcium ions in mediating viral uncoating is discussed, as calcium ions were found to destabilize HAV particles in vitro.
    Original languageEnglish
    Pages (from-to)261-271
    Number of pages10
    JournalIntervirology
    Volume41
    Issue number6
    Publication statusPublished - 1998

    Keywords

    • Chloroquine
    • Chlorpromazine
    • Endocytosis
    • Hepatitis A virus
    • Lysosomotropic agents
    • Uncoating

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