title: Hepatitis C virus-induced cytoplasmic organelles use the nuclear transport machinery to establish an environment conducive to virus replication.
abstract: Hepatitis C virus (HCV) infection induces formation of a membranous web structure in the host cell cytoplasm where the viral genome replicates and virions assemble. The membranous web is thought to concentrate viral components and hide viral RNA from pattern recognition receptors. We have uncovered a role for nuclear pore complex proteins (Nups) and nuclear transport factors (NTFs) in the membranous web. We show that HCV infection leads to increased levels of cytoplasmic Nups that accumulate at sites enriched for HCV proteins. Moreover, we detected interactions between specific HCV proteins and both Nups and NTFs. We hypothesize that cytoplasmically positioned Nups facilitate formation of the membranous web and contribute to the compartmentalization of viral replication. Accordingly, we show that transport cargo proteins normally targeted to the nucleus are capable of entering regions of the membranous web, and that depletion of specific Nups or Kaps inhibits HCV replication and assembly.
authors.affiliation: Department of Cell Biology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Neufeldt
authors.forename: Michael A
authors.initials: MA
authors.lastname: Joyce
authors.forename: Aviad
authors.initials: A
authors.lastname: Levin
authors.forename: Rineke H
authors.initials: RH
authors.lastname: Steenbergen
authors.forename: Daniel
authors.initials: D
authors.lastname: Pang
authors.forename: Justin
authors.initials: J
authors.lastname: Shields
authors.forename: D Lorne J
authors.initials: DL
authors.lastname: Tyrrell
authors.forename: Richard W
authors.initials: RW
authors.lastname: Wozniak
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000235:genetics; D002460:Cell Line; D016174:Hepacivirus / Q000502:physiology*; D006526:Hepatitis C / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism* / Q000821:virology; D022022:Nuclear Pore / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D014779:Virus Replication / Q000502:physiology*