Hepatitis C Virus-Induced Cytoplasmic Organelles Use the Nuclear Transport Machinery to Establish an Environment Conducive to Virus Replication: e1003744

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...

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Bibliographic Details
Published in:PLoS pathogens 2013-10, Vol.9 (10)
Main Authors: Neufeldt, Christopher J, Joyce, Michael A, Levin, Aviad, Steenbergen, Rineke H, Pang, Daniel, Shields, Justin, Tyrrell, D LorneJ, Wozniak, Richard W
Format: Article
Language:English
Subjects:
Cytoplasm
Genomes
Hepatitis
Hepatitis C virus
Infections
Liver diseases
Machinery
Medical research
Membranes
Microbiology
Microscopy
Pattern recognition
Peptides
Proteins
Viral infections
Viruses
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Summary: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.
ISSN:1553-7366
1553-7374
DOI:10.1371/journal.ppat.1003744