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Requirement of cellular DDX3 for hepatitis C virus replication is unrelated to its interaction with the viral core protein. | LitMetric

AI Article Synopsis

  • The study confirms that the DEAD-box protein DDX3 is crucial for the replication of the hepatitis C virus (HCV), and its interaction with HCV core protein was verified through co-immunoprecipitation in cells.
  • Immunofluorescence staining of infected cells showed that DDX3 is redistributed to virus assembly sites, suggesting a significant role in the virus life cycle.
  • Interestingly, while a specific mutation in the HCV core protein disrupted its interaction with DDX3, it did not affect virus production or RNA replication, indicating that DDX3's role in HCV replication is independent of its interaction with the viral core.

Article Abstract

The cellular DEAD-box protein DDX3 was recently shown to be essential for hepatitis C virus (HCV) replication. Prior to that, we had reported that HCV core binds to DDX3 in yeast-two hybrid and transient transfection assays. Here, we confirm by co-immunoprecipitation that this interaction occurs in cells replicating the JFH1 virus. Consistent with this result, immunofluorescence staining of infected cells revealed a dramatic redistribution of cytoplasmic DDX3 by core protein to the virus assembly sites around lipid droplets. Given this close association of DDX3 with core and lipid droplets, and its involvement in virus replication, we investigated the importance of this host factor in the virus life cycle. Mutagenesis studies located a single amino acid in the N-terminal domain of JFH1 core that when changed to alanine significantly abrogated this interaction. Surprisingly, this mutation did not alter infectious virus production and RNA replication, indicating that the core-DDX3 interaction is dispensable in the HCV life cycle. Consistent with previous studies, siRNA-led knockdown of DDX3 lowered virus production and RNA replication levels of both WT JFH1 and the mutant virus unable to bind DDX3. Thus, our study shows for the first time that the requirement of DDX3 for HCV replication is unrelated to its interaction with the viral core protein.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2885062PMC
http://dx.doi.org/10.1099/vir.0.015909-0DOI Listing

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