Nup98 Is Subverted from Annulate Lamellae by Hepatitis C Virus Core Protein to Foster Viral Assembly

Abstract

Nup98, an essential component of the nuclear pore that also participates in annulate lamella pore structures localized in the cytosol, is involved in hepatitis C virus (HCV) assembly. Here, we combined confocal microscopy and biochemical assays to study the interplay between Nup98, core (i.e., the HCV capsid protein), and viral genomes. Our results show that in HCV-infected cells, core protein is necessary and sufficient to induce relocalization of Nup98 from annulate lamellae to lipid droplet-apposed areas in which core/NS5A and HCV genomic RNA [(1)RNA] are clustered to promote viral assembly. Furthermore, we found that Nup98 interacts with HCV RNA and that upon Nup98 downregulation, the viral (1)RNA genome was specifically excluded from areas that contain active translating ribosomes and the core and NS5A proteins. Altogether, these results indicate that Nup98 is recruited by HCV core from annulate lamellae to viral assembly sites to locally increase the concentration of (1)RNA genome, which may favor its encapsidation into nascent virions.