The Hepatitis C Virus-Induced Membranous Web and Associated Nuclear Transport Machinery Limit Access of Pattern Recognition Receptors to Viral Replication Sites

Neufeldt, Christopher J.; Joyce, Michael A.; Van Buuren, Nicholas; Levin, Aviad; Kirkegaard, Karla; Gale Jr., Michael; Tyrrell, D. Lorne J.; Wozniak, Richard W.

Many viral proteins interact with components of the NPC or nuclear transport pathway (reviewed in [40, 41] ). In most cases, these interactions reflect either a nuclear phase of the viral infection or a host-viral protein interaction that alters nuclear transport pathways. However, in the case of HCV, previous data indicate a cytoplasmic role for the nuclear transport machinery in infected cells [37] . In this work, a model was proposed in which NPC-like structures present within the MW facilitate transport between compartments within the MW and the surrounding cytosol in HCV-infected cells. This model predicts that NLS sequences found in certain proteins, including the viral proteins Core, NS2, NS3, and NS5A, as well as nuclear factors, are important for allowing access to the MW, while other proteins lacking NLSs, such as RLRs, are inhibited from entry [42, 43] . The use of NPC-mediated transport between cytoplasmic compartments in HCV-infected cells may constitute an important mechanism by which HCV evades RLR activation while maintaining active replication complexes.