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.

Previously, we have shown that components of the nuclear pore complex (NPC) redistribute to regions of HCV replication and assembly within the MW, and we provided evidence supporting a role for the nuclear transport machinery in the formation and function of the MW [37, 38] . Comprised of~30 distinct proteins, termed nucleoporins (Nups), the NPC is a large macromolecular structure that facilitates bidirectional transport of macromolecules across the nuclear envelope between the cytoplasm and nucleoplasm. Transport through the NPC is mediated by soluble nuclear transport factors, many of which are members of a family of proteins termed karyopherins. Some karyopherins function in nuclear import (importins), while others export molecules from the nucleus (exportins). Cargos destined for the nucleoplasm contain short amino acid sequences termed nuclear localization signals (NLSs) that bind importins, while molecules exported from the nucleus contain nuclear export signals (NESs) that bind exportins. The resulting karyopherin-cargo complexes can then move through the NPC (reviewed in [39] ).