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.

An important corollary that arises from our detection of RLR exclusion from the MW is that the localization of RLRs in HCV-infected cells provides a useful exclusion marker for the MW. Ours and numerous previous studies using either electron microscopy or immunofluorescence microscopy have outlined the complexity of the MW and demonstrated the difficulties in defining the MW using individual viral or host protein markers (Fig 1) [8, 21, 23, 73, 74] . Based on the results presented in this study, we suggest that regions of functional compartmentalization within the MW can be more accurately defined by both the presence of specific HCV proteins or viral RNA, and the exclusion of RLRs (defined by ectopically expressed RIG-I-K270A), bulk ribosomes, and tubulin (Figs 1, 3 and 5). We predict that defining these regions of the MW can provide an important tool for the analysis host factors and their role in the viral life cycle.