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.

Although there are significant differences in the organization and architecture of the membrane rearrangements induced by positive-strand RNA viruses, the general functions of these compartments are predicted to be conserved. Like HCV, we observed that RIG-I is also inhibited from accessing replication factories produced by HAV, which induces a perinuclear tubular-vesicular membrane replication complex. Similarly, previous studies have shown that viral replication factories produced in Tick-borne encephalitis virus-infected cells (invaginated vesicle or spherule-type) inhibit immune activation by concealing viral dsRNA from cytosolic RLRs [36] . Collectively, these observations support the conclusions that, despite their apparent structural variability, membrane rearrangements induced by different positive-strand RNA viruses are likely to perform a universal function of concealing PAMPs from host RLRs as a means of immune evasion. Moreover, the presence of nuclear pore complex components within membrane structures induced by HAV and Dengue virus lead us to conclude that the nuclear transport machinery may be commonly employed to regulate the movement of molecules into and out of compartments formed by these membrane structures [37] .