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.

The separation of virus replication and assembly implies that host proteins required for these processes are present in in the microsomal and MAM fractions. We examined the location of several host proteins known to function during either viral replication or virion assembly. Previous studies have implicated Apolipoprotien E (ApoE) in viral assembly and 1-phosphatidylinositol 4-kinase (PI4K) in viral replication [53] [54] [55] [56] . Therefore, we probed membrane fractions derived from infected cells with antibodies directed against ApoE and PI4K ( Fig 4B) . As shown in Fig 4C, ApoE is present in the MAM fraction, which is consistent with the conclusion that this fraction is enriched for viral assembly complexes. Additionally, we show that PI4K is primarily found in the microsomal fraction. These observations are consistent with the microsomal fraction being enriched for viral replication complexes.