PMID:22379090

Citation	Arita, M, Wakita, T and Shimizu, H (2012) Valosin-containing protein (VCP/p97) is required for poliovirus replication and is involved in cellular protein secretion pathway in poliovirus infection. J. Virol. 86:5541-53
Abstract	Poliovirus (PV) modifies membrane-trafficking machinery in host cells for its viral RNA replication. To date, ARF1, ACBD3, BIG1/BIG2, GBF1, RTN3, and PI4KB have been identified as host factors of enterovirus (EV), including PV, involved in membrane traffic. In this study, we performed small interfering RNA (siRNA) screening targeting membrane-trafficking genes for host factors required for PV replication. We identified valosin-containing protein (VCP/p97) as a host factor of PV replication required after viral protein synthesis, and its ATPase activity was essential for PV replication. VCP colocalized with viral proteins 2BC/2C and 3AB/3B in PV-infected cells and showed an interaction with 2BC and 3AB but not with 2C and 3A. Knockdown of VCP did not suppress the replication of coxsackievirus B3 or Aichi virus. A VCP-knockdown-resistant PV mutant had an A4881G (a mutation of E253G in 2C) mutation, which is known as a determinant of a secretion inhibition-negative phenotype. However, knockdown of VCP did not affect the inhibition of cellular protein secretion caused by overexpression of each individual viral protein. These results suggested that VCP is a host factor required for viral RNA replication of PV among membrane-trafficking proteins and provides a novel link between cellular protein secretion and viral RNA replication.
Links	PubMed PMC3347272 Online version:10.1128/JVI.00114-12
Keywords	Adenosine Triphosphatases/genetics; Adenosine Triphosphatases/metabolism; Cell Cycle Proteins/genetics; Cell Cycle Proteins/metabolism; Cell Line; Humans; Poliomyelitis/genetics; Poliomyelitis/metabolism; Poliomyelitis/virology; Poliovirus/genetics; Poliovirus/physiology; Protein Transport; Secretory Pathway; Viral Proteins/genetics; Viral Proteins/metabolism; Virus Replication
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:TERA		GO:0019079: viral genome replication	ECO:0000315:		P		As seen in figure 6, VCP acts as a PV-specific host factor of viral replication via a cellular secretion pathway.Thus, VCP could provide a novel link between the cellular protein secretion pathway and PV replication.	complete CACAO 6890
HUMAN:TERA	involved_in	GO:0019079: viral genome replication	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

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