Valosin-Containing Protein (VCP/p97) Is Required for Poliovirus Replication and Is Involved in Cellular Protein Secretion Pathway in Poliovirus Infection
Open Access
- 15 May 2012
- journal article
- research article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 86 (10), 5541-5553
- https://doi.org/10.1128/jvi.00114-12
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.Keywords
This publication has 122 references indexed in Scilit:
- ACBD3-mediated recruitment of PI4KB to picornavirus RNA replication sitesThe EMBO Journal, 2011
- Viral Reorganization of the Secretory Pathway Generates Distinct Organelles for RNA ReplicationCell, 2010
- Valosin-containing protein (VCP) is required for autophagy and is disrupted in VCP diseaseThe Journal of cell biology, 2009
- Roles for endocytic trafficking and phosphatidylinositol 4-kinase III alpha in hepatitis C virus replicationProceedings of the National Academy of Sciences of the United States of America, 2009
- Impaired Protein Aggregate Handling and Clearance Underlie the Pathogenesis of p97/VCP-associated DiseaseJournal of Biological Chemistry, 2008
- Direct observation of individual endogenous protein complexes in situ by proximity ligationNature Methods, 2006
- Inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia is caused by mutant valosin-containing proteinNature Genetics, 2004
- Distinct Roles for the AAA ATPases NSF and p97 in the Secretory PathwayMolecular Biology of the Cell, 2004
- Brefeldin A Acts to Stabilize an Abortive ARF–GDP–Sec7 Domain Protein Complex: Involvement of Specific Residues of the Sec7 DomainMolecular Cell, 1999
- Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4Nature, 1970