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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.<\/jats:p>","DOI":"10.1128\/jvi.00114-12","type":"journal-article","created":{"date-parts":[[2012,3,1]],"date-time":"2012-03-01T02:41:17Z","timestamp":1330569677000},"page":"5541-5553","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":67,"title":["Valosin-Containing Protein (VCP\/p97) Is Required for Poliovirus Replication and Is Involved in Cellular Protein Secretion Pathway in Poliovirus Infection"],"prefix":"10.1128","volume":"86","author":[{"given":"Minetaro","family":"Arita","sequence":"first","affiliation":[{"name":"Department of Virology II, National Institute of Infectious Diseases, Musashimurayama-shi, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takaji","family":"Wakita","sequence":"additional","affiliation":[{"name":"Department of Virology II, National Institute of Infectious Diseases, Musashimurayama-shi, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Department of Virology II, National Institute of Infectious Diseases, Musashimurayama-shi, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01798-07"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.2.1066-1074.1999"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02249-10"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.82172-0"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.023374-0"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.012096-0"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.2008\/002915-0"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.20.12650-12657.2005"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.2174\/138161206776361129"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.71.11.8482-8489.1997"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000216"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00840-07"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2010.01482.x"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0902693106"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.62.8.2922-2928.1988"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.64.3.1156-1163.1990"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(49)90130-8"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1007\/s007050050611"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00642-09"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6822(68)90219-5"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkn424"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.0020102"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2005.03.036"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2008.04.002"},{"key":"e_1_3_3_26_2","unstructured":"Committee on Development of a Polio Antiviral and Its Potential Role in Global Poliomyelitis Eradication National Research Council. 2006. 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