title: Inhibition of poliovirus-induced cleavage of cellular protein PCBP2 reduces the levels of viral RNA replication.
abstract: Due to their small genome size, picornaviruses must utilize host proteins to mediate cap-independent translation and viral RNA replication. The host RNA-binding protein poly(rC) binding protein 2 (PCBP2) is involved in both processes in poliovirus infected cells. It has been shown that the viral proteinase 3CD cleaves PCBP2 and contributes to viral translation inhibition. However, cleaved PCBP2 remains active in viral RNA replication. This would suggest that both cleaved and intact forms of PCBP2 have a role in the viral RNA replication cycle. The picornavirus genome must act as a template for both translation and RNA replication. However, a template that is actively being translated cannot function as a template for RNA replication, suggesting that there is a switch in template usage from translation to RNA replication. We demonstrate that the cleavage of PCBP2 by the poliovirus 3CD proteinase is a necessary step for efficient viral RNA replication and, as such, may be important for mediating a switch in template usage from translation to RNA replication.
  
  
  OBJECTIVE
  Poliovirus, like all positive-strand RNA viruses that replicate in the cytoplasm of eukaryotic cells, uses its genomic RNA as a template for both viral protein synthesis and RNA replication. Given that these processes cannot occur simultaneously on the same template, poliovirus has evolved a mechanism(s) to facilitate the switch from using templates for translation to using them for RNA synthesis. This study explores one possible scenario for how the virus alters the functions of a host cell RNA binding protein to mediate, in part, this important transition.
authors.affiliation: Department of Microbiology and Molecular Genetics, School of Medicine, University of California, Irvine, California, USA.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Chase
authors.forename: Sarah
authors.initials: S
authors.lastname: Daijogo
authors.forename: Bert L
authors.initials: BL
authors.lastname: Semler
mesh_terms: D000086042:3C Viral Proteases; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D006367:HeLa Cells; D006801:Humans; D011051:Poliomyelitis / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D017955:Poliovirus / Q000201:enzymology / Q000235:genetics* / Q000502:physiology; D011499:Protein Processing, Post-Translational; D012367:RNA, Viral / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication
chemical_list: C501903:PCBP2 protein, human; D012367:RNA, Viral; D016601:RNA-Binding Proteins; D014764:Viral Proteins; D003546:Cysteine Endopeptidases; D000086042:3C Viral Proteases