title: Regulation of Viral RNA Synthesis by the V Protein of Parainfluenza Virus 5.
abstract: Paramyxoviruses include many important animal and human pathogens. The genome of parainfluenza virus 5 (PIV5), a prototypical paramyxovirus, encodes a V protein that inhibits viral RNA synthesis. In this work, the mechanism of inhibition was investigated. Using mutational analysis and a minigenome system, we identified regions in the N and C termini of the V protein that inhibit viral RNA synthesis: one at the very N terminus of V and the second at the C terminus of V. Furthermore, we determined that residues L16 and I17 are critical for the inhibitory function of the N-terminal region of the V protein. Both regions interact with the nucleocapsid protein (NP), an essential component of the viral RNA genome complex (RNP). Mutations at L16 and I17 abolished the interaction between NP and the N-terminal domain of V. This suggests that the interaction between NP and the N-terminal domain plays a critical role in V inhibition of viral RNA synthesis by the N-terminal domain. Both the N- and C-terminal regions inhibited viral RNA replication. The C terminus inhibited viral RNA transcription, while the N-terminal domain enhanced viral RNA transcription, suggesting that the two domains affect viral RNA through different mechanisms. Interestingly, V also inhibited the synthesis of the RNA of other paramyxoviruses, such as Nipah virus (NiV), human parainfluenza virus 3 (HPIV3), measles virus (MeV), mumps virus (MuV), and respiratory syncytial virus (RSV). This suggests that a common host factor may be involved in the replication of these paramyxoviruses.
  
  
  OBJECTIVE
  We identified two regions of the V protein that interact with NP and determined that one of these regions enhances viral RNA transcription via its interaction with NP. Our data suggest that a common host factor may be involved in the regulation of paramyxovirus replication and could be a target for broad antiviral drug development. Understanding the regulation of paramyxovirus replication will enable the rational design of vaccines and potential antiviral drugs.
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei, China Department of Infectious Diseases, University of Georgia College of Veterinary Medicine, Athens, Georgia, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Infectious Diseases, University of Georgia College of Veterinary Medicine, Athens, Georgia, USA.
authors.forename: James
authors.initials: J
authors.lastname: Zengel
authors.affiliation: Graduate Program in Pathobiology, Pennsylvania State University, University Park, Pennsylvania, USA.
authors.forename: Minghao
authors.initials: M
authors.lastname: Sun
authors.affiliation: National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Katrina
authors.initials: K
authors.lastname: Sleeman
authors.affiliation: Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, Pennsylvania, USA.
authors.forename: Khalid Amine
authors.initials: KA
authors.lastname: Timani
authors.affiliation: Intercollege Graduate Program in Genetics, Pennsylvania State University, University Park, Pennsylvania, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Aligo
authors.affiliation: National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Rota
authors.affiliation: State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei, China jwu@whu.edu.cn bhe@uag.edu.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Infectious Diseases, University of Georgia College of Veterinary Medicine, Athens, Georgia, USA Graduate Program in Pathobiology, Pennsylvania State University, University Park, Pennsylvania, USA Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, Pennsylvania, USA jwu@whu.edu.cn bhe@uag.edu.
authors.forename: Biao
authors.initials: B
authors.lastname: He
mesh_terms: D015153:Blotting, Western; D017931:DNA Primers / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D047468:Immunoprecipitation; D018613:Microscopy, Confocal; D019590:Nucleocapsid Proteins / Q000378:metabolism; D045402:Parainfluenza Virus 5 / Q000235:genetics* / Q000502:physiology; D012367:RNA, Viral / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D019590:Nucleocapsid Proteins; D012367:RNA, Viral; C068854:V protein, human parainfluenza virus type 1; D014764:Viral Proteins