title: Poly(A)-binding protein 1 partially relocalizes to the nucleus during herpes simplex virus type 1 infection in an ICP27-independent manner and does not inhibit virus replication.
abstract: Infection of cells by herpes simplex virus type 1 (HSV-1) triggers host cell shutoff whereby mRNAs are degraded and cellular protein synthesis is diminished. However, virus protein translation continues because the translational apparatus in HSV-infected cells is maintained in an active state. Surprisingly, poly(A)-binding protein 1 (PABP1), a predominantly cytoplasmic protein that is required for efficient translation initiation, is partially relocated to the nucleus during HSV-1 infection. This relocalization occurred in a time-dependent manner with respect to virus infection. Since HSV-1 infection causes cell stress, we examined other cell stress inducers and found that oxidative stress similarly relocated PABP1. An examination of stress-induced kinases revealed similarities in HSV-1 infection and oxidative stress activation of JNK and p38 mitogen-activated protein (MAP) kinases. Importantly, PABP relocalization in infection was found to be independent of the viral protein ICP27. The depletion of PABP1 by small interfering RNA (siRNA) knockdown had no significant effect on viral replication or the expression of selected virus late proteins, suggesting that reduced levels of cytoplasmic PABP1 are tolerated during infection.
authors.affiliation: Division of Infection and Immunity, Faculty of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8TT, Scotland, United Kingdom.
authors.forename: C
authors.initials: C
authors.lastname: Salaun
authors.forename: A I
authors.initials: AI
authors.lastname: MacDonald
authors.forename: O
authors.initials: O
authors.lastname: Larralde
authors.forename: L
authors.initials: L
authors.lastname: Howard
authors.forename: K
authors.initials: K
authors.lastname: Lochtie
authors.forename: H M
authors.initials: HM
authors.lastname: Burgess
authors.forename: M
authors.initials: M
authors.lastname: Brook
authors.forename: P
authors.initials: P
authors.lastname: Malik
authors.forename: N K
authors.initials: NK
authors.lastname: Gray
authors.forename: S V
authors.initials: SV
authors.lastname: Graham
mesh_terms: D000818:Animals; D002352:Carrier Proteins; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D002522:Chlorocebus aethiops; D015967:Gene Expression Regulation, Viral; D006367:HeLa Cells; D006561:Herpes Simplex / Q000378:metabolism* / Q000821:virology; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000502:physiology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D039122:Poly(A)-Binding Protein I / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D014709:Vero Cells; D014779:Virus Replication
chemical_list: D002352:Carrier Proteins; C057120:ICP27 protein, human herpesvirus 1; D017874:Immediate-Early Proteins; D039122:Poly(A)-Binding Protein I