title: Identification of residues within the African swine fever virus DP71L protein required for dephosphorylation of translation initiation factor eIF2α and inhibiting activation of pro-apoptotic CHOP.
abstract: The African swine fever virus DP71L protein recruits protein phosphatase 1 (PP1) to dephosphorylate the translation initiation factor 2α (eIF2α) and avoid shut-off of global protein synthesis and downstream activation of the pro-apoptotic factor CHOP. Residues V16 and F18A were critical for binding of DP71L to PP1. Mutation of this PP1 binding motif or deletion of residues between 52 and 66 reduced the ability of DP71L to cause dephosphorylation of eIF2α and inhibit CHOP induction. The residues LSAVL, between 57 and 61, were also required. PP1 was co-precipitated with wild type DP71L and the mutant lacking residues 52- 66 or the LSAVL motif, but not with the PP1 binding motif mutant. The residues in the LSAVL motif play a critical role in DP71L function but do not interfere with binding to PP1. Instead we propose these residues are important for DP71L binding to eIF2α.
authors.affiliation: The Pirbright Institute, Ash Road, Pirbright, Woking, Surrey GU24 0NF, United Kingdom.
authors.forename: Claire
authors.initials: C
authors.lastname: Barber
authors.affiliation: The Pirbright Institute, Ash Road, Pirbright, Woking, Surrey GU24 0NF, United Kingdom.
authors.forename: Chris
authors.initials: C
authors.lastname: Netherton
authors.affiliation: The Pirbright Institute, Ash Road, Pirbright, Woking, Surrey GU24 0NF, United Kingdom.
authors.forename: Lynnette
authors.initials: L
authors.lastname: Goatley
authors.affiliation: Institute for Infection and Immunity, St. George's, University of London, London SW17 0RE, United Kingdom.
authors.forename: Alice
authors.initials: A
authors.lastname: Moon
authors.affiliation: Institute for Infection and Immunity, St. George's, University of London, London SW17 0RE, United Kingdom.
authors.forename: Steve
authors.initials: S
authors.lastname: Goodbourn
authors.affiliation: The Pirbright Institute, Ash Road, Pirbright, Woking, Surrey GU24 0NF, United Kingdom. Electronic address: linda.dixon@pirbright.ac.uk.
authors.forename: Linda
authors.initials: L
authors.lastname: Dixon
mesh_terms: D000358:African Swine Fever Virus / Q000235:genetics*; D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D001665:Binding Sites / Q000235:genetics; D002522:Chlorocebus aethiops; D004789:Enzyme Activation / Q000187:drug effects / Q000235:genetics; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D011485:Protein Binding / Q000235:genetics; D054645:Protein Phosphatase 1 / Q000378:metabolism*; D051742:Transcription Factor CHOP / Q000378:metabolism; D014415:Tunicamycin / Q000494:pharmacology; D014709:Vero Cells; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D015852:Eukaryotic Initiation Factor-2; D014764:Viral Proteins; D014415:Tunicamycin; D051742:Transcription Factor CHOP; D054645:Protein Phosphatase 1
keywords: African swine fever virus; CHOP; EIF2α; Protein translation; Unfolded protein response