title: African swine fever virus A238L inhibitor of NF-kappaB and of calcineurin phosphatase is imported actively into the nucleus and exported by a CRM1-mediated pathway.
abstract: This study examined nuclear and cytoplasmic shuttling of the African swine fever virus (ASFV) A238L protein, which is an inhibitor of NF-kappaB and of calcineurin phosphatase. The results showed that the protein was present in both the nucleus and the cytoplasm in ASFV-infected cells and that the higher molecular mass 32 kDa form of the A238L protein was the predominant nuclear form, which accumulated later in infection. In contrast, both the 28 and 32 kDa forms of the A238L protein were present in the cytoplasm. The A238L protein was actively imported into the nucleus and exported by a CRM1-mediated pathway, although a pool of the protein remained in the cytoplasm and did not enter the nucleus. By using a recombinant ASFV from which the A238L gene had been deleted, it was shown that expression of A238L did not inhibit nuclear import of the NF-kappaB p50 or p65 subunit and did not inhibit nuclear export of p65 by a CRM1-mediated pathway. The results were consistent with a model in which A238L functions within both the nucleus and the cytoplasm.
authors.affiliation: Institute for Animal Health, Pirbright Laboratory, Ash Road, Pirbright, Woking, Surrey GU24 0NF, UK.
authors.forename: Rhiannon N
authors.initials: RN
authors.lastname: Silk
authors.affiliation: Institute for Animal Health, Pirbright Laboratory, Ash Road, Pirbright, Woking, Surrey GU24 0NF, UK.
authors.forename: Gavin C
authors.initials: GC
authors.lastname: Bowick
authors.affiliation: Institute for Animal Health, Pirbright Laboratory, Ash Road, Pirbright, Woking, Surrey GU24 0NF, UK.
authors.forename: Charles C
authors.initials: CC
authors.lastname: Abrams
authors.affiliation: Institute for Animal Health, Pirbright Laboratory, Ash Road, Pirbright, Woking, Surrey GU24 0NF, UK.
authors.forename: Linda K
authors.initials: LK
authors.lastname: Dixon
mesh_terms: D021581:Active Transport, Cell Nucleus; D000358:African Swine Fever Virus / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D002522:Chlorocebus aethiops; D003593:Cytoplasm / Q000378:metabolism*; D028884:Karyopherins / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D014709:Vero Cells; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D000097606:Exportin 1 Protein
chemical_list: D028884:Karyopherins; D016328:NF-kappa B; D010744:Phosphoric Monoester Hydrolases; D018160:Receptors, Cytoplasmic and Nuclear; D014764:Viral Proteins; D000097606:Exportin 1 Protein; C113585:A238L protein, African swine fever virus; C120817:calcineurin phosphatase