title: CNS activity of Pokeweed anti-viral protein (PAP) in mice infected with lymphocytic choriomeningitis virus (LCMV).
abstract: BACKGROUND
  Others and we have previously described the potent in vivo and in vitro activity of the broad-spectrum antiviral agent PAP (Pokeweed antiviral protein) against a wide range of viruses. The purpose of the present study was to further elucidate the anti-viral spectrum of PAP by examining its effects on the survival of mice challenged with lymphocytic choriomeningitis virus (LCMV).
  
  
  METHODS
  We examined the therapeutic effect of PAP in CBA mice inoculated with intracerebral injections of the WE54 strain of LCMV at a 1000 PFU dose level that is lethal to 100% of mice within 7-9 days. Mice were treated either with vehicle or PAP administered intraperitoneally 24 hours prior to, 1 hour prior to and 24 hours, 48 hours 72 hours and 96 hours after virus inoculation.
  
  
  RESULTS
  PAP exhibits significant in vivo anti- LCMV activity in mice challenged intracerebrally with an otherwise invariably fatal dose of LCMV. At non-toxic dose levels, PAP significantly prolonged survival in the absence of the majority of disease-associated symptoms. The median survival time of PAP-treated mice was >21 days as opposed to 7 days median survival for the control (p = 0.0069).
  
  
  CONCLUSIONS
  Our results presented herein provide unprecedented experimental evidence that PAP exhibits antiviral activity in the CNS of LCMV-infected mice.
authors.affiliation: Parker Hughes Center for Clinical Immunology, St, Paul, MN 55113, USA. fatih_uckun@ih.org
authors.forename: Fatih M
authors.initials: FM
authors.lastname: Uckun
authors.forename: Larisa
authors.initials: L
authors.lastname: Rustamova
authors.forename: Alexei O
authors.initials: AO
authors.lastname: Vassilev
authors.forename: Heather E
authors.initials: HE
authors.lastname: Tibbles
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Petkevich
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001921:Brain / Q000378:metabolism / Q000821:virology*; D004195:Disease Models, Animal; D008216:Lymphocytic Choriomeningitis / Q000188:drug therapy*; D008217:Lymphocytic choriomeningitis virus / Q000187:drug effects; D051379:Mice; D008808:Mice, Inbred CBA; D009699:N-Glycosyl Hydrolases / Q000494:pharmacology / Q000627:therapeutic use*; D010940:Plant Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D054789:Ribosome Inactivating Proteins, Type 1
chemical_list: D000998:Antiviral Agents; D010940:Plant Proteins; D011500:Protein Synthesis Inhibitors; D054789:Ribosome Inactivating Proteins, Type 1; D009699:N-Glycosyl Hydrolases; C024275:pokeweed antiviral protein
references.citation: Blood. 1992 May 1;79(9):2201-14
references.pmid: 1373967
references.citation: Blood. 1992 May 15;79(10):2649-61
references.pmid: 1375109
references.citation: Blood. 1992 Jun 15;79(12):3116-29
references.pmid: 1375841
references.citation: Blood. 1992 Jun 15;79(12):3369-79
references.pmid: 1375851
references.citation: Int J Immunopharmacol. 1991;13 Suppl 1:63-8
references.pmid: 1688086
references.citation: Leukemia. 1993 Feb;7(2):290-7
references.pmid: 7678881
references.citation: Leukemia. 1993 Feb;7(2):298-309
references.pmid: 7678882
references.citation: Pharmacol Ther. 1992;55(3):279-302
references.pmid: 1492120
references.citation: Antimicrob Agents Chemother. 1993 Apr;37(4):835-8
references.pmid: 8494381
references.citation: Leuk Lymphoma. 1993 Apr;9(6):459-76
references.pmid: 7687916
references.citation: Cancer Res. 1995 Mar 15;55(6):1321-7
references.pmid: 7882330
references.citation: Blood. 1995 May 1;85(9):2537-45
references.pmid: 7537120
references.citation: Proc Natl Acad Sci U S A. 1995 Aug 29;92(18):8448-52
references.pmid: 7667309
references.citation: Blood. 1995 Dec 1;86(11):4228-33
references.pmid: 7492781
references.citation: Leuk Lymphoma. 1995 Jun;18(1-2):93-102
references.pmid: 8580835
references.citation: Leuk Lymphoma. 1996 Jun;22(1-2):61-70, follow.186, color plate II-V
references.pmid: 8724529
references.citation: Nat Biotechnol. 1997 Oct;15(10):992-6
references.pmid: 9335052
references.citation: Leuk Lymphoma. 1997 Oct;27(3-4):275-302
references.pmid: 9402326
references.citation: Antimicrob Agents Chemother. 1998 Feb;42(2):383-8
references.pmid: 9527790
references.citation: Clin Cancer Res. 1998 Jul;4(7):1641-7
references.pmid: 9676838
references.citation: Clin Cancer Res. 1997 Mar;3(3):325-37
references.pmid: 9815689
references.citation: Science. 1998 Dec 11;282(5396):2079-81
references.pmid: 9851928
references.citation: J Pharmacol Exp Ther. 1999 Dec;291(3):1301-7
references.pmid: 10565855
references.citation: Protein Sci. 1999 Nov;8(11):2399-405
references.pmid: 10595542
references.citation: J Biol Chem. 2000 Feb 4;275(5):3382-90
references.pmid: 10652330
references.citation: Protein Expr Purif. 2000 Mar;18(2):193-201
references.pmid: 10686150
references.citation: Pediatrics. 2000 Mar;105(3):E35
references.pmid: 10699137
references.citation: Virology. 2000 Apr 10;269(2):248-56
references.pmid: 10753703
references.citation: Blood Coagul Fibrinolysis. 2000 Jul;11(5):461-83
references.pmid: 10937808
references.citation: Biochem Biophys Res Commun. 2000 Aug 28;275(2):549-52
references.pmid: 10964701
references.citation: J Virol. 2001 Jan;75(1):448-57
references.pmid: 11119613
references.citation: Fertil Steril. 2001 Jan;75(1):106-14
references.pmid: 11163824
references.citation: J Biol Chem. 2001 Jun 29;276(26):24075-81
references.pmid: 11313342
references.citation: Biochemistry. 2001 Aug 7;40(31):9104-14
references.pmid: 11478877
references.citation: HIV Med. 2001 Apr;2(2):97-104
references.pmid: 11737386
references.citation: J Neurovirol. 2002 Jun;8(3):158-67
references.pmid: 12053271
references.citation: J Pediatr. 2002 Jul;141(1):36-44
references.pmid: 12091849
references.citation: RNA. 2002 Sep;8(9):1148-59
references.pmid: 12358434
references.citation: Antimicrob Agents Chemother. 2003 Mar;47(3):1052-61
references.pmid: 12604541
references.citation: Biochem Pharmacol. 2003 May 15;65(10):1709-17
references.pmid: 12754107
references.citation: J Virol. 2003 Sep;77(18):9733-7
references.pmid: 12941881
references.citation: Nat Rev Immunol. 2003 Aug;3(8):677-85
references.pmid: 12974482
references.citation: Emerg Infect Dis. 2004 Jan;10(1):40-7
references.pmid: 15078595
references.citation: Mini Rev Med Chem. 2004 Jun;4(5):523-43
references.pmid: 15180509
references.citation: Phytomedicine. 2004;11(4):342-51
references.pmid: 15185849
references.citation: Blut. 1985 Jan;50(1):19-23
references.pmid: 3881146
references.citation: J Immunol. 1985 Nov;135(5):3616-22
references.pmid: 3900212
references.citation: J Exp Med. 1986 Feb 1;163(2):347-68
references.pmid: 3511171
references.citation: J Immunol Methods. 1991 Feb 15;136(2):221-37
references.pmid: 1705571
references.citation: Clin Cancer Res. 1997 Jun;3(6):881-90
references.pmid: 9815763
references.citation: J Neurovirol. 1999 Feb;5(1):65-75
references.pmid: 10190692
references.citation: Biochem Biophys Res Commun. 1999 Jul 5;260(2):453-8
references.pmid: 10403789
references.citation: Protein Expr Purif. 1999 Jul;16(2):359-68
references.pmid: 10419833
references.citation: Protein Sci. 1999 Sep;8(9):1765-72
references.pmid: 10493577
references.citation: Biochem Biophys Res Commun. 1999 Sep 24;263(2):419-24
references.pmid: 10491308