CNS activity of Pokeweed anti-viral protein (PAP) in mice infected with lymphocytic choriomeningitis virus (LCMV).
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.
Uckun
Fatih M
FM
Parker Hughes Center for Clinical Immunology, St, Paul, MN 55113, USA. fatih_uckun@ih.org
Rustamova
Larisa
L
Vassilev
Alexei O
AO
Tibbles
Heather E
HE
Petkevich
Alexander S
AS
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
D000998:Antiviral Agents; D010940:Plant Proteins; D011500:Protein Synthesis Inhibitors; D054789:Ribosome Inactivating Proteins, Type 1; D009699:N-Glycosyl Hydrolases; C024275:pokeweed antiviral protein
Blood. 1992 May 1;79(9):2201-14
1373967
Blood. 1992 May 15;79(10):2649-61
1375109
Blood. 1992 Jun 15;79(12):3116-29
1375841
Blood. 1992 Jun 15;79(12):3369-79
1375851
Int J Immunopharmacol. 1991;13 Suppl 1:63-8
1688086
Leukemia. 1993 Feb;7(2):290-7
7678881
Leukemia. 1993 Feb;7(2):298-309
7678882
Pharmacol Ther. 1992;55(3):279-302
1492120
Antimicrob Agents Chemother. 1993 Apr;37(4):835-8
8494381
Leuk Lymphoma. 1993 Apr;9(6):459-76
7687916
Cancer Res. 1995 Mar 15;55(6):1321-7
7882330
Blood. 1995 May 1;85(9):2537-45
7537120
Proc Natl Acad Sci U S A. 1995 Aug 29;92(18):8448-52
7667309
Blood. 1995 Dec 1;86(11):4228-33
7492781
Leuk Lymphoma. 1995 Jun;18(1-2):93-102
8580835
Leuk Lymphoma. 1996 Jun;22(1-2):61-70, follow.186, color plate II-V
8724529
Nat Biotechnol. 1997 Oct;15(10):992-6
9335052
Leuk Lymphoma. 1997 Oct;27(3-4):275-302
9402326
Antimicrob Agents Chemother. 1998 Feb;42(2):383-8
9527790
Clin Cancer Res. 1998 Jul;4(7):1641-7
9676838
Clin Cancer Res. 1997 Mar;3(3):325-37
9815689
Science. 1998 Dec 11;282(5396):2079-81
9851928
J Pharmacol Exp Ther. 1999 Dec;291(3):1301-7
10565855
Protein Sci. 1999 Nov;8(11):2399-405
10595542
J Biol Chem. 2000 Feb 4;275(5):3382-90
10652330
Protein Expr Purif. 2000 Mar;18(2):193-201
10686150
Pediatrics. 2000 Mar;105(3):E35
10699137
Virology. 2000 Apr 10;269(2):248-56
10753703
Blood Coagul Fibrinolysis. 2000 Jul;11(5):461-83
10937808
Biochem Biophys Res Commun. 2000 Aug 28;275(2):549-52
10964701
J Virol. 2001 Jan;75(1):448-57
11119613
Fertil Steril. 2001 Jan;75(1):106-14
11163824
J Biol Chem. 2001 Jun 29;276(26):24075-81
11313342
Biochemistry. 2001 Aug 7;40(31):9104-14
11478877
HIV Med. 2001 Apr;2(2):97-104
11737386
J Neurovirol. 2002 Jun;8(3):158-67
12053271
J Pediatr. 2002 Jul;141(1):36-44
12091849
RNA. 2002 Sep;8(9):1148-59
12358434
Antimicrob Agents Chemother. 2003 Mar;47(3):1052-61
12604541
Biochem Pharmacol. 2003 May 15;65(10):1709-17
12754107
J Virol. 2003 Sep;77(18):9733-7
12941881
Nat Rev Immunol. 2003 Aug;3(8):677-85
12974482
Emerg Infect Dis. 2004 Jan;10(1):40-7
15078595
Mini Rev Med Chem. 2004 Jun;4(5):523-43
15180509
Phytomedicine. 2004;11(4):342-51
15185849
Blut. 1985 Jan;50(1):19-23
3881146
J Immunol. 1985 Nov;135(5):3616-22
3900212
J Exp Med. 1986 Feb 1;163(2):347-68
3511171
J Immunol Methods. 1991 Feb 15;136(2):221-37
1705571
Clin Cancer Res. 1997 Jun;3(6):881-90
9815763
J Neurovirol. 1999 Feb;5(1):65-75
10190692
Biochem Biophys Res Commun. 1999 Jul 5;260(2):453-8
10403789
Protein Expr Purif. 1999 Jul;16(2):359-68
10419833
Protein Sci. 1999 Sep;8(9):1765-72
10493577
Biochem Biophys Res Commun. 1999 Sep 24;263(2):419-24
10491308