Effect of interferon-alpha and interferon-inducers on West Nile virus in mouse and hamster animal models.
The recent West Nile virus (WNV) outbreak in the United States has increased the need to identify effective therapies. Studies were conducted in cell culture and in rodent animal models to determine the efficacy of interferon-alpha (IFN-alpha), interferon (IFN) inducers and ribavirin, alone or in combination with IFN, in treating WNV. Intraperitoneal injection of IFN-alpha B/D (qd for 7 days), polyI-polyC(12)U [Ampligen (every other day for 7 days)] and topically applied imiquimod (qd for 7 days), administered from 1 day before viral challenge, were effective in protecting, respectively, 100%, 100% and 70% of BALB/c mice from mortality induced by subcutaneous injection of WNV. When IFN-alpha B/D or Ampligen treatments were delayed to 4-6 h before viral challenge in mice, efficacy was greatly diminished. Infected Syrian golden hamsters treated with interferon alphacon-1 (Infergen) and Ampligen 4-6 h before viral challenge gained more weight and had a greater survival than saline-treated animals. A combination study of subcutaneously administered Infergen (5 to 0.05 microg/kg/day) and ribavirin (75 to 7.5 mg/kg/day) in >7 week old hamsters demonstrated that Infergen was slightly efficacious in reducing mortality and disease signs; however, it was not synergistic in its antiviral effects when combined with ribavirin. Ribavirin treatment alone increased mortality of infected hamsters. The reduced mortality correlated with reduced plasma viraemia. Since WNV-infected patients have already been treated with IFN and ribavirin and future clinical trials have been suggested, this first report of IFN alone or in combination with ribavirin in WNV-infected animal models might provide useful information for subsequent treatment of patients.
Morrey
John D
JD
Institute for Antiviral Research, Department of Animal, Dairy & Veterinary Sciences, Utah State University, Logan, UT, USA. jmorrey@cc.usu.edu
Day
Craig W
CW
Julander
Justin G
JG
Blatt
Lawrence M
LM
Smee
Donald F
DF
Sidwell
Robert W
RW
D000634:Aminoquinolines / Q000008:administration & dosage / Q000627:therapeutic use; D000818:Animals; D002478:Cells, Cultured; D006224:Cricetinae; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D006801:Humans; D000077271:Imiquimod; D007369:Interferon Inducers / Q000008:administration & dosage / Q000627:therapeutic use; D007370:Interferon Type I / Q000008:administration & dosage / Q000627:therapeutic use; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D007372:Interferons / Q000008:administration & dosage / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D009043:Motor Activity / Q000187:drug effects; D011070:Poly I-C / Q000008:administration & dosage / Q000627:therapeutic use; D011072:Poly U / Q000008:administration & dosage / Q000627:therapeutic use; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use; D015996:Survival Rate; D013997:Time Factors; D014901:West Nile Fever / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D014902:West Nile virus / Q000187:drug effects*
D000634:Aminoquinolines; D007369:Interferon Inducers; D007370:Interferon Type I; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011072:Poly U; D012254:Ribavirin; C050739:interferon alfacon-1; D007372:Interferons; C047490:poly(I).poly(c12,U); D011070:Poly I-C; D000077271:Imiquimod