Characterization of murine Caraparu Bunyavirus liver infection and immunomodulator-mediated antiviral protection.
A rapid, peripheral disease model utilizing the Bunyavirus, Caraparu, was established in mice for the evaluation of antiviral therapy with immunomodulators. 4-6-week-old B6C3F1 female mice, inoculated intraperitoneally with virus, developed coagulative liver necrosis and died between 4-6 days after infection. This Caraparu disease model was relatively resistant to treatment with immunomodulators, such as ABMP, Ampligen, alpha-interferon (IFN-alpha) or beta-interferon (IFN-beta). However, a significant increase in median survival time (MST) was consistently observed upon treatment with gamma-interferon (IFN-gamma). The nucleoside analog--ribavirin--was highly effective against Caraparu virus in repeated treatment schedules begun on either day -1, day 0, or day +1 of infection. Ribavirin gave little protection when initiation of treatment was delayed until day +2. However, combined treatment with IFN-gamma, starting on day 0 and ribavirin starting on day +2, significantly reduced mortality.
Brinton
M A
MA
Wistar Institute, Philadelphia, PA 19104.
Gavin
E I
EI
Lo
W K
WK
Pinto
A J
AJ
Morahan
P S
PS
D000276:Adjuvants, Immunologic / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002044:Bunyaviridae Infections / Q000188:drug therapy* / Q000382:microbiology; D005260:Female; D007371:Interferon-gamma / Q000494:pharmacology; D008099:Liver / Q000473:pathology; D008107:Liver Diseases / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D008854:Microscopy, Electron; D016851:Orthobunyavirus / Q000187:drug effects*; D011994:Recombinant Proteins; D012254:Ribavirin / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
D000276:Adjuvants, Immunologic; D000998:Antiviral Agents; D011994:Recombinant Proteins; D012254:Ribavirin; D007371:Interferon-gamma