RIBAVIRIN EFFICACY IN AN IN-VIVO MODEL OF CRIMEAN-CONGO HEMORRHAGIC-FEVER VIRUS (CCHF) INFECTION

After intraperitoneal (i.p.) infection of infant mice with CCHF virus, virus titers in liver remained significantly higher than in other org ans except blood (serum). Within the liver, virus antigen was first fo und by immunofluorescence (IFA) in Kupffer cells followed by more exte nsive hepatic spread. Later, virus was found in other organs including brain and heart. Ribavirin treatment significantly reduced infant mou se mortality and extended the geometric mean time to death. Ribavirin treatment reduced CCHF virus growth in liver and significantly decreas ed, but did not prevent, viremia. Despite a substantial viremia, infec tion of other organs including brain and heart was not detected in rib avirin-treated mice. A hepatotropic virus subpopulation with less neur ovirulence than the parent was isolated from liver of ribavirin-treate d mice (single dose, 100 mg/kg). After serial passage in placebo-treat ed mice, the exclusive hepatotropism was lost.