Pathogenesis of Hantaan Virus in Mice

The virulence of two virus clones (HV cl-1 and HV cl-2) of Hantaan virus, which were plaque-purified on Vero E6 cells, were compared in suckling mice infected by the intraperitoneal or intracerebral route. HV cl-1 increased the mortality of the mice whereas HV cl-2 did not. Furthermore, virus of high titre was isolated from various organs of mice infected with HV cl-1 and high titres were maintained, whereas after infection with HV cl-2, virus was isolated from various organs only in low titre and only temporarily. HV cl-1 strongly induced cell-to-cell fusion, but the cell fusion activity was at a minimum level in cells infected with HV cl-2. However these two clones induced similar titres of antibodies in mice. Cytotoxic T lymphocyte assays against macrophages infected with homologous and heterologous virus showed that cytotoxic T cell activity was induced in mice infected with HV cl-2, but suppressed in mice infected with HV cl-1. These results suggest that an alteration in the cell fusion function and the cytotoxic T cell activity are important in the pathogenesis of Hantaan virus infection in newborn mice.