Etablierung und Charakterisierung von Mausmodellen für Lassa-Fieber

Abstract

In this study, transgenic HHD mice expressing human HLA A2.1 molecule instead of murine MHC-I molecules have been established as an animal model for Lassa virus (LASV) infection. It was found that HHD mice, in contrast to wild-type mice (C57BL/6), were susceptible for the LASV strain Ba366. LASV infection induced a severe illness with some fatalities. Genetic and functional T-cell depletions have shown that CD4 and CD8 positive T cells play a crucial role in pathogenesis in HHD mice. Immunological and histological findings indicate that the disease is associated with activation of macrophages, which is presumably T-cell dependent. Another murine animal model for LASV infection was established on the basis of interferon-alha/beta-receptor-deficient mice (A129). A129 mice were susceptible for all tested LASV strains and were affected by the infection. Biochemical, virological and histological analyzes showed similarities to Lassa fever disease. The suitability of A129 mouse model for antiviral compound screening was tested with ribavirin, the standard drug for human Lassa fever.