The role of reverse genetics systems in studying viral hemorrhagic fevers
Hideki Ebihara1,5, Allison Groseth2,3, Gabriele Neumann4, Yoshihiro Kawaoka1,4,5, Heinz Feldmann2,3
1Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan 2National Microbiology Laboratory, National Laboratory for Zoonotic Diseases and Special Pathogens, Public Health Agency of
Summary Viral hemorrhagic fever (VHF) is an infectious syndrome in humansoften associated with high fatality rates. For most VHFsthere are no specific and effective therapies or vaccines availableand, in general, there is a lack of knowledge regarding the biologyand pathogenesis of the causative agents.Therefore, a moredetailed understanding of the molecular basis ofVHF pathogenesis,including the identification of viral virulence determinantsand host interactions and responses, will be important to enhance our ability to control VHF infections.The recently developed“reverse genetics systems” for severalVHF causing viruseshave allowed the generation of infectious viruses from clonedcDNA and thus, the generation of virus mutants. Here we reviewthe existing reverse genetics systems for VHF causing virusesand discuss their use in studying viral replication, pathogenesis,and the development of antivirals and vaccines.