The hepatitis E virus (HEV) is the causative agent of acute and chronic hepatitis in humans. Related viruses have been found in several animal species. Reverse genetics systems (RGSs), which enable the generation of infectious virus from cloned cDNA by transfection of cultured cells or intrahepatic injection into laboratory animals, have been developed for HEV genotypes 1, 3, 4, 5 and 7 as well as for avian HEV and rat HEV. However, low virus recovery rates and slow replication in cell cultures are observed for most of the HEV types. Nevertheless, the RGSs enabled the site-directed mutagenesis of single nucleotides, deletion of genome fragments, insertion of sequence tags and a marker gene as well as the generation of chimeric viruses.
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