Recombinant Hepatitis E Virus Genomes Infectious for Primates: Importance of Capping and Discovery of a Cis-Reactive Element

Hepatitis E virus recombinant genomes transcribed in vitro from two cDNA clones differing by two nucleotides were infectious for chimpanzees. However, one cDNA clone encoded a virus that was attenuated for chimpanzees and unable to infect rhesus monkeys. The second cDNA clone encoded a virus that infected both chimpanzees and rhesus monkeys and caused acute hepatitis in both. One mutation differentiating the two clones identified a cis-reactive element that appeared to overlap the 3′ end of the capsid gene and part of the 3′ noncoding region. Capping of the RNA transcripts was essential for infectivity.