Experimental animal models that have been used to study HEV include non-human primates, swine, rabbits, and human liver chimeric mice. Chimpanzees, rhesus monkeys, and Cynomolgus macaques were the earliest animal models in HEV research, and have been used to study HEV pathogenesis and vaccine efficacy. Swine, which are naturally infected with gts 3 and 4 of HEV and can transmit these strains to humans, have been used to determine the infectivity of gt 3 isolates, and to show extrahepatic replication sites of HEV. Recently, an iatrogenically immunosuppressed swine model was shown to support chronic infection with gt 3, and similarly, human liver chimeric mice can support chronic infection with gt1 and gt3 HEV. Gt, genotype.