To HAV or not to HAV: Novel hepatitis A virus (HAV) infection in a chimeric mouse model

Abstract: Chimpanzees have been previously used to study HAV infection in vivo but they are expensive and difficult to maintain and thus, there is a need for a small animal model. Our aim is to test the susceptibility of the SCID-beige/Alb-uPA mice with chimeric human/mouse livers to HAV infection. Chimeric mice were IV inoculated with HAV and HAV produced fully infectious particles within the serum and feces, by one week post-infection. eHAV circulated the blood of infected chimeric mice consistent with human infections. Due to the lack of an adaptive immune system, HAV caused a persistent infection with a lack of inflammation within the liver. Pre-exposure to neutralizing antibody was fully protective while IFN treatment was able to suppress HAV infection. This study shows that the chimeric mice are permissive to HAV infection and represent a valuable small animal model for future studies.