Hepatitis
B virus (HBV) affects more than 257 million people globally,
resulting in progressively worsening liver disease, manifesting as
fibrosis, cirrhosis, and hepatocellular carcinoma. The exceptionally
narrow species tropism of HBV restricts its natural hosts to humans
and non-human primates, including chimpanzees, gorillas, gibbons,
and orangutans. The unavailability of completely immunocompetent
small-animal models has contributed to the lack of curative therapeutic
interventions. Even though surrogates allow the study of closely related
viruses, their host genetic backgrounds, immune responses, and molecular
virology differ from those of HBV. Various different models, based
on either pure murine or xenotransplantation systems, have been
introduced over the past years, often making the choice of the optimal
model for any given question challenging. Here, we offer a concise
review of in vivo model systems employed to study
HBV infection and steps in the HBV life cycle or pathogenesis.