TY - JOUR
T1 - Animal models for the study of human hepatitis B and D virus infection
T2 - New insights and progress
AU - Burwitz, Benjamin J.
AU - Zhou, Zhongmin
AU - Li, Wenhui
N1 - Publisher Copyright:
© 2020 Elsevier B.V.
PY - 2020/10
Y1 - 2020/10
N2 - Hepatitis B virus (HBV) is a member of the Hepadnaviridae family and infects hepatocytes, leading to liver pathology in acutely and chronically infected individuals. Co-infection with Hepatitis D virus (HDV), which requires the surface proteins of HBV to replicate, can exacerbate this disease progression. Thus, the >250 million people living with chronic HBV infection, including 13 million co-infected with HDV, would significantly benefit from an effective and affordable curative treatment. Animal models are crucial to the development of innovative disease therapies, a paradigm repeated again and again throughout the fields of immunology, neurology, reproduction, and development. Unfortunately, HBV has a highly-restricted species tropism, infecting limited species including humans, chimpanzees, and treeshrews. The first experimentally controlled studies of HBV infection were following inoculation of human volunteers in 1942, which identified the transmissibility of hepatitis through serum transfer and led to the hypothesis that the etiological agent was viral. Subsequent research in chimpanzees (Desmyter et al., 1971; Lichter, 1969) and later in other species, such as the treeshrews (Walter et al., 1996; Yan et al., 1996), further confirmed the viral origin of hepatitis B. Shortly thereafter, HBV-like viral infections were identified in woodchucks (Summers et al., 1978; Werner et al., 1979) and ducks, and much of our understanding of HBV replication can be attributed to these important models. However, with the exodus of chimpanzees from research and the limited reagents and historical data for treeshrews and other understudied species, there remains an urgent need to identify physiologically relevant models of chronic HBV infection. While large strides have been made in generating such models, particularly over the past two decades, there is still no available model that faithfully recapitulates the immunity and pathogenesis of HBV infection. Here, we discuss recent advancements in the generation of murine and non-human primate (NHP) models of HBV/HDV infection.
AB - Hepatitis B virus (HBV) is a member of the Hepadnaviridae family and infects hepatocytes, leading to liver pathology in acutely and chronically infected individuals. Co-infection with Hepatitis D virus (HDV), which requires the surface proteins of HBV to replicate, can exacerbate this disease progression. Thus, the >250 million people living with chronic HBV infection, including 13 million co-infected with HDV, would significantly benefit from an effective and affordable curative treatment. Animal models are crucial to the development of innovative disease therapies, a paradigm repeated again and again throughout the fields of immunology, neurology, reproduction, and development. Unfortunately, HBV has a highly-restricted species tropism, infecting limited species including humans, chimpanzees, and treeshrews. The first experimentally controlled studies of HBV infection were following inoculation of human volunteers in 1942, which identified the transmissibility of hepatitis through serum transfer and led to the hypothesis that the etiological agent was viral. Subsequent research in chimpanzees (Desmyter et al., 1971; Lichter, 1969) and later in other species, such as the treeshrews (Walter et al., 1996; Yan et al., 1996), further confirmed the viral origin of hepatitis B. Shortly thereafter, HBV-like viral infections were identified in woodchucks (Summers et al., 1978; Werner et al., 1979) and ducks, and much of our understanding of HBV replication can be attributed to these important models. However, with the exodus of chimpanzees from research and the limited reagents and historical data for treeshrews and other understudied species, there remains an urgent need to identify physiologically relevant models of chronic HBV infection. While large strides have been made in generating such models, particularly over the past two decades, there is still no available model that faithfully recapitulates the immunity and pathogenesis of HBV infection. Here, we discuss recent advancements in the generation of murine and non-human primate (NHP) models of HBV/HDV infection.
KW - Hepatitis B virus
KW - Hepatitis D virus
KW - Hepatocyte
KW - Mouse
KW - Non-human primate
KW - Sodium taurocholate co-transporting polypeptide
UR - http://www.scopus.com/inward/record.url?scp=85089485968&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85089485968&partnerID=8YFLogxK
U2 - 10.1016/j.antiviral.2020.104898
DO - 10.1016/j.antiviral.2020.104898
M3 - Review article
C2 - 32758525
AN - SCOPUS:85089485968
SN - 0166-3542
VL - 182
JO - Antiviral Research
JF - Antiviral Research
M1 - 104898
ER -