Animal Models of Chronic Hepatitis Delta Virus Infection Host–Virus Immunologic Interactions
Abstract
:1. Introduction
1.1. The Disease, Chronic HDV Infection
1.2. Main Characteristics of HDV
1.3. Virus Life Cycle
2. In Vitro HDV–Host Cell Interaction
3. Chronic HDV Infection Animal Models
3.1. “Natural” Animal Models
3.2. Mouse Models of HDV Replication
3.2.1. Injection of Mice with HDV Infectious Particles
3.2.2. HDV Transgenic Mice
3.2.3. Mice with “Humanized” Livers
- The availability of primary human hepatocytes is limited and they cannot be propagated in vitro, which limits the number of available animals.
- The susceptibility of primary human hepatocytes to HBV infection is highly variable and generally low, since these cells rapidly dedifferentiate, losing the expression of the NTCP receptor.
- The engraftment of human hepatocytes in the liver of mice requires the use of immunodeficient mice, thus the interaction of the immune system and the virus is lost and consequently experiments are restricted to studies analyzing virus host–cell interactions.
3.2.4. Development of Gene Delivery Vectors to Deliver HDV Genomes into Mice
4. Conclusions
Animal model | Main characteristics | References | |
---|---|---|---|
Natural animal model | chimpanzees | Chimpanzees can be efficiently infected by HDV, coinfection and superinfection experiments have been performed resulting in moderately severe and severe liver damage, respectively. | 79–81 |
woodchucks | Several laboratories have shown that woodchucks chronically infected with WHV can be infected by HDV and produce new HDV virions using WHV surface antigen to form the envelope. This animal model recapitulate many of the characterists of HDV infection in humans. | 76–78 | |
bats | HDV pseudotyped with surface proteins of bat hepadnavirus TBHBV is able to infect both primary hepatocytes, a pattern similar to the pattern observed with HDV-HBV | 83 | |
WT mice | wild-type & inmunodeficient mice | Mice injected with HDV virus obtained from woodchucks transiently infect and replicate in the liver | 44 |
HDV-transgenic mice | S-HDAg transgenic mice | S-HDAg is expressed in hepatocytes and localized in the nucleus. No liver injury was observed, thus S-HDAg protein is not responsible for HDV inducing liver damage. | 97 |
L-HDAg transgenic mice | L-HDAg is expressed in hepatocytes an localized in the nucleus. No liver injury was observed, thus L-HDAg protein is not responsible for HDV inducing liver damage. | 97 | |
HDV Ag x HBV sAg | The phenotype of these mice does not differ from the phenotype of the parents | 97 | |
HDV genome under the control of the Albumin promoter | HDV replication and S-HDAg expression was detected in several organs including the liver, muscle, and brain. However, no large HDV large antigen were detected in any tissue, indicating that there was no efficient HDV RNA editing. Furthermore, no liver pathology was observed. | 98 | |
Humanized mouse models | Fah-/-RAG-/-IL-2Rg-/- + human hepatocytes | Establishment of HDV infection was highly efficient in both HBV-infected and naïve chimeric mice, representing an interesting animal model to study HDV-human hepatocyte interaction and new antivirals. | 20,55,99 |
HDV-transfected mice | HDV plasmid hydrodynamic injection | In this animal model there is an increase of HDV genome and antigenome in the liver but only during the first two weeks after hydrodinamic injetion. There is no associated damage. Edition is observed in the liver. | 107 |
HDV-transfected mice | HDV plasmid intramuscular injection | Sustained RNA accumulation at least for 7 weeks. HDAg antibody generation | 106 |
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Aldabe, R.; Suárez-Amarán, L.; Usai, C.; González-Aseguinolaza, G. Animal Models of Chronic Hepatitis Delta Virus Infection Host–Virus Immunologic Interactions. Pathogens 2015, 4, 46-65. https://doi.org/10.3390/pathogens4010046
Aldabe R, Suárez-Amarán L, Usai C, González-Aseguinolaza G. Animal Models of Chronic Hepatitis Delta Virus Infection Host–Virus Immunologic Interactions. Pathogens. 2015; 4(1):46-65. https://doi.org/10.3390/pathogens4010046
Chicago/Turabian StyleAldabe, Rafael, Lester Suárez-Amarán, Carla Usai, and Gloria González-Aseguinolaza. 2015. "Animal Models of Chronic Hepatitis Delta Virus Infection Host–Virus Immunologic Interactions" Pathogens 4, no. 1: 46-65. https://doi.org/10.3390/pathogens4010046
APA StyleAldabe, R., Suárez-Amarán, L., Usai, C., & González-Aseguinolaza, G. (2015). Animal Models of Chronic Hepatitis Delta Virus Infection Host–Virus Immunologic Interactions. Pathogens, 4(1), 46-65. https://doi.org/10.3390/pathogens4010046