Table 1.
Cell culture models for HBV and HDV infection.
| Model | Entry | Replication | Secretion | de novo spread | Comments |
|---|---|---|---|---|---|
| PHH | HBV(+++) HDV(++) |
HBV(+++) HDV(+++) |
HBV(+)1 HDV(+)1,2 |
HBV(+)1 HDV(+)1,2 |
Pros: Gold standard in HBV/HDV infection; closest resemblance of hepatic metabolism and innate immune signaling Cons: Limited availability; high donor-to-doner variability |
| HepaRG | HBV(+) HDV(+) |
HBV(+++) HDV(+++) |
HBV(+) HDV(+)2 |
HBV(−) HDV(−) |
Pros: Physiologically close to PHH; competent innate immune signaling Cons: Requires sophisticated differentiation protocol; differentiates into biliary and hepatic cells; relatively low infection rate |
| HuH7 (transfection) | HBV(−) HDV(−) |
HBV(++) HDV(+++) |
HBV(++) HDV(+++)3 |
HBV(−) HDV(−) |
Pros: easy handling; widely available Cons: does not reflect authentic infection, especially the early stage of viral entry, internalization and trafficking in hepatocytes |
| HepAD38/HepG2.2.15 | HBV(−) | HBV(+++) | HBV(+++) | HBV(−) | Pros: easy handling; suitable for the production of HBV inoculate stock; feasible for drug screening that targets the late stage of HBV life cycle Cons: only partially resemble hepatocytes; does not reflect authentic HBV infection |
| HepG2-NTCP | HBV(+++) HDV(++) |
HBV(+++) HDV(++) |
HBV(+) HDV(++)2 |
HBV(−) HDV(−) |
Pros: easy handling; efficient infection rate for HBV and HDV; suitable for high throughput screening Cons: only partially resemble hepatocytes |
| HuH7-NTCP | HBV(+++) HDV(++) |
HBV(++) HDV(+++) |
HBV(+) HDV(++)2 |
HBV(−) HDV(−) |
Pros: easy handling; efficient infection rate for HDV; suitable for HDV-related high throughput screening Cons: only partially resemble hepatocytes; low infection rate for HBV; deficient in some aspects of innate immune signaling |
| HepG2-NTCPsec+ | HBV(+++) HDV(++) |
HBV(+++) HDV(++) |
HBV(++) HDV(++)2 |
HBV(++) HDV(++)2 |
Pros: supports the complete HBV life cycle, and long-term viral spread; supports the propagation of patient-derived HBV Cons: only partially resemble hepatocytes |
| HepNB2.7 | HDV(++) | HDV(+++) | HDV(+++) | HDV(+) | Pros: supports the complete HDV replication cycle, suitable for antiviral drug screening, especially for drugs interfering with late steps of the HDV life cycle, e.g., virion assembly and secretion; can be used to identify compounds that affect HBsAg secretion Cons: only partially resemble hepatocytes |
| HuH7-END | HDV(++) | HDV(+++) | HDV(+++) | HDV(+) | Pros: can be easily scaled up for preparation of large HDV virus stocks; suitable for screening of antiviral drugs targeting HDV replication; can be used to identify compounds that affect HBsAg secretion Cons: only partially resemble hepatocytes |
| Stem cell-derived hepatocytes | HBV(++) HDV(++) |
HBV(++) HDV(++) |
HBV(++) HDV(++)2 |
HBV(+) HDV(+)2 |
Pros: support long-term infection; physiologically close to PHH; support limited virus spread; with a better performance in 3D culture; serves as a potential personalized model Cons: requires elaborate differentiation protocol |
1
Long-term functional maintenance of PHH;
2
when co-infected with HBV; and
3
when co-transfected with a plasmid containing HBV genome or encoding HBsAg.
(−) no, (+) yes, low, (++) yes, moderate, (+++) yes, high.