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Editor-in-Chief | Hepatitis E virus (HEV) is widely prevalent in the world, especially in East and South Asia, and also has sporadic epidemics in Japan, the United States, and Western Europe
.
HEV is usually acute or latent infection in healthy people, but in special groups such as pregnant women, organ transplant patients or patients with underlying liver disease, HEV infection can lead to severe hepatitis E, chronicity, extrahepatic damage and even death
.
Effective in vitro models are essential for studying the pathogenesis of hepatitis E, virus-host interactions and drug development
.
Currently, hepatoma cell lines are the most commonly used in vitro models of hepatitis E virus, but their characteristics are far from normal hepatocytes, and there are limitations in exploring host responses after infection and evaluating antiviral drugs
.
Organoids are generated from pluripotent stem cells or organ progenitor cells that differentiate and spontaneously form structures highly similar to the source tissue or organ in vivo, while maintaining the structure, composition, diversity and function of the source tissue/organ cell type has unique advantages
.
Recently, Pan Qiuwei's research group from Erasmus University Medical Center in the Netherlands and Wang Yijin's team from Southern University of Science and Technology published a research paper entitled Recapitulating hepatitis E virus–host interactions and facilitating antiviral drug discovery in human liver–derived organoids in Science Advances
.
This study successfully established an in vitro replication and infection model of hepatitis E virus using human-derived liver organoids.
The model supports the entire life cycle of hepatitis E virus infection and is suitable for studying virus-host interactions and antiviral drug screening.
.
In the previous study and in this study, the research group found that hepatocytes and cholangiocytes in the liver of patients with hepatitis E can be directly infected with hepatitis E virus
.
Stem cell populations in liver tissue are mainly located in the biliary compartment, which can be cultured in vitro into organoids with a cholangiocyte phenotype, and can be differentiated into hepatocytes under specific culture conditions
.
In this study, normal human liver tissue was used to obtain 3D cultured organoids, and the hepatitis E virus RNA obtained by the reverse genetic system was introduced into organoid cells or virus particles by electroporation to directly infect the organoids, confirming that the differentiated and undifferentiated 3D liver Organoids were effective in supporting hepatitis E virus replication and infection (Figure 1)
.
Figure 1.
3D cultured human liver organoids can effectively support hepatitis E virus replication and infection in both differentiated (right) and undifferentiated (left) states.
The researchers then used the Transwell culture system to transform 3D liver organoids into 2D monolayer
.
Both differentiated and undifferentiated 2D liver organoids can also effectively support hepatitis E virus replication and infection, and it was further found that virus particles in this system are more likely to be released from the apical end of the cell rather than from the basal end to the supernatant, so this model must be Extensively mimics the way the human liver detoxifies (Figure 2)
.
Figure 2.
Human-derived liver organoids cultured in 2D efficiently support hepatitis E virus replication and infection and its viral release pattern
.
In addition, this study explored the interaction between hepatitis E virus and the host through transcriptomics and tRNAomics, and verified the activation of the interferon pathway and its antiviral effect
.
Finally, using a 3D organoid-based hepatitis E virus replication model, it was found that homoharringtonine (Homoharringtonine) has a high anti-hepatitis E virus effect by screening a broad-spectrum antiviral drug library
.
At the same concentration, it is stronger than the clinically used anti-hepatitis E drug Ribavirin (Figure 3)
.
Homoharringtonine is mainly used to treat leukemia, and its anti-hepatitis E effect needs to be verified by later in vivo experiments
.
In conclusion, this study successfully established a novel in vitro model of hepatitis E virus based on human liver organoids
.
This system will greatly promote the research on the interaction between hepatitis E virus and the host and the screening of antiviral drugs
.
However, this model is currently mainly applicable to genotype 3 hepatitis E virus, and the models of other genotypes need to be further explored and optimized
.
Doctoral student Li Pengfei is the first author of the paper, and Dr.
Pan Qiuwei and Associate Professor Wang Yijin are the co-corresponding authors
.
Link to the original text: https:// Publisher: 11 Reprint Notice [Non-original article] The copyright of this article belongs to the author of the article, and personal sharing is welcome.
Reprinting is prohibited without permission.
The author has all legal rights, and violators will be prosecuted
.
.
HEV is usually acute or latent infection in healthy people, but in special groups such as pregnant women, organ transplant patients or patients with underlying liver disease, HEV infection can lead to severe hepatitis E, chronicity, extrahepatic damage and even death
.
Effective in vitro models are essential for studying the pathogenesis of hepatitis E, virus-host interactions and drug development
.
Currently, hepatoma cell lines are the most commonly used in vitro models of hepatitis E virus, but their characteristics are far from normal hepatocytes, and there are limitations in exploring host responses after infection and evaluating antiviral drugs
.
Organoids are generated from pluripotent stem cells or organ progenitor cells that differentiate and spontaneously form structures highly similar to the source tissue or organ in vivo, while maintaining the structure, composition, diversity and function of the source tissue/organ cell type has unique advantages
.
Recently, Pan Qiuwei's research group from Erasmus University Medical Center in the Netherlands and Wang Yijin's team from Southern University of Science and Technology published a research paper entitled Recapitulating hepatitis E virus–host interactions and facilitating antiviral drug discovery in human liver–derived organoids in Science Advances
.
This study successfully established an in vitro replication and infection model of hepatitis E virus using human-derived liver organoids.
The model supports the entire life cycle of hepatitis E virus infection and is suitable for studying virus-host interactions and antiviral drug screening.
.
In the previous study and in this study, the research group found that hepatocytes and cholangiocytes in the liver of patients with hepatitis E can be directly infected with hepatitis E virus
.
Stem cell populations in liver tissue are mainly located in the biliary compartment, which can be cultured in vitro into organoids with a cholangiocyte phenotype, and can be differentiated into hepatocytes under specific culture conditions
.
In this study, normal human liver tissue was used to obtain 3D cultured organoids, and the hepatitis E virus RNA obtained by the reverse genetic system was introduced into organoid cells or virus particles by electroporation to directly infect the organoids, confirming that the differentiated and undifferentiated 3D liver Organoids were effective in supporting hepatitis E virus replication and infection (Figure 1)
.
Figure 1.
3D cultured human liver organoids can effectively support hepatitis E virus replication and infection in both differentiated (right) and undifferentiated (left) states.
The researchers then used the Transwell culture system to transform 3D liver organoids into 2D monolayer
.
Both differentiated and undifferentiated 2D liver organoids can also effectively support hepatitis E virus replication and infection, and it was further found that virus particles in this system are more likely to be released from the apical end of the cell rather than from the basal end to the supernatant, so this model must be Extensively mimics the way the human liver detoxifies (Figure 2)
.
Figure 2.
Human-derived liver organoids cultured in 2D efficiently support hepatitis E virus replication and infection and its viral release pattern
.
In addition, this study explored the interaction between hepatitis E virus and the host through transcriptomics and tRNAomics, and verified the activation of the interferon pathway and its antiviral effect
.
Finally, using a 3D organoid-based hepatitis E virus replication model, it was found that homoharringtonine (Homoharringtonine) has a high anti-hepatitis E virus effect by screening a broad-spectrum antiviral drug library
.
At the same concentration, it is stronger than the clinically used anti-hepatitis E drug Ribavirin (Figure 3)
.
Homoharringtonine is mainly used to treat leukemia, and its anti-hepatitis E effect needs to be verified by later in vivo experiments
.
In conclusion, this study successfully established a novel in vitro model of hepatitis E virus based on human liver organoids
.
This system will greatly promote the research on the interaction between hepatitis E virus and the host and the screening of antiviral drugs
.
However, this model is currently mainly applicable to genotype 3 hepatitis E virus, and the models of other genotypes need to be further explored and optimized
.
Doctoral student Li Pengfei is the first author of the paper, and Dr.
Pan Qiuwei and Associate Professor Wang Yijin are the co-corresponding authors
.
Link to the original text: https:// Publisher: 11 Reprint Notice [Non-original article] The copyright of this article belongs to the author of the article, and personal sharing is welcome.
Reprinting is prohibited without permission.
The author has all legal rights, and violators will be prosecuted
.