Experimental models of hepatitis B and C — new insights and progress

Abstract

Viral hepatitis is a major cause of morbidity and mortality, affecting hundreds of millions of people worldwide. Hepatitis-causing viruses initiate disease by establishing both acute and chronic infections, and several of these viruses are specifically associated with the development of hepatocellular carcinoma. Consequently, intense research efforts have been focusing on increasing our understanding of hepatitis virus biology and on improving antiviral therapy and vaccination strategies. Although valuable information on viral hepatitis emerged from careful epidemiological studies on sporadic outbreaks in humans, experimental models using cell culture, rodent and non-human primates were essential in advancing the field. Through the use of these experimental models, improvement in both the treatment and prevention of viral hepatitis has progressed rapidly; however, agents of viral hepatitis are still among the most common pathogens infecting humans. In this Review, we describe the important part that these experimental models have played in the study of viral hepatitis and led to monumental advances in our understanding and treatment of these pathogens. Ongoing developments in experimental models are also described.

Hepatitis B virus X protein: TRIMming antiviral defences in hepatocytes

“…Importantly, this study validated many of their findings using several distinct models of HBV infection including HepG2-NTCP cells, the HepaRG cell line, primary human hepatocytes and, finally, human liver tissues 13. Furthermore, this viral strategy to block immunity occurs at different levels immunity.…”

Hepatitis B Virus–Hepatocyte Interactions and Innate Immune Responses: Experimental Models and Molecular Mechanisms

“…The understanding of HBV-host interactions, including cellintrinsic innate immune responses after infection, has been hampered for many years by the paucity of robust and physiologic cell culture model systems 47,48 . This is specifically true for the study of HBV infection in hepatocyte models possessing functional host defense pathways that may also require the inclusion of nonparenchymal liver cells to be fully biologically relevant.…”

“…This is specifically true for the study of HBV infection in hepatocyte models possessing functional host defense pathways that may also require the inclusion of nonparenchymal liver cells to be fully biologically relevant. 27,48 As for most viruses, tumor-derived cells lines have been useful in increasing our understanding of HBV biology. Gene-editing approaches have been used to overexpress viral proteins and to generate cell lines that continuously express hepatitis viral genomes.…”

“…28 To investigate the pathways involved in sensing of HBV, including its DNA and associated RNA intermediates in human hepatocytes within minutes to hours after viral cell entry, several models have been described. 47,48 These include primary human hepatocytes (PHHs), which have functional intrinsic innate immune responses, and the HepaRG cell line, which is immortalized with some host defense pathways intact, as opposed to other transformed hepatoma cell lines. 50,51 Interestingly, owing to the differences in antiviral innate immunity within the HepG2 cell line when compared with Huh7 cells, this model has proven to be useful in the study of host defense pathways and to validate results obtained in PHHs.…”

“…19,53,54 These data suggest that results from immortalized and transformed cell lines should be validated in HepaRGs, PHHs, as well as in vivo models, if available, that may include humanized mice. 26,48,55 Unfortunately, even these models also have limitations. HepaRG cells are bipotent hepatic progenitor cells that can differentiate into both biliary and hepatocyte-like cells and can divide indefinitely.…”