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Hepatitis E virus: advances and challenges

Key Points

  • Hepatitis E virus (HEV) causes varying disease severity among patient subpopulations: it is self-limiting in most young adults, but causes 30% mortality in pregnant women and leads to chronicity in immunocompromised patients

  • HEV has a broad but poorly characterized host range, and in industrialized countries it is primarily transmitted zoonotically through the consumption of undercooked meat

  • A prophylactic vaccine against HEV exists but is currently only licensed in China

  • There are currently no direct-acting therapy available against HEV and no non-teratogenic treatment options for pregnant women, creating a need for the development of new therapeutics

  • The molecular biology of HEV remains incompletely understood

  • New model systems are emerging to study HEV, but more refined models are needed to gain insights in the interactions of HEV with its host, including mechanisms of HEV pathogenesis

Abstract

At least 20 million hepatitis E virus (HEV) infections occur annually, with >3 million symptomatic cases and 60,000 fatalities. Hepatitis E is generally self-limiting, with a case fatality rate of 0.5–3% in young adults. However, it can cause up to 30% mortality in pregnant women in the third trimester and can become chronic in immunocompromised individuals, such as those receiving organ transplants or chemotherapy and individuals with HIV infection. HEV is transmitted primarily via the faecal–oral route and was previously thought to be a public health concern only in developing countries. It is now also being frequently reported in industrialized countries, where it is transmitted zoonotically or through organ transplantation or blood transfusions. Although a vaccine for HEV has been developed, it is only licensed in China. Additionally, no effective, non-teratogenic and specific treatments against HEV infections are currently available. Although progress has been made in characterizing HEV biology, the scarcity of adequate experimental platforms has hampered further research. In this Review, we focus on providing an update on the HEV life cycle. We will further discuss existing cell culture and animal models and highlight platforms that have proven to be useful and/or are emerging for studying other hepatotropic (viral) pathogens.

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Figure 1: Host range of hepatitis E virus.
Figure 2: Genetic organization and translation of hepatitis E virus.
Figure 3: Life cycle of hepatitis E virus.
Figure 4: Towards more physiologically relevant 2D and 3D cell culture models for studying hepatitis E virus.
Figure 5: Experimental animal models to study hepatitis E virus Orthohepevirus A.

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Acknowledgements

The authors thank members of the Ploss laboratory for critical discussions of the manuscript. The work was supported in part by grants from Princeton University and an Investigator in Pathogenesis Award by the Burroughs Wellcome Fund (to A.P.). Q.D. is supported by a postdoctoral fellowship from the New Jersey Commission for Cancer Research. The authors apologize to all those whose work could not be cited due to space constraints.

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I.N. and A.P. wrote the article. All authors contributed equally to researching data for the article, discussion of content and reviewing/editing the manuscript before submission.

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Correspondence to Alexander Ploss.

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A.P. and Q.D. are inventors on a patent application defining a hepatitis E virus transcomplementation system for antiviral drug screening and the viroporin function of ORF3 as an antiviral drug target.

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Nimgaonkar, I., Ding, Q., Schwartz, R. et al. Hepatitis E virus: advances and challenges. Nat Rev Gastroenterol Hepatol 15, 96–110 (2018). https://doi.org/10.1038/nrgastro.2017.150

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