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Review
. 2024 Sep 12;24(1):965.
doi: 10.1186/s12879-024-09870-4.

Hepatitis E virus immunosuppressed animal models

Kush Kumar Yadav  1   2 , Scott P Kenney  3   4
Affiliations
Review

Hepatitis E virus immunosuppressed animal models

Kush Kumar Yadav et al. BMC Infect Dis. .

Abstract

Hepatitis E virus (HEV) is an important emerging pathogen producing significant morbidity in immunosuppressed patients. HEV has been detrimental to solid organ transplant (SOT) patients, cancer patients, and HIV-positive patients, where chronic HEV infections occur. Blood-borne transfusions and multiple cases of chronic HEV infection in transplant patients have been reported in the past few decades, necessitating research on HEV pathogenesis using immunosuppressed animal models. Numerous animal species with unique naturally occurring HEV strains have been found, several of which have the potential to spread to humans and to serve as pathogenesis models. Host immunosuppression leads to viral persistence and chronic HEV infection allows for genetic adaptation to the human host creating new strains with worse disease outcomes. Procedures necessary for SOT often entail blood transfusions placing immunosuppressive patients into a "high risk group" for HEV infection. This scenario requires an appropriate immunosuppressive animal model to understand disease patterns in these patients. Hence, this article reviews the recent advances in the immunosuppressed animal models for chronic HEV infection with emphasis on pathogenesis, immune correlates, and the liver pathology associated with the chronic HEV infections.

Keywords: Animal; Chronic; Hepatitis; Humans; Immunosuppressed; Infection; Models.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Summary of immunosuppressed cynomolgus monkey model with intravenous (IV) HEV inoculation. HEV gt3 was used for the study. Interestingly, chronic hepatitis was evident but with the absence of fibrosis and cirrhosis in liver
Fig. 2
Fig. 2
Summary of immunosuppressed pig model with intravenous (IV) HEV inoculation. Th1, Th2 cytokines and CD4 + T cells were reduced during the acute phase, however, CD8 + T cells increased during the chronic phase of infection
Fig. 3
Fig. 3
Summary of immunosuppressed rabbit model with intravenous (IV) HEV inoculation. Chronic infection in rabbits with HEV gt3 leads to the development of fibrotic liver lesions. Cyclosporine A (CsA), rabbit (ra)
Fig. 4
Fig. 4
Summary of immunosuppressed mouse model with oral, intravenous (IV), intrasplenic (IS) and intraperitoneal (IP) HEV inoculation. HEV gt4 infection in Balb/c mice were more prominent to develop chronic HEV infection demonstrating necrotic and fibrotic liver lesions
Fig. 5
Fig. 5
Summary of immunosuppressive rat model with intravenous (IV) HEV inoculation. Chronically infected rats demonstrated the enhanced ALT liver enzyme level. Resolution of chronic infection was seen after the decrease in the immunosuppressive drugs which is the routine treatment regime in humans
Fig. 6
Fig. 6
Summary of immunosuppressed gerbil model with intravenous (IV) HEV inoculation. CD68 + macrophage was absent in the liver of chronically infected gerbils. Extrahepatic distribution of HEV was seen in the chronically infected gerbils
See this image and copyright information in PMC

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References

    1. Grange ZL, Goldstein T, Johnson CK, Anthony S, Gilardi K, Daszak P et al. Ranking the risk of animal-to-human spillover for newly discovered viruses. Proceedings of the National Academy of Sciences. 2021;118(15):e2002324118. - PMC - PubMed
    1. Lhomme S, Marion O, Abravanel F, Izopet J, Kamar N. Clinical manifestations, Pathogenesis and treatment of Hepatitis E Virus infections. J Clin Med. 2020;9(2). - PMC - PubMed
    1. Kamar N, Selves J, Mansuy JM, Ouezzani L, Péron JM, Guitard J, et al. Hepatitis E virus and chronic hepatitis in organ-transplant recipients. N Engl J Med. 2008;358(8):811–7. 10.1056/NEJMoa0706992 - DOI - PubMed
    1. Ollier L, Tieulie N, Sanderson F, Heudier P, Giordanengo V, Fuzibet JG, et al. Chronic hepatitis after hepatitis E virus infection in a patient with non-hodgkin lymphoma taking rituximab. Ann Intern Med. 2009;150(6):430–1. 10.7326/0003-4819-150-6-200903170-00026 - DOI - PubMed
    1. Dalton HR, Bendall RP, Keane FE, Tedder RS, Ijaz S. Persistent carriage of hepatitis E virus in patients with HIV infection. N Engl J Med. 2009;361(10):1025–7. 10.1056/NEJMc0903778 - DOI - PubMed

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