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ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 38 Issue 7
Jul.  2022
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Article Contents

Research advances in the immune pathogenesis of hepatitis E virus infection

DOI: 10.3969/j.issn.1001-5256.2022.07.032
Research funding:

Scientific Research Fund of YouAn Medical Alliance for the Liver and Infectious Diseases (LM202019);

The Medical Treatment Combination Fund Project of Tianjin Xiqing Hospital (XQYYKLT202006)

More Information
  • Corresponding author: LI Hai, 15202265600@163.com (ORCID: 0000-0001-9563-6842)
  • Received Date: 2021-11-21
  • Accepted Date: 2022-01-27
  • Published Date: 2022-07-20
  • Hepatitis E is often acute and self-limited, but immunocompromised patients (such as solid organ transplantation recipients and patients with HIV infection or blood disease) may experience chronic infection. Immune response is the key factor for the outcome of hepatitis E virus (HEV) infection, which includes innate immunity and adaptive immunity. Various studies including cell culture, animal models, and clinical trials have helped to gain a deeper understanding of the immune pathogenesis of HEV, which provided ideas for new antiviral therapies for HEV and the development of effective vaccines. This article reviews the research on the immune pathogenesis of HEV infection in recent years and discusses the prospect of HEV prevention and treatment.

     

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  • [1]
    European Association for the Study of the Liver. EASL clinical practice guidelines on hepatitis E virus infection[J]. J Hepatol, 2018, 68(6): 1256-1271. DOI: 10.1016/j.jhep.2018.03.005.
    [2]
    LIN S, ZHANG YJ. Advances in hepatitis E virus biology and pathogenesis[J]. Viruses, 2021, 13(2): 267. DOI: 10.3390/v13020267.
    [3]
    PÉREZ-GRACIA MT, SUAY-GARCÍA B, MATEOS-LINDEMANN ML. Hepatitis E and pregnancy: current state[J]. Rev Med Virol, 2017, 27(3): e1929. DOI: 10.1002/rmv.1929.
    [4]
    THAKUR V, RATHO RK, KUMAR S, et al. Viral hepatitis E and chronicity: A growing public health concern[J]. Front Microbiol, 2020, 11: 577339. DOI: 10.3389/fmicb.2020.577339.
    [5]
    LI Y, PEPPELENBOSCH MP. Hepatitis E virus and neurological manifestations[J]. J Neurol Sci, 2021, 423: 117388. DOI: 10.1016/j.jns.2021.117388.
    [6]
    PISCHKE S, HARTL J, PAS SD, et al. Hepatitis E virus: Infection beyond the liver[J]. J Hepatol, 2017, 66(5): 1082-1095. DOI: 10.1016/j.jhep.2016.11.016.
    [7]
    LHOMME S, MIGUERES M, ABRAVANEL F, et al. Hepatitis E virus: How it escapes host innate immunity[J]. Vaccines (Basel), 2020, 8(3) : 422. DOI: 10.3390/vaccines8030422.
    [8]
    WU J, HUANG F, LING Z, et al. Altered faecal microbiota on the expression of Th cells responses in the exacerbation of patients with hepatitis E infection[J]. J Viral Hepat, 2020, 27(11): 1243-1252. DOI: 10.1111/jvh.13344.
    [9]
    NAIR VP, ANANG S, SUBRAMANI C, et al. Endoplasmic reticulum stress induced synthesis of a novel viral factor mediates efficient replication of genotype-1 hepatitis E virus[J]. PLoS Pathog, 2016, 12(4): e1005521. DOI: 10.1371/journal.ppat.1005521.
    [10]
    YAMADA K, TAKAHASHI M, HOSHINO Y, et al. ORF3 protein of hepatitis E virus is essential for virion release from infected cells[J]. J Gen Virol, 2009, 90(Pt 8): 1880-1891. DOI: 10.1099/vir.O.010561-0.
    [11]
    WU J, CHEN ZJ. Innate immune sensing and signaling of cytosolic nucleic acids[J]. Annu Rev Immunol, 2014, 32: 461-88. DOI: 10.1146/annurev-immunol-032713-120156.
    [12]
    TAKEUCHI O, AKIRA S. Innate immunity to virus infection[J]. Immunol Rev, 2009, 227(1): 75-86. DOI: 10.1111/j.1600-065X.2008.00737.x.
    [13]
    WU J, LING B, GUO N, et al. Immunological manifestations of hepatitis E-associated acute and chronic liver failure and its regulatory mechanisms[J]. Front Med (Lausanne), 2021, 8: 725993. DOI: 10.3389/fmed.2021.725993.
    [14]
    SRIVASTAVA R, AGGARWAL R, BHAGAT MR, et al. Alterations in natural killer cells and natural killer T cells during acute viral hepatitis E[J]. J Viral Hepat, 2008, 15(12): 910-916. DOI: 10.1111/j.1365-2893.2008.01036.x.
    [15]
    TAKEUCHI O, AKIRA S. Pattern recognition receptors and inflammation[J]. Cell, 2010, 140(6): 805-820. DOI: 10.1016/j.cell.2010.01.022.
    [16]
    JENSEN S, THOMSEN AR. Sensing of RNA viruses: a review of innate immune receptors involved in recognizing RNA virus invasion[J]. J Virol, 2012, 86(6): 2900-2910. DOI: 10.1128/JVI.05738-11.
    [17]
    DEVHARE PB, DESAI S, LOLE KS. Innate immune responses in human hepatocyte-derived cell lines alter genotype 1 hepatitis E virus replication efficiencies[J]. Sci Rep, 2016, 6: 26827. DOI: 10.1038/srep26827.
    [18]
    KAWAI T, AKIRA S. Toll-like receptors and their crosstalk with other innate receptors in infection and immunity[J]. Immunity, 2011, 34(5): 637-650. DOI: 10.1016/j.immuni.2011.05.006.
    [19]
    SYEDBASHA M, EGLI A. Interferon lambda: Modulating immunity in infectious diseases[J]. Front Immunol, 2017, 8: 119. DOI: 10.3389/fimmu.2017.00119.
    [20]
    NAN Y, WU C, ZHANG YJ. Interplay between janus kinase/signal transducer and activator of transcription signaling activated by type Ⅰ interferons and viral antagonism[J]. Front Immunol, 2017, 8: 1758. DOI: 10.3389/fimmu.2017.01758.
    [21]
    TODT D, FRANÇOIS C, ANGGAKUSUMA, et al. Antiviral activities of different interferon types and subtypes against hepatitis E virus replication[J]. Antimicrob Agents Chemother, 2016, 60(4): 2132-2139. DOI: 10.1128/AAC.02427-15.
    [22]
    SOORYANARAIN H, HEFFRON CL, MENG XJ. The U-rich untranslated region of the hepatitis E virus induces differential type Ⅰ and type Ⅲ interferon responses in a host cell-dependent manner[J]. mBio, 2020, 11(1) : e03103-19. DOI: 10.1128/mBio.03103-19.
    [23]
    MARION O, LHOMME S, NAYRAC M, et al. Hepatitis E virus replication in human intestinal cells[J]. Gut, 2020, 69(5): 901-910. DOI: 10.1136/gutjnl-2019-319004.
    [24]
    SCHNEIDER WM, CHEVILLOTTE MD, RICE CM. Interferon-stimulated genes: a complex web of host defenses[J]. Annu Rev Immunol, 2014, 32: 513-545. DOI: 10.1146/annurev-immunol-032713-120231.
    [25]
    MOAL V, TEXTORIS J, BEN AMARA A, et al. Chronic hepatitis E virus infection is specifically associated with an interferon-related transcriptional program[J]. J Infect Dis, 2013, 207(1): 125-132. DOI: 10.1093/infdis/jis632.
    [26]
    WANG W, YIN Y, XU L, et al. Unphosphorylated ISGF3 drives constitutive expression of interferon-stimulated genes to protect against viral infections[J]. Sci Signal, 2017, 10(476): eaah4248. DOI: 10.1126/scisignal.aah4248.
    [27]
    ZHOU X, XU L, WANG W, et al. Disparity of basal and therapeutically activated interferon signalling in constraining hepatitis E virus infection[J]. J Viral Hepat, 2016, 23(4): 294-304. DOI: 10.1111/jvh.12491.
    [28]
    XU L, WANG W, LI Y, et al. RIG-Ⅰ is a key antiviral interferon-stimulated gene against hepatitis E virus regardless of interferon production[J]. Hepatology, 2017, 65(6): 1823-1839. DOI: 10.1002/hep.29105.
    [29]
    XU L, ZHOU X, WANG W, et al. IFN regulatory factor 1 restricts hepatitis E virus replication by activating STAT1 to induce antiviral IFN-stimulated genes[J]. FASEB J, 2016, 30(10): 3352-3367. DOI: 10.1096/fj.201600356R.
    [30]
    LI Y, YU P, QU C, et al. MDA5 against enteric viruses through induction of interferon-like response partially via the JAK-STAT cascade[J]. Antiviral Res, 2020, 176: 104743. DOI: 10.1016/j.antiviral.2020.104743.
    [31]
    DEVHARE PB, CHATTERJEE SN, ARANKALLE VA, et al. Analysis of antiviral response in human epithelial cells infected with hepatitis E virus[J]. PLoS One, 2013, 8(5): e63793. DOI: 10.1371/journal.pone.0063793.
    [32]
    WANG W, XU L, BRANDSMA JH, et al. Convergent transcription of interferon-stimulated genes by TNF-α and IFN-α augments antiviral activity against HCV and HEV[J]. Sci Rep, 2016, 6: 25482. DOI: 10.1038/srep25482.
    [33]
    KUMAR A, DEVI SG, KAR P, et al. Association of cytokines in hepatitis E with pregnancy outcome[J]. Cytokine, 2014, 65(1): 95-104. DOI: 10.1016/j.cyto.2013.09.022.
    [34]
    XU J, WU F, TIAN D, et al. Open reading frame 3 of genotype 1 hepatitis E virus inhibits nuclear factor-kappa B signaling induced by tumor necrosis factor-α in human A549 lung epithelial cells[J]. PLoS One, 2014, 9(6): e100787. DOI: 10.1371/journal.pone.0100787.
    [35]
    LEI Q, LI L, ZHANG S, et al. HEV ORF3 downregulates TLR7 to inhibit the generation of type Ⅰ interferon via impairment of multiple signaling pathways[J]. Sci Rep, 2018, 8(1): 8585. DOI: 10.1038/s41598-018-26975-4.
    [36]
    LEI Q, LI L, HUANG W, et al. HEV ORF3 downregulatesCD14 and CD64 to impair macrophages phagocytosis through inhibiting JAK/STAT pathway[J]. J Med Virol, 2019, 91(6): 1112-1119. DOI: 10.1002/jmv.25400.
    [37]
    HE M, WANG M, HUANG Y, et al. The ORF3 protein of genotype 1 hepatitis E virus suppresses TLR3-induced NF-κB signaling via TRADD and RIP1[J]. Sci Rep, 2016, 6: 27597. DOI: 10.1038/srep27597.
    [38]
    TIAN Y, HUANG W, YANG J, et al. Systematic identification of hepatitis E virus ORF2 interactome reveals that TMEM134 engages in ORF2-mediated NF-κB pathway[J]. Virus Res, 2017, 228: 102-108. DOI: 10.1016/j.virusres.2016.11.027.
    [39]
    ZHU FC, HUANG SJ, WU T, et al. Epidemiology of zoonotic hepatitis E: a community-based surveillance study in a rural population in China[J]. PLoS One, 2014, 9(1): e87154. DOI: 10.1371/journal.pone.0087154.
    [40]
    KRAIN LJ, NELSON KE, LABRIQUE AB. Host immune status and response to hepatitis E virus infection[J]. Clin Microbiol Rev, 2014, 27(1): 139-165. DOI: 10.1128/CMR.00062-13.
    [41]
    HOOFNAGLE JH, NELSON KE, PURCELL RH. Hepatitis E[J]. N Engl J Med, 2012, 367(13): 1237-1244. DOI: 10.1056/NEJMra1204512.
    [42]
    KHUROO MS, KHUROO MS. Seroepidemiology of a second epidemic of hepatitis E in a population that had recorded first epidemic 30 years before and has been under surveillance since then[J]. Hepatol Int, 2010, 4(2): 494-499. DOI: 10.1007/s12072-009-9159-5.
    [43]
    TORRE P, AGLITTI A, MASARONE M, et al. Viral hepatitis: Milestones, unresolved issues, and future goals[J]. World J Gastroenterol, 2021, 27(28): 4603-4638. DOI: 10.3748/wjg.v27.i28.4603.
    [44]
    POSSAMAI LA, ANTONIADES CG, ANSTEE QM, et al. Role of monocytes and macrophages in experimental and human acute liver failure[J]. World J Gastroenterol, 2010, 16(15): 1811-1819. DOI: 10.3748/wjg.v16.i15.1811.
    [45]
    SHIN EC, SUNG PS, PARK SH. Immune responses and immunopathology in acute and chronic viral hepatitis[J]. Nat Rev Immunol, 2016, 16(8): 509-523. DOI: 10.1038/nri.2016.69.
    [46]
    HAKIM MS, SPAAN M, JANSSEN HL, et al. Inhibitory receptor molecules in chronic hepatitis B and C infections: novel targets for immunotherapy[J]. Rev Med Virol, 2014, 24(2): 125-138. DOI: 10.1002/rmv.1779.
    [47]
    CHEN S, ZHOU Z, WEI FX, et al. Modeling the long-term antibody response of a hepatitis E vaccine[J]. Vaccine, 2015, 33(33): 4124-4129. DOI: 10.1016/j.vaccine.2015.06.050.
    [48]
    SU YY, HUANG SJ, GUO M, et al. Persistence of antibodies acquired by natural hepatitis E virus infection and effects of vaccination[J]. Clin Microbiol Infect, 2017, 23(5): 336. e1-336. e4. DOI: 10.1016/j.cmi.2016.10.029
    [49]
    YU W, JI H, LONG F, et al. Inhibition of hepatitis E virus replication by zinc-finger antiviral Protein synergizes with IFN-β[J]. J Viral Hepat, 2021, 28(8): 1219-1229. DOI: 10.1111/jvh.13522.
    [50]
    SHRESTHA A, LAMA TK, GUPTA BP, et al. Hepatitis E virus outbreak in postearthquake Nepal: is a vaccine really needed[J]. J Viral Hepat, 2016, 23(6): 492. DOI: 10.1111/jvh.12505.
    [51]
    KUMAI T, FAN A, HARABUCHI Y, et al. Cancer immunotherapy: moving forward with peptide T cell vaccines[J]. Curr Opin Immunol, 2017, 47: 57-63. DOI: 10.1016/j.coi.2017.07.003.
    [52]
    MELSSEN M, SLINGLUFF CL Jr. Vaccines targeting helper T cells for cancer immunotherapy[J]. Curr Opin Immunol, 2017, 47: 85-92. DOI: 10.1016/j.coi.2017.07.004.
    [53]
    AL-AYOUBI J, BEHRENDT P, BREMER B, et al. Hepatitis E virus ORF 1 induces proliferative and functional T-cell responses in patients with ongoing and resolved hepatitis E[J]. Liver Int, 2018, 38(2): 266-277. DOI: 10.1111/liv.13521.
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