Hepatitis E Virus: from Innate Sensing to Adaptive Immune Responses

Overview

Journal Nat Rev Gastroenterol Hepatol

Specialty Gastroenterology

Date 2024 Jul 22

PMID 39039260

Authors

Yannick Bruggemann

Mara Klohn

Heiner Wedemeyer

Eike Steinmann

Affiliations

Soon will be listed here.

Abstract

Hepatitis E virus (HEV) infections are a major cause of acute viral hepatitis in humans worldwide. In immunocompetent individuals, the majority of HEV infections remain asymptomatic and lead to spontaneous clearance of the virus, and only a minority of individuals with infection (5-16%) experience symptoms of acute viral hepatitis. However, HEV infections can cause up to 30% mortality in pregnant women, become chronic in immunocompromised patients and cause extrahepatic manifestations. A growing body of evidence suggests that the host immune response to infection with different HEV genotypes is a critical determinant of distinct HEV infection outcomes. In this Review, we summarize key components of the innate and adaptive immune responses to HEV, including the underlying immunological mechanisms of HEV associated with acute and chronic liver failure and interactions between T cell and B cell responses. In addition, we discuss the current status of vaccines against HEV and raise outstanding questions regarding the immune responses induced by HEV and treatment of the disease, highlighting areas for future investigation.

References

Rein D, Stevens G, Theaker J, Wittenborn J, Wiersma S . The global burden of hepatitis E virus genotypes 1 and 2 in 2005. Hepatology. 2011; 55(4):988-97. DOI: 10.1002/hep.25505. View

Li P, Liu J, Li Y, Su J, Ma Z, Bramer W . The global epidemiology of hepatitis E virus infection: A systematic review and meta-analysis. Liver Int. 2020; 40(7):1516-1528. PMC: 7384095. DOI: 10.1111/liv.14468. View

Khuroo M . Study of an epidemic of non-A, non-B hepatitis. Possibility of another human hepatitis virus distinct from post-transfusion non-A, non-B type. Am J Med. 1980; 68(6):818-24. DOI: 10.1016/0002-9343(80)90200-4. View

Smith D, Izopet J, Nicot F, Simmonds P, Jameel S, Meng X . Update: proposed reference sequences for subtypes of hepatitis E virus (species ). J Gen Virol. 2020; 101(7):692-698. PMC: 7660235. DOI: 10.1099/jgv.0.001435. View

Nimgaonkar I, Ding Q, Schwartz R, Ploss A . Hepatitis E virus: advances and challenges. Nat Rev Gastroenterol Hepatol. 2017; 15(2):96-110. PMC: 11329273. DOI: 10.1038/nrgastro.2017.150. View

Gouttenoire J, Pollan A, Abrami L, Oechslin N, Mauron J, Matter M . Palmitoylation mediates membrane association of hepatitis E virus ORF3 protein and is required for infectious particle secretion. PLoS Pathog. 2018; 14(12):e1007471. PMC: 6307819. DOI: 10.1371/journal.ppat.1007471. View

Hartl J, Wehmeyer M, Pischke S . Acute Hepatitis E: Two Sides of the Same Coin. Viruses. 2016; 8(11). PMC: 5127013. DOI: 10.3390/v8110299. View

Navaneethan U, Al Mohajer M, Shata M . Hepatitis E and pregnancy: understanding the pathogenesis. Liver Int. 2008; 28(9):1190-9. PMC: 2575020. DOI: 10.1111/j.1478-3231.2008.01840.x. View

Kinast V, Klohn M, Nocke M, Todt D, Steinmann E . Hepatitis E virus species barriers: seeking viral and host determinants. Curr Opin Virol. 2022; 56:101274. DOI: 10.1016/j.coviro.2022.101274. View

10.

Chauhan A, Jameel S, Dilawari J, Chawla Y, Kaur U, Ganguly N . Hepatitis E virus transmission to a volunteer. Lancet. 1993; 341(8838):149-50. DOI: 10.1016/0140-6736(93)90008-5. View

11.

Huang S, Liu X, Zhang J, Ng M . Protective immunity against HEV. Curr Opin Virol. 2014; 5:1-6. DOI: 10.1016/j.coviro.2013.10.003. View

12.

Balayan M, Andjaparidze A, Savinskaya S, KETILADZE E, Braginsky D, SAVINOV A . Evidence for a virus in non-A, non-B hepatitis transmitted via the fecal-oral route. Intervirology. 1983; 20(1):23-31. DOI: 10.1159/000149370. View

13.

Walker C . Adaptive Immune Responses in Hepatitis A Virus and Hepatitis E Virus Infections. Cold Spring Harb Perspect Med. 2018; 9(9). PMC: 6531370. DOI: 10.1101/cshperspect.a033472. View

14.

Todt D, Friesland M, Moeller N, Praditya D, Kinast V, Bruggemann Y . Robust hepatitis E virus infection and transcriptional response in human hepatocytes. Proc Natl Acad Sci U S A. 2020; 117(3):1731-1741. PMC: 6983376. DOI: 10.1073/pnas.1912307117. View

15.

Krain L, Nelson K, Labrique A . Host immune status and response to hepatitis E virus infection. Clin Microbiol Rev. 2014; 27(1):139-65. PMC: 3910912. DOI: 10.1128/CMR.00062-13. View

16.

Kamar N, Selves J, Mansuy J, Ouezzani L, Peron J, Guitard J . Hepatitis E virus and chronic hepatitis in organ-transplant recipients. N Engl J Med. 2008; 358(8):811-7. DOI: 10.1056/NEJMoa0706992. View

17.

Abravanel F, Barrague H, Dorr G, Saune K, Peron J, Alric L . Conventional and innate lymphocytes response at the acute phase of HEV infection in transplanted patients. J Infect. 2016; 72(6):723-730. DOI: 10.1016/j.jinf.2016.02.016. View

18.

Kamar N, Pischke S . Acute and Persistent Hepatitis E Virus Genotype 3 and 4 Infection: Clinical Features, Pathogenesis, and Treatment. Cold Spring Harb Perspect Med. 2018; 9(7). PMC: 6601456. DOI: 10.1101/cshperspect.a031872. View

19.

Gotlieb N, Moradpour D, Shouval D . Hepatitis A and E - Differences and commonalities. J Hepatol. 2019; 72(3):578-580. DOI: 10.1016/j.jhep.2019.05.011. View

20.

Das A, Rivera-Serrano E, Yin X, Walker C, Feng Z, Lemon S . Cell entry and release of quasi-enveloped human hepatitis viruses. Nat Rev Microbiol. 2023; 21(9):573-589. PMC: 10127183. DOI: 10.1038/s41579-023-00889-z. View