Immunopathogenesis of Hepatitis E Virus Infection

Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.
Seminars in Liver Disease (Impact Factor: 4.95). 02/2013; 33(1):71-8. DOI: 10.1055/s-0033-1338118
Source: PubMed


The course of hepatitis E virus infection (HEV) can vary substantially between different individuals. Although most infections take a clinically silent asymptomatic course, a few patients may develop severe hepatitis that can progress to fulminant hepatic failure. In addition, cases of chronic hepatitis E have been described in immunosuppressed patients. The detailed mechanisms leading to different clinical outcomes of HEV infection are only partially understood. Both viral factors including the HEV genotype and the dose of the infectious inoculum, as well as host factors such as stage of liver disease, pregnancy or distinct genetic polymorphisms determine the course of HEV infection. Recent studies were able to associate T-cell responses, activation of the interferon system and viral evolution with severity or chronicity of hepatitis E. We here summarize the emerging data on the immunopathogenesis of HEV infection.

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    • "The reasons for the development of chronic HEV infections are unclear, but host factors like the age at exposure and the presence of co-infections have been discussed to modulate the clinical outcome of HEV infections (Casas et al., 2009; McCaustland et al., 2000). To date, chronic hepatitis E cases caused by HEV gt3 infections have been described in immunosuppressed patients only (Wedemeyer et al., 2013). "
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    ABSTRACT: Hepatitis E virus (HEV) causes acute hepatitis E in humans in developing countries, but sporadic and autochthonous cases do also occur in industrialized nations. In Europe, food-borne zoonotic transmission of genotype 3 (gt3) has been associated with the consumption of raw and undercooked products from domestic pig and wild boar. As shown recently, naturally acquired HEV gt3 replicates efficiently in experimentally infected wild boar and is transmissible from a wild boar to domestic pigs. Generally, following an acute infection swine suffer from a transient febrile illness and viremia in connection with fecal virus shedding. However, little is known about sub-acute or chronic HEV infections in swine, and how and where HEV survives the immune response. In this paper, we describe the incidental finding of a chronic HEVgt3 infection in two naturally infected European wild boar which were raised and housed at FLI over years. The wild boar displayed fecal HEV RNA excretion and viremia over nearly the whole observation period of more than five months. The animal had mounted a substantial antibody response, yet without initial clearance of the virus by the immune system. Further analysis indicated a subclinical course of HEV with no evidence of chronic hepatitis. Additionally, we could demonstrate that this chronic wild boar infection was still transmissible to domestic pigs, which were housed together with this animal. Sentinel pigs developed fecal virus shedding accompanied by seroconversion. Wild boar should therefore be considered as an important reservoir for transmission of HEV gt3 in Europe.
    Veterinary Microbiology 09/2015; DOI:10.1016/j.vetmic.2015.08.022 · 2.51 Impact Factor
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    ABSTRACT: Hepatitis E virus is a single, positive-sense, capped and poly A tailed RNA virus classified under the family Hepeviridae. Enteric transmission, acute self-limiting hepatitis, frequent epidemic and sporadic occurrence, high mortality in affected pregnants are hallmarks of hepatitis E infection. Lack of an efficient culture system and resulting reductionist approaches for the study of replication and pathogenesis of HEV made it to be a less understood agent. Early studies on animal models, sub-genomic expression of open reading frames (ORF) and infectious cDNA clones have helped in elucidating the genome organization, important stages in HEV replication and pathogenesis. The genome contains three ORF's and three untranslated regions (UTR). The 5′ distal ORF, ORF1 is translated by host ribosomes in a cap dependent manner to form the non-structural polyprotein including the viral replicase. HEV replicates via a negative-sense RNA intermediate which helps in the formation of the positive-sense genomic RNA and a single bi-cistronic sub-genomic RNA. The 3′ distal ORF's including the major structural protein pORF2 and the multifunctional host interacting protein pORF3 are translated from the sub-genomic RNA. Pathogenesis in HEV infections is not well articulated, and remains a concern due to the many aspects like host dependent and genotype specific variations. Animal HEV, zoonosis, chronicity in immunosuppressed patients, and rapid decompensation in affected chronic liver diseased patients warrants detailed investigation of the underlying pathogenesis. Recent advances about structure, entry, egress and functional characterization of ORF1 domains has furthered our understanding about HEV. This article is an effort to review our present understanding about molecular biology and pathogenesis of HEV.
    Journal of Clinical and Experimental Hepatology 06/2013; 3(2):114–124. DOI:10.1016/j.jceh.2013.05.001
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    ABSTRACT: Hepatitis E is an emerging disease with globally high incidence. In Indonesia, only few data on HEV infection are available. To assess molecular information on HEV infection in two communities with different customs and swine breeding conditions in Indonesia, serum samples from 137 swine farm workers, 100 blood donors and 100 swine (including 27 faecal) in Yogyakarta (Central of Java), along with 12 and 64 swine farm workers, 42 and 135 local residents also 89 and 119 swine serum samples in Tulungagung (East Java) and Mengwi (Bali), respectively from our previous study, were compared. Serological test of anti-HEV antibodies by ELISA, HEV-RNA detection by RT-PCR and phylogenetic analysis were performed. The total prevalence of anti-HEV antibodies in human was higher in Bali (11.6%) than in Java (5.1%); (P = 0.015). No significant differences of anti-HEV prevalence among swine farm workers and local residents in Java were shown. Swine HEV genotype 3 from Yogyakarta and genotype 4 from Tulungagung and Bali was somewhat different from other reports. We suggest other factors addition to close contact with swine might play an important role in HEV transmission of non-endemic/related custom groups. To the best of our knowledge, this is Indonesia's first report on swine HEV genotype 3.
    Microbiology and Immunology 07/2013; 57(10). DOI:10.1111/1348-0421.12083 · 1.24 Impact Factor
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