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
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.
Available from: Martin Eiden
- "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.
- "Inzwischen ist es auch möglich Hepatitis E Virus-spezifische T-Zellen bei Patienten mit frischer Infektion nachzuweisen und deren Aktivierung und Zytokin-Freisetzung mit dem Krankheitsverlauf zu korrelieren[9,41]. Inwieweit diese Erkenntnisse ggf. "
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ABSTRACT: The diagnosis of hepatitis E virus (HEV) infections has been recently substantially facilitated by the introduction of a whole range of new different virological assays. The increasing appearance of sporadic cases of acute hepatitis E in Germany directed the focus toward the zoonotic transmission route of the virus. The recognition of HEV genotypes differing in virulence and in pathogenic potential is not only relevant for epidemiology and the course of the disease, but also for the development and choice of diagnostic tools. A broad variety of enzymatic and protein-based assay formats detecting anti-HEV IgG or IgM antibodies directed against the different genotype variants of HEV is available (ELISA, LIA, Western blot); however, sensitivity and specificity of these assays differ notably. Today’s state-of-the art technology that permits fast and reliable assay-based confirmation of HEV infections is PCR. The newly developed commercially available PCR kits will detect all four human pathogenic HEV genotypes. Further subdivision and discrimination can be achieved by sequencing, although this approach is only reasonable in the setting of specific epidemiological demands. Detection of viral antigens, cell culture, and T-cell assays are of no practical importance in a routine diagnostic setting. New insight into the pathogenesis and its clinical relevance for defined groups of patients (immunosuppressed) as well as the implementation of specific antiviral and prophylactic therapies (vaccination) will further challenge the performance of existing assay formats and increase the technical demands for the diagnostic laboratory.
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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.
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