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      The Current Host Range of Hepatitis E Viruses

      review-article
      Viruses
      MDPI
      hepatitis E virus, HEV, host range, zoonosis, animals, virus transmission

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          Abstract

          Hepatitis E virus (HEV) is an emerging zoonotic pathogen transmitting both human to human via the fecal oral route and from animals to humans through feces, direct contact, and consumption of contaminated meat products. Understanding the host range of the virus is critical for determining where potential threats to human health may be emerging from and where potential reservoirs for viral persistence in the environment may be hiding. Initially thought to be a human specific disease endemic to developing countries, the identification of swine as a primary host for genotypes 3 and 4 HEV in industrialized countries has begun a long journey of discovering novel strains of HEV and their animal hosts. As we continue identifying new strains of HEV in disparate animal species, it is becoming abundantly clear that HEV has a broad host range and many of these HEV strains can cross between differing animal species. These cross-species transmitting strains pose many unique challenges to human health as they are often unrecognized as sources of viral transmission.

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          Most cited references136

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          Zoonotic hepatitis E: animal reservoirs and emerging risks

          Hepatitis E virus (HEV) is responsible for enterically-transmitted acute hepatitis in humans with two distinct epidemiological patterns. In endemic regions, large waterborne epidemics with thousands of people affected have been observed, and, in contrast, in non-endemic regions, sporadic cases have been described. Although contaminated water has been well documented as the source of infection in endemic regions, the modes of transmission in non-endemic regions are much less known. HEV is a single-strand, positive-sense RNA virus which is classified in the Hepeviridae family with at least four known main genotypes (1–4) of mammalian HEV and one avian HEV. HEV is unique among the known hepatitis viruses, in which it has an animal reservoir. In contrast to humans, swine and other mammalian animal species infected by HEV generally remain asymptomatic, whereas chickens infected by avian HEV may develop a disease known as Hepatitis-Splenomegaly syndrome. HEV genotypes 1 and 2 are found exclusively in humans while genotypes 3 and 4 are found both in humans and other mammals. Several lines of evidence indicate that, in some cases involving HEV genotypes 3 and 4, animal to human transmissions occur. Furthermore, individuals with direct contact with animals are at higher risk of HEV infection. Cross-species infections with HEV genotypes 3 and 4 have been demonstrated experimentally. However, not all sources of human infections have been identified thus far and in many cases, the origin of HEV infection in humans remains unknown.
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            Detection of a novel hepatitis E-like virus in faeces of wild rats using a nested broad-spectrum RT-PCR.

            Hepatitis E is a rare human disease in developed countries. It is caused by hepatitis E virus (HEV), which is probably transmitted zoonotically to humans from domestic pigs and wild boars. Multiple reports on the detection of HEV-specific antibodies in rats have suggested the presence of an HEV-related agent; however, infectious virus or a viral genome has not been demonstrated so far. Here, a nested broad-spectrum RT-PCR protocol was developed capable of detecting different HEV types including those derived from wild boar and chicken. Screening of 30 faecal samples from wild Norway rats (Rattus norvegicus) from Hamburg (Germany) resulted in the detection of two sequences with similarities to human, mammalian and avian HEV. Virus particles with a morphology reminiscent of HEV were demonstrated by immunoelectron microscopy in one of these samples and the virus was tentatively designated rat HEV. Genome fragments with sizes of 4019 and 1545 nt were amplified from two samples. Sequence comparison with human and avian strains revealed only 59.9 and 49.9 % sequence identity, respectively. Similarly, the deduced amino acid sequence for the complete capsid protein had 56.2 and 42.9 % identity with human and avian strains, respectively. Inoculation of the samples onto three different permanent rat liver cell lines did not result in detectable virus replication as assayed by RT-PCR with cells of the fifth virus passage. Further investigations are necessary to clarify the zoonotic potential of rat HEV and to assess its suitability to serve in a laboratory rat animal model for human hepatitis E.
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              Cross-species infections of cultured cells by hepatitis E virus and discovery of an infectious virus-host recombinant.

              The RNA virus, hepatitis E virus (HEV) is the most or second-most important cause of acute clinical hepatitis in adults throughout much of Asia, the Middle East, and Africa. In these regions it is an important cause of acute liver failure, especially in pregnant women who have a mortality rate of 20-30%. Until recently, hepatitis E was rarely identified in industrialized countries, but Hepatitis E now is reported increasingly throughout Western Europe, some Eastern European countries, and Japan. Most of these cases are caused by genotype 3, which is endemic in swine, and these cases are thought to be zoonotically acquired. However, transmission routes are not well understood. HEV that infect humans are divided into nonzoonotic (types 1, 2) and zoonotic (types 3, 4) genotypes. HEV cell culture is inefficient and limited, and thus far HEV has been cultured only in human cell lines. The HEV strain Kernow-C1 (genotype 3) isolated from a chronically infected patient was used to identify human, pig, and deer cell lines permissive for infection. Cross-species infections by genotypes 1 and 3 were studied with this set of cultures. Adaptation of the Kernow-C1 strain to growth in human hepatoma cells selected for a rare virus recombinant that contained an insertion of 174 ribonucleotides (58 amino acids) of a human ribosomal protein gene.
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                Author and article information

                Journal
                Viruses
                Viruses
                viruses
                Viruses
                MDPI
                1999-4915
                17 May 2019
                May 2019
                : 11
                : 5
                : 452
                Affiliations
                Food Animal Health Research Program, Department of Veterinary Preventive Medicine, The Ohio State University College of Veterinary Medicine, Wooster, OH 44691, USA; kenney.157@ 123456osu.edu
                Author information
                https://orcid.org/0000-0002-7449-2066
                Article
                viruses-11-00452
                10.3390/v11050452
                6563279
                31108942
                0740b530-b931-4649-b4ff-52664c93900f
                © 2019 by the author.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 24 April 2019
                : 14 May 2019
                Categories
                Review

                Microbiology & Virology
                hepatitis e virus,hev,host range,zoonosis,animals,virus transmission
                Microbiology & Virology
                hepatitis e virus, hev, host range, zoonosis, animals, virus transmission

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