Hepatitis E viruses in humans and animals

2004 ◽  
Vol 5 (2) ◽  
pp. 145-156 ◽  
Author(s):  
S. Denise Goens ◽  
Michael L. Perdue

AbstractHepatitis E virus (HEV) is an emerging pathogen belonging to a newly recognized family of RNA viruses (Hepeviridae). HEV is an important enterically transmitted human pathogen with a worldwide distribution. It can cause sporadic cases as well as large epidemics of acute hepatitis. Epidemics are primarily waterborne in areas where water supplies are contaminated with HEV of human origin. There is increasing evidence, however, that many animal species are infected with an antigenically similar virus. A recently isolated swine virus is the best candidate for causing a zoonotic form of hepatitis E. The virus is serologically cross-reactive with human HEV and genetically very similar, and the human and swine strains seem to be cross-infective. Very recent evidence has also shown that swine HEV, and possibly a deer strain of HEV, can be transmitted to humans by consumption of contaminated meat. In this review, we discuss the prevalence, pathogenicity, diagnosis and control of human HEV, swine HEV, the related avian HEV and HEV in other hosts and potential reservoirs.

Author(s):  
X. J. Meng

Hepatitis E virus (HEV) is a small, non-enveloped, single-strand, positive-sense RNA virus of approximately 7.2 kb in size. HEV is classified in the family Hepeviridae consisting of four recognized major genotypes that infect humans and other animals. Genotypes 1 and 2 HEV are restricted to humans and often associated with large outbreaks and epidemics in developing countries with poor sanitation conditions, whereas genotypes 3 and 4 HEV infect humans, pigs and other animal species and are responsible for sporadic cases of hepatitis E in both developing and industrialized countries. The avian HEV associated with Hepatitis-Splenomegaly syndrome in chickens is genetically and antigenically related to mammalian HEV, and likely represents a new genus in the family. There exist three open reading frames in HEV genome: ORF1 encodes non-structural proteins, ORF2 encodes the capsid protein, and the ORF3 encodes a small phosphoprotein. ORF2 and ORF3 are translated from a single bicistronic mRNA, and overlap each other but neither overlaps ORF1. Due to the lack of an efficient cell culture system and a practical animal model for HEV, the mechanisms of HEV replication and pathogenesis are poorly understood. The recent identification and characterization of animal strains of HEV from pigs and chickens and the demonstrated ability of cross-species infection by these animal strains raise potential public health concerns for zoonotic HEV transmission. It has been shown that the genotypes 3 and 4 HEV strains from pigs can infect humans, and vice versa. Accumulating evidence indicated that hepatitis E is a zoonotic disease, and swine and perhaps other animal species are reservoirs for HEV. A vaccine against HEV is not yet available.


Animals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 277
Author(s):  
Eleonora Chelli ◽  
Elisabetta Suffredini ◽  
Paola De Santis ◽  
Dario De Medici ◽  
Santina Di Bella ◽  
...  

In Europe, foodborne transmission has been clearly associated to sporadic cases and small clusters of hepatitis E in humans linked to the consumption of contaminated pig liver sausages, raw venison, or undercooked wild boar meat. In Europe, zoonotic HEV-genotype 3 strains are widespread in pig farms but little information is available on the prevalence of HEV positive pigs at slaughterhouse. In the present study, the prevalence of HEV-RNA positive pigs was assessed on 585 animals from 4 abattoirs located across Italy. Twenty-one pigs (3.6%) tested positive for HEV in either feces or liver by real-time RT-PCR. In these 21 pigs, eight diaphragm muscles resulted positive for HEV-RNA. Among animals collected in one abattoir, 4 out of 91 plasma tested positive for HEV-RNA. ELISA tests for the detection of total antibodies against HEV showed a high seroprevalence (76.8%), confirming the frequent exposure of pigs to the virus. The phylogenetic analyses conducted on sequences of both ORF1 and ORF2 fragments, shows the circulation of HEV-3c and of a novel unclassified subtype. This study provides information on HEV occurrence in pigs at the slaughterhouse, confirming that muscles are rarely contaminated by HEV-RNA compared to liver, which is the most frequently positive for HEV.


2019 ◽  
Vol 93 (11) ◽  
Author(s):  
Huixia Li ◽  
Mengnan Fan ◽  
Baoyuan Liu ◽  
Pinpin Ji ◽  
Yiyang Chen ◽  
...  

ABSTRACT Avian hepatitis E virus (HEV) is the main causative agent of big liver and spleen disease in chickens. Due to the absence of a highly effective cell culture system, there are few reports about the interaction between avian HEV and host cells. In this study, organic anion-transporting polypeptide 1A2 (OATP1A2) from chicken liver cells was identified to interact with ap237, a truncated avian HEV capsid protein spanning amino acids 313 to 549, by a glutathione S-transferase (GST) pulldown assay. GST pulldown and indirect enzyme-linked immunosorbent assays (ELISAs) further confirmed that the extracellular domain of OATP1A2 directly binds with ap237. The expression levels of OATP1A2 in host cells are positively correlated with the amounts of ap237 attachment and virus infection. The distribution of OATP1A2 in different tissues is consistent with avian HEV infection in vivo. Finally, when the functions of OATP1A2 in cells are inhibited by its substrates or an inhibitor or blocked by ap237 or anti-OATP1A2 sera, attachment to and infection of host cells by avian HEV are significantly reduced. Collectively, these results displayed for the first time that OATP1A2 interacts with the avian HEV capsid protein and can influence viral infection in host cells. The present study provides new insight to understand the process of avian HEV infection of host cells. IMPORTANCE The process of viral infection is centered around the interaction between the virus and host cells. Due to the lack of a highly effective cell culture system in vitro, there is little understanding about the interaction between avian HEV and its host cells. In this study, a total of seven host proteins were screened in chicken liver cells by a truncated avian HEV capsid protein (ap237) in which the host protein OATP1A2 interacted with ap237. Overexpression of OATP1A2 in the cells can promote ap237 adsorption as well as avian HEV adsorption and infection of the cells. When the function of OATP1A2 in cells was inhibited by substrates or inhibitors, attachment and infection by avian HEV significantly decreased. The distribution of OATP1A2 in different chicken tissues corresponded with that in tissues during avian HEV infection. This is the first finding that OATP1A2 is involved in viral infection of host cells.


2005 ◽  
Vol 86 (9) ◽  
pp. 2585-2593 ◽  
Author(s):  
F. F. Huang ◽  
F. W. Pierson ◽  
T. E. Toth ◽  
X. J. Meng

Hepatitis E virus (HEV), the causative agent of hepatitis E, is an important human pathogen. Increasing evidence indicates that hepatitis E is a zoonosis. Avian HEV was recently discovered in chickens with hepatitis–splenomegaly syndrome in the USA. Like swine HEV from pigs, avian HEV is also genetically and antigenically related to human HEV. The objective of this study was to construct and characterize an infectious cDNA clone of avian HEV for future studies of HEV replication and pathogenesis. Three full-length cDNA clones of avian HEV, pT7-aHEV-5, pT7G-aHEV-10 and pT7G-aHEV-6, were constructed and their infectivity was tested by in vitro transfection of leghorn male hepatoma (LMH) chicken liver cells and by direct intrahepatic inoculation of specific-pathogen-free (SPF) chickens with capped RNA transcripts from the three clones. The results showed that the capped RNA transcripts from each of the three clones were replication competent when transfected into LMH cells as demonstrated by detection of viral antigens with avian HEV-specific antibodies. SPF chickens intrahepatically inoculated with the capped RNA transcripts from each of the three clones developed active avian HEV infections as evidenced by seroconversion to avian HEV antibodies, viraemia and faecal virus shedding. The infectivity was further confirmed by successful infection of naïve chickens with the viruses recovered from chickens inoculated with the RNA transcripts. The results indicated that all three cDNA clones of avian HEV are infectious both in vitro and in vivo. The availability of these infectious clones for a chicken strain of HEV now affords an opportunity to study the mechanisms of HEV cross-species infection and tissue tropism by constructing chimeric viruses among human, swine and avian HEVs.


2009 ◽  
Vol 7 (S1) ◽  
pp. S55-S63 ◽  
Author(s):  
Ronald Fayer ◽  
Palmer Orlandi ◽  
Michael L. Perdue

The hepatitis E virus and Cryptosporidium are waterborne pathogens, each consisting of distinct taxa, genotypes and isolates that infect humans, nonhuman animal species or both. Some are associated with disease, others are not. Factors contributing to disease are extremely complicated, possibly involving differences in one or more traits associated with an organism's taxon, genotype or isolate and its infectious dose, and age or condition, as well as the host's physiology and immune status. Potential virulence factors have not yet been identified for HEV. Putative virulence factors for Cryptosporidium might be found in recently recognized genes involved in processes such as excystation, adherence to host cells, invasion, intracellular maintenance and host cell destruction.


2011 ◽  
Vol 156 (8) ◽  
pp. 1451-1454 ◽  
Author(s):  
Santiago Mirazo ◽  
Natalia Ramos ◽  
José C. Russi ◽  
Gustavo Gagliano ◽  
Juan Arbiza

2015 ◽  
Vol 89 (10) ◽  
pp. 5491-5501 ◽  
Author(s):  
Xinjie Wang ◽  
Qin Zhao ◽  
Lu Dang ◽  
Yani Sun ◽  
Jiming Gao ◽  
...  

ABSTRACTAntisera raised against the avian hepatitis E virus (HEV) capsid protein are cross-reactive with human and swine HEV capsid proteins. In this study, two monoclonal antibodies (MAbs) against the avian HEV capsid protein, namely, 3E8 and 1B5, were shown to cross-react with the swine HEV capsid protein. The motifs involved in binding both MAbs were identified and characterized using phage display biopanning, peptide synthesis, and truncated or mutated protein expression, along with indirect enzyme-linked immunosorbent assay (ELISA) and Western blotting. The results showed that the I/VPHD motif is a necessary core sequence and that P and H are two key amino acids for recognition by MAb 3E8. The VKLYM/TS motif is the minimal amino acid sequence necessary for recognition by MAb 1B5. Cross-reactivity between the two epitopes and antibodies against avian, swine, and human HEVs in sera showed that both epitopes are common to avian, swine, and human HEVs. In addition, amino acid sequence alignment of the capsid proteins revealed that the key motifs of both novel epitopes are the same in HEVs from different animal species, predicting that they may be common to HEV isolates from boars, rabbits, rats, ferrets, mongooses, deer, and camels as well. Protein modeling analysis showed that both epitopes are at least partially exposed on the surface of the HEV capsid protein. Protective capacity analysis demonstrated that the two epitopes are nonprotective against avian HEV infection in chickens. Collectively, these studies characterize two novel linear B-cell epitopes common to avian, swine, and human HEVs, which furthers the understanding of HEV capsid protein antigenic structure.IMPORTANCEMore and more evidence indicates that the host range diversity of hepatitis E virus (HEV) is a global public health concern. A better understanding of the antigenic structure of the HEV capsid protein may improve disease diagnosis and prevention. In this study, binding site mapping and localization as well as the antigenic biology of two novel linear B-cell epitopes common to several different species of HEV were characterized. These findings partially reveal the antigenic structure of the HEV capsid protein and provide potential applications for the development of diagnostics and interventions for HEV infection.


2020 ◽  
Author(s):  
Hu Suk Lee ◽  
Duy Tung Dao ◽  
Vuong Nghia Bui ◽  
Anh Ngoc Bui ◽  
Duy Thanh Le ◽  
...  

Abstract Background: Hepatitis E virus (HEV) is one of the important zoonotic diseases with a worldwide distribution. The main objective of this study was to assess the sero-prevalence and phylogenetic analysis of HEV in Vietnam. Pig blood and fecal pooled samples were used to determine the prevalence of HEV. We evaluated the true prevalence (TP) of HEV from apparent prevalence (AP) by taking into account the sensitivity and specificity of diagnostic tests using a Bayesian approach. For phylogenetic analysis, the data compared with worldwide HEV reference strains illustrating all eight genotypes (G1-G8) which were identified in previous study.Results: A total of 475 sera and 250 fecal pooled samples were collected at slaughterhouses and pig farms from five provinces, in Viet Nam. Overall, the AP of HEV was 58.53% (95% CI: 53.95-62.70) while the TP was slightly higher (59.96%, 95% credible interval: 54.49-65.41). In terms of pooled samples, overall, the AP (13.38%, 95% credible interval: 9.89-17.30) of HEV was much higher than TP (6.80%, 95%CI: 4.01-10.66). One strain in Hanoi, two strains in Dak Lak, seven strains in An Giang, four strains in Son La and two strains in Nghe An were isolated. The phylogenetic tree demonstrated that 19 Vietnamese strains were clustered into HEV 3 and 4.Conclusions: This study provided evidence that HEV is circulating in domestic pigs in Vietnam. From a public health perspective, it is very important to raise public awareness for high-risk groups (e.g. slaughterhouse workers, pig traders, farmers and market sellers) who have more opportunities to come in contact with pig and contaminated meats.


2007 ◽  
Vol 88 (5) ◽  
pp. 1538-1544 ◽  
Author(s):  
P. Billam ◽  
Z. F. Sun ◽  
X.-J. Meng

Avian hepatitis E virus (HEV) was identified from chickens with hepatitis–splenomegaly syndrome. In this study, the complete genomic sequence of an apparently avirulent strain of avian HEV was determined to be 6649 nt in length, excluding the poly(A) tail, which is 5 nt shorter than the prototype avian HEV. Sequence analyses revealed that the ORF1 has 89.6 % nucleotide sequence identity, with numerous non-silent mutations and deletions, compared to the prototype strain. The ORF2 capsid gene showed 90.7 % sequence identity with six non-silent mutations, and ORF3 had four non-silent mutations with 97 % sequence identity. Overall, the apparently avirulent strain shares only 90.1 % nucleotide sequence identity with the prototype strain. The identification of significant non-silent mutations in the capsid gene and other regions suggests that these mutations may play a role in HEV attenuation. This is the first report of the full-length sequence of an apparently avirulent strain of HEV.


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