Analysis of Avian Hepatitis E Virus from Chickens, China

Zhao, Qin; Zhou, En‐Long; Dong, Shi; Qiu, Hong; Lu, Zengjun; Hu, Shou Bin; Zhao, Fei; Jiang, Shijin; Sun, Ya Ni

doi:10.3201/eid1609.100626

Cited by 74 publications

(75 citation statements)

References 12 publications

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“…To assess the protective capacity of the synthesized peptides containing the common epitopes, an animal immunization study was performed. Seven-week-old SPF chickens (n ϭ 30) were purchased from the Beijing Meiliyaweitong Experimental Animal Technology Company and confirmed to be negative for avian HEV RNA and antibodies by using RT-PCR and indirect ELISA (12,31). Chickens were divided into 5 groups (6/group) and housed at 2 chickens per cage.…”

Section: Methodsmentioning

confidence: 99%

“…The proteins encoded by ORF2 and ORF3 are produced from a bicistronic subgenomic (SG) mRNA, and the coding region of ORF2 overlaps ORF3, but neither overlaps ORF1 (8,9). To date, complete genomes of many animal HEVs, including HEVs from pigs (10), chickens (11,12), rabbits (13), deer (14), mongooses (15), rats (16,17), bats (18), and ferrets (19), have been characterized, and the host range and molecular diversity of HEVs are continually expanding (20). Swine HEV, the first identified animal strain of HEV, shares 80% to 90% nucleotide sequence identity with human HEV and can infect nonhuman primates (10).…”

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confidence: 99%

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Characterization of Two Novel Linear B-Cell Epitopes in the Capsid Protein of Avian Hepatitis E Virus (HEV) That Are Common to Avian, Swine, and Human HEVs

Wang

Zhao

et al. 2015

J Virol

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Antisera 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.H epatitis E is usually an acute and self-limiting disease in humans, is an epidemic in many developing countries in Asia and Africa (1-3), and occurs sporadically in some industrialized countries (4-6). The causative agent, hepatitis E virus (HEV), belongs to the Hepeviridae family and is a single-stranded, positivesense RNA virus. The viral genome contains three open reading frames (ORFs), ORF1, -2, and -3, encoding a viral nonstructural protein, a capsid protein, and a small multifunctional phosphoprotein (2, 7), respectively. The proteins encoded by ORF2 and ORF3 are produced from a bicistronic subgenomic (SG) mRNA, and the coding region of ORF2 overlaps ORF3, but neither overlaps ORF1 (8, 9). To date, complete genomes of m...

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

Characterization of Two Novel Linear B-Cell Epitopes in the Capsid Protein of Avian Hepatitis E Virus (HEV) That Are Common to Avian, Swine, and Human HEVs

Wang

Zhao

et al. 2015

J Virol

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“…and has the greatest genetic diversity, with 10 identified subgenotypes (3a to 3j). 7 Recently, new animal hepeviruses have been described in rats, 8 poultry, [9][10][11] and bats, 12 however they are phylogenetically divergent and likely define new genera within the Hepeviridae family.…”

Section: Introductionmentioning

confidence: 99%

High Prevalence of Hepatitis E in Humans and Pigs and Evidence of Genotype-3 Virus in Swine, Madagascar

Temmam¹,

Besnard²,

Andriamandimby³

et al. 2013

The American Society of Tropical Medicine and Hygiene

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Abstract. Hepatitis E virus (HEV) causes an orofecal disease transmitted through poor hygiene environments, contaminated food (mainly pork products), or by contacts with infected animals. Very little data are currently available regarding the disease in the Southwestern Indian Ocean Islands. We report the first sero-and viro-survey for HEV in human and swine in Madagascar. A seroprevalence rate of 14.1% (60 of 427) was measured in slaughterhouse workers. Seroprevalence to HEV in pigs was estimated to 71.2% (178 of 250), strongly suggesting the existence of a zoonotic cycle. Three out of 250 pig livers (1.2%) tested HEV RNA-positive by quantitative polymerase chain reaction. Phylogenetic analyses based on 1-kb sequences of the ORF 2-3 identified these viruses as HEV genotype 3. Sequences clustered in a distinct Malagasy sub-clade, possibly representative of a new sub-genotype, for which the date of emergence was estimated around 1989. Further studies are needed to confirm other transmission routes of HEV to humans, especially through non-zoonotic cycles.

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“…The status of avian HEV infection in chickens in Asia is largely unknown since there was only one report of avian HEV detection from China before the virus was identified recently in Korea and Taiwan (Hsu & Tsai, 2014; Kwon et al, 2012;Zhao et al, 2010). The Korean avian HEV belongs to genotype 1.…”

Section: Introductionmentioning

confidence: 99%

“…At least four different genotypes of avian HEV have been identified from chickens worldwide: genotype 1 from chickens in Australia, genotype 2 from chickens in the USA, genotype 3 from chickens in Europe and China, and genotype 4 from chickens in Hungary and Taiwan (Bányai et al, 2012;Bilic et al, 2009;Haqshenas et al, 2001;Hsu & Tsai, 2014;Huang et al, 2004;Marek et al, 2010;Zhao et al, 2010). The status of avian HEV infection in chickens in Asia is largely unknown since there was only one report of avian HEV detection from China before the virus was identified recently in Korea and Taiwan (Hsu & Tsai, 2014; Kwon et al, 2012;Zhao et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Construction of an infectious cDNA clone of genotype 1 avian hepatitis E virus: characterization of its pathogenicity in broiler breeders and demonstration of its utility in studying the role of the hypervariable region in virus replication

Park

Lee

Moon

et al. 2015

Journal of General Virology

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A full-length infectious cDNA clone of the genotype 1 Korean avian hepatitis E virus (avian HEV) (pT11-aHEV-K) was constructed and its infectivity and pathogenicity were investigated in leghorn male hepatoma (LMH) chicken cells and broiler breeders. We demonstrated that capped RNA transcripts from the pT11-aHEV-K clone were translation competent when transfected into LMH cells and infectious when injected intrahepatically into the livers of chickens. Gross and microscopic pathological lesions underpinned the avian HEV infection and helped characterize its pathogenicity in broiler breeder chickens. The avian HEV genome contains a hypervariable region (HVR) in ORF1. To demonstrate the utility of the avian HEV infectious clone, several mutants with various deletions in and beyond the known HVR were derived from the pT11-aHEV-K clone. The HVR-deletion mutants were replication competent in LMH cells, although the deletion mutants extending beyond the known HVR were non-viable. By using the pT11-aHEV-K infectious clone as the backbone, an avian HEV luciferase reporter replicon and HVR-deletion mutant replicons were also generated. The luciferase assay results of the reporter replicon and its mutants support the data obtained from the infectious clone and its derived mutants. To further determine the effect of HVR deletion on virus replication, the capped RNA transcripts from the wild-type pT11-aHEV-K clone and its mutants were injected intrahepatically into chickens. The HVR-deletion mutants that were translation competent in LMH cells displayed in chickens an attenuation phenotype of avian HEV infectivity, suggesting that the avian HEV HVR is important in modulating the virus infectivity and pathogenicity.

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Analysis of Avian Hepatitis E Virus from Chickens, China

Cited by 74 publications

References 12 publications

Characterization of Two Novel Linear B-Cell Epitopes in the Capsid Protein of Avian Hepatitis E Virus (HEV) That Are Common to Avian, Swine, and Human HEVs

Characterization of Two Novel Linear B-Cell Epitopes in the Capsid Protein of Avian Hepatitis E Virus (HEV) That Are Common to Avian, Swine, and Human HEVs

High Prevalence of Hepatitis E in Humans and Pigs and Evidence of Genotype-3 Virus in Swine, Madagascar

Construction of an infectious cDNA clone of genotype 1 avian hepatitis E virus: characterization of its pathogenicity in broiler breeders and demonstration of its utility in studying the role of the hypervariable region in virus replication

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