scholarly journals Determination and analysis of the complete genomic sequence of avian hepatitis E virus (avian HEV) and attempts to infect rhesus monkeys with avian HEV

2004 ◽  
Vol 85 (6) ◽  
pp. 1609-1618 ◽  
Author(s):  
F. F. Huang ◽  
Z. F. Sun ◽  
S. U. Emerson ◽  
R. H. Purcell ◽  
H. L. Shivaprasad ◽  
...  
Keyword(s):  
Rhesus Monkeys ◽  
Hepatitis E Virus ◽  
Genomic Sequence ◽  
Hepatitis E ◽  
The United States ◽  
Open Reading Frames ◽  
Coding Region ◽  
Virus Shedding ◽  
Avian Hepatitis E Virus ◽  
Avian Hev

Avian hepatitis E virus (avian HEV), recently identified from a chicken with hepatitis–splenomegaly syndrome in the United States, is genetically and antigenically related to human and swine HEVs. In this study, sequencing of the genome was completed and an attempt was made to infect rhesus monkeys with avian HEV. The full-length genome of avian HEV, excluding the poly(A) tail, is 6654 bp in length, which is about 600 bp shorter than that of human and swine HEVs. Similar to human and swine HEV genomes, the avian HEV genome consists of a short 5′ non-coding region (NCR) followed by three partially overlapping open reading frames (ORFs) and a 3′NCR. Avian HEV shares about 50 % nucleotide sequence identity over the complete genome, 48–51 % identity in ORF1, 46–48 % identity in ORF2 and only 29–34 % identity in ORF3 with human and swine HEV strains. Significant genetic variations such as deletions and insertions, particularly in ORF1 of avian HEV, were observed. However, motifs in the putative functional domains of ORF1, such as the helicase and methyltransferase, were relatively conserved between avian HEV and mammalian HEVs, supporting the conclusion that avian HEV is a member of the genus Hepevirus. Phylogenetic analysis revealed that avian HEV represents a branch distinct from human and swine HEVs. Swine HEV infects non-human primates and possibly humans and thus may be zoonotic. An attempt was made to determine whether avian HEV also infects across species by experimentally inoculating two rhesus monkeys with avian HEV. Evidence of virus infection was not observed in the inoculated monkeys as there was no seroconversion, viraemia, faecal virus shedding or serum liver enzyme elevation. The results from this study confirmed that avian HEV is related to, but distinct from, human and swine HEVs; however, unlike swine HEV, avian HEV is probably not transmissible to non-human primates.

scholarly journals Analysis of the complete genomic sequence of an apparently avirulent strain of avian hepatitis E virus (avian HEV) identified major genetic differences compared with the prototype pathogenic strain of avian HEV

2007 ◽  
Vol 88 (5) ◽  
pp. 1538-1544 ◽  
Author(s):  
P. Billam ◽  
Z. F. Sun ◽  
X.-J. Meng
Keyword(s):  
Nucleotide Sequence Identity ◽  
Hepatitis E Virus ◽  
Genomic Sequence ◽  
Hepatitis E ◽  
Prototype Strain ◽  
Avirulent Strain ◽  
Sequence Identity ◽  
Avian Hepatitis E Virus ◽  
Avian Hev ◽  
Complete Genomic

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.

scholarly journals Identification of B-cell epitopes in the capsid protein of avian hepatitis E virus (avian HEV) that are common to human and swine HEVs or unique to avian HEV

2006 ◽  
Vol 87 (1) ◽  
pp. 217-223 ◽  
Author(s):  
H. Guo ◽  
E.-M. Zhou ◽  
Z. F. Sun ◽  
X.-J. Meng ◽  
P. G. Halbur
Keyword(s):  
B Cell ◽  
Hepatitis E Virus ◽  
Genomic Sequence ◽  
Rabbit Antiserum ◽  
Hepatitis E ◽  
Sequence Difference ◽  
B Cell Epitopes ◽  
Orf2 Protein ◽  
Avian Hepatitis E Virus ◽  
Avian Hev

Avian hepatitis E virus (avian HEV) was recently discovered in chickens from the USA that had hepatitis–splenomegaly (HS) syndrome. The complete genomic sequence of avian HEV shares about 50 % nucleotide sequence identity with those of human and swine HEVs. The open reading frame 2 (ORF2) protein of avian HEV has been shown to cross-react with human and swine HEV ORF2 proteins, but the B-cell epitopes in the avian HEV ORF2 protein have not been identified. Nine synthetic peptides from the predicted four antigenic domains of the avian HEV ORF2 protein were synthesized and corresponding rabbit anti-peptide antisera were generated. Using recombinant ORF2 proteins, convalescent pig and chicken antisera, peptides and anti-peptide rabbit sera, at least one epitope at the C terminus of domain II (possibly between aa 477–492) that is unique to avian HEV, one epitope in domain I (aa 389–410) that is common to avian, human and swine HEVs, and one or more epitopes in domain IV (aa 583–600) that are shared between avian and human HEVs were identified. Despite the sequence difference in ORF2 proteins between avian and mammalian HEVs and similar ORF2 sequence between human and swine HEV ORF2 proteins, rabbit antiserum against peptide 6 (aa 389–399) recognized only human HEV ORF2 protein, suggesting complexity of the ORF2 antigenicity. The identification of these B-cell epitopes in avian HEV ORF2 protein may be useful for vaccine design and may lead to future development of immunoassays for differential diagnosis of avian, swine and human HEV infections.

scholarly journals Egg whites from eggs of chickens infected experimentally with avian hepatitis E virus contain infectious virus, but evidence of complete vertical transmission is lacking

2007 ◽  
Vol 88 (5) ◽  
pp. 1532-1537 ◽  
Author(s):  
H. Guo ◽  
E. M. Zhou ◽  
Z. F. Sun ◽  
X.-J. Meng
Keyword(s):  
Vertical Transmission ◽  
Hepatitis E Virus ◽  
Infectious Virus ◽  
Hepatitis E ◽  
Egg White ◽  
Virus Shedding ◽  
Transmission Cycle ◽  
Chicken Egg ◽  
Avian Hepatitis E Virus ◽  
Avian Hev

Avian hepatitis E virus (HEV) is genetically and antigenically related to human HEV. Vertical transmission of HEV has been reported in humans, but not in other animals. In this study, we showed that avian HEV could be detected in chicken egg-white samples. Subsequently, avian HEV in egg white was found to be infectious, as evidenced by the appearance of viraemia, faecal virus shedding and seroconversion in chickens inoculated with avian HEV-positive egg white, but not in chickens inoculated with HEV-negative egg white. To further assess the possibility of vertical transmission of avian HEV, batches of embryonated eggs from infected hens were hatched, and hatched chicks were monitored for evidence of avian HEV infection. However, no virus was detected in samples collected from the hatched chicks throughout this study, suggesting that avian HEV could not complete the vertical transmission cycle. The possible implications of our findings are also discussed.

Rat Hepatitis E Virus Linked to Severe Acute Hepatitis in an Immunocompetent Patient

2019 ◽  
Vol 220 (6) ◽  
pp. 951-955 ◽  
Author(s):  
Anton Andonov ◽  
Mark Robbins ◽  
Jamie Borlang ◽  
Jingxin Cao ◽  
Todd Hatchette ◽  
...  
Keyword(s):  
Acute Hepatitis ◽  
Hepatitis E Virus ◽  
Genomic Sequence ◽  
Hepatitis E ◽  
The United States ◽  
Immunocompetent Patient ◽  
Health Concern ◽  
Animal Reservoir ◽  
Hepatitis Infection ◽  
Severe Acute Hepatitis

Abstract Hepatitis E virus (HEV) is a major public health concern in developing countries where the primary transmission is via contaminated water. Zoonotic HEV cases have been increasingly described in Europe, Japan, and the United States, with pigs representing the main animal reservoir of infection. We report an unusual acute hepatitis infection in a previously healthy man caused by a rat HEV with a considerably divergent genomic sequence compared with other rat HEV strains. It is possible that rat HEV is an underrecognized cause of hepatitis infection, and further studies are necessary to elucidate its potential risk and mode of transmission.

scholarly journals Chicken Organic Anion-Transporting Polypeptide 1A2, a Novel Avian Hepatitis E Virus (HEV) ORF2-Interacting Protein, Is Involved in Avian HEV Infection

2019 ◽  
Vol 93 (11) ◽  
Author(s):  
Huixia Li ◽  
Mengnan Fan ◽  
Baoyuan Liu ◽  
Pinpin Ji ◽  
Yiyang Chen ◽  
...  
Keyword(s):  
Viral Infection ◽  
Capsid Protein ◽  
Hepatitis E Virus ◽  
Organic Anion ◽  
Hepatitis E ◽  
Host Cells ◽  
Cell Culture System ◽  
Organic Anion Transporting Polypeptide ◽  
Avian Hepatitis E Virus ◽  
Avian Hev

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.

Hepatitis E virus

2011 ◽  
Author(s):  
X. J. Meng
Keyword(s):  
Hepatitis E Virus ◽  
Animal Species ◽  
Rna Virus ◽  
Hepatitis E ◽  
Open Reading Frames ◽  
Industrialized Countries ◽  
Efficient Cell Culture System ◽  
The Family ◽  
Avian Hev ◽  
Animal Strains

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.

scholarly journals Construction and characterization of infectious cDNA clones of a chicken strain of hepatitis E virus (HEV), avian HEV

2005 ◽  
Vol 86 (9) ◽  
pp. 2585-2593 ◽  
Author(s):  
F. F. Huang ◽  
F. W. Pierson ◽  
T. E. Toth ◽  
X. J. Meng
Keyword(s):  
Hepatitis E Virus ◽  
Hepatitis E ◽  
Cdna Clones ◽  
Virus Shedding ◽  
Rna Transcripts ◽  
Successful Infection ◽  
The Usa ◽  
Avian Hev

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.

scholarly journals 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

2015 ◽  
Vol 89 (10) ◽  
pp. 5491-5501 ◽  
Author(s):  
Xinjie Wang ◽  
Qin Zhao ◽  
Lu Dang ◽  
Yani Sun ◽  
Jiming Gao ◽  
...  
Keyword(s):  
Amino Acid ◽  
B Cell ◽  
Capsid Protein ◽  
Hepatitis E Virus ◽  
Hepatitis E ◽  
Antigenic Structure ◽  
B Cell Epitopes ◽  
Avian Hepatitis E Virus ◽  
Avian Hev ◽  
Linear B

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.

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