The Hepatitis E Virus Open Reading Frame 2 Protein: Beyond Viral Capsid

Zhou, Zhen-Gong; Yin-qian, Xie; Wu, Chunyan; Nan, Yuchen

doi:10.3389/fmicb.2021.739124

Cited by 12 publications

(8 citation statements)

References 114 publications

(163 reference statements)

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“…[27] Thus far, three well-characterized open reading frames (ORF1-3) have been identified in the said genome. [28] ORF1 encodes non-structural proteins like helicase and RNA polymerase, while ORF2 encodes capsid proteins. The proteins encoded in ORF1 are translated from genomic RNA, while the proteins encoded in ORF2 and ORF3 are translated from a 2.2-kb-long subgenomic RNA strand.…”

Section: Discussionmentioning

confidence: 99%

Decreased Immunoreactivity of Hepatitis E Virus Antigen Following Treatment with Sakhalin Spruce (Picea glehnii) Essential Oil

Maeda

Horochi

Hasegawa

et al. 2023

Chemistry & Biodiversity

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The hepatitis E virus (HEV) causes a common infectious disease that infects pigs, wild boars, deer, and humans. In most cases, humans are infected by eating raw meat. Some essential oils have been reported to exhibit antiviral activities. In this study, in order to investigate the anti-HEV properties of essential oils, the immunoreactivities of HEV antigen proteins against the relevant antibodies were analyzed after the HEV antigens underwent treatment with various essential oils. The essential oils extracted from the tea tree, which was previously reported to exhibit antiviral activity, lavender, and lemon had strongly reduced activity. We found that treatment with the essential oil prepared from Sakhalin spruce was associated with the strongest reduction in immunoreactivity of HEV antigen protein(s) among the tested substances. The main volatile constituents of Sakhalin spruce essential oil were found to be bornyl acetate (32.30 %), α-pinene (16.66 %), camphene (11.14 %), camphor (5.52 %), β-phellandrene (9.09 %), borneol (4.77 %), and limonene (4.57 %). The anti-HEV properties of the various components of the essential oils were examined: treatment with bornyl acetate, the main component of Sakhalin spruce oil, α-pinene, the main component of tea tree oil, and limonene, the main component of lemon oil, resulted in a strong reduction in HEV antigen immunoreactivity. These results indicate that each main component of the essential oils plays an important role in the reduction of the immunoreactivity of HEV antigen protein(s); they also suggest that Sakhalin spruce essential oil exhibits anti-HEV activity. In a formulation with the potential to eliminate the infectivity of HEV in foodborne infections, this essential oil can be applied as an inactivating agent for meat processing and cooking utensils, such as knives and chopping boards.

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Section: Discussionmentioning

confidence: 99%

Decreased Immunoreactivity of Hepatitis E Virus Antigen Following Treatment with Sakhalin Spruce (Picea glehnii) Essential Oil

Maeda

Horochi

Hasegawa

et al. 2023

Chemistry & Biodiversity

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“…Unfortunately, until now, many preclinical trials have failed due to poor clinical management and insufficient or mixed data about the HEV RNA genome. The lack of knowledge about proteolytic processing and HEV capsid protein generation acts as a major obstacle in the development of a potent drug or vaccine [ 15 ]. Different studies have demonstrated the relation of HEV-ORF2 in different interspecies infection cases.…”

Section: Discussionmentioning

confidence: 99%

“…Although, the discovery of these forms of ORF2 are essential to understand the viral mode of action, the biological functions, catalytic and cleavage sites are still unknown [ 29 ]. In short, these reported changes have indicated the advanced protease processing and posttranslational modifications in the viral machinery which generate different ORF forms of HEV [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, this protein enhances the survival and stability of the virus in acidic and alkaline medium [ 13 , 14 ]. Different sequence and structural analyses have reported conserved binding motifs and β-barrel fold structures which contain polysaccharide binding sites among all HEV genomes which are involved in capsid disassembly and binding to host receptors [ 15 ]. This makes the HEV capsid protein a potential target to block viral entry into the host cells at an early stage of infection.…”

Section: Introductionmentioning

confidence: 99%

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Identification of Plant Peptides as Novel Inhibitors of Orthohepevirus A (HEV) Capsid Protein by Virtual Screening

et al. 2023

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Hepatitis E virus (HEV) is the notable causative agent of acute and chronic hepatic, renal, pancreatic, neurological, and hematopoietic blood cell infections with high risk in immunocompromised patients. Hepatic failure is mostly documented among adults, pregnant women, and patients with preexisting liver disease. HEV is a positive sense RNA virus of 7.2 kb genome size with typically three open reading frames (ORFs) which play essential roles in viral replication, genome assembly, and transcription. The mutational substitution in the viral RNA genome makes more it difficult to understand the actual relationship in the host–virus association. ORFs of HEV encode different structural and non-structural proteins and one of them is the capsid protein which is coded by ORF2. The capsid protein mediates the encapsulation of the viral genome as well as being involved in virion assembly. In the current study, the ligand-based docking approach was employed to inhibit the active amino acids of the viral capsid protein. Depending upon S-score, ADMET profiling, and drug scanning, the top ten tetrapeptides were selected as potential drug candidates with no toxicity counter to HEV receptor protein. The S-score or docking score is a mathematical function which predicts the binding affinities of docked complexes. The binding affinity of the predicted drug–target complexes helps in the selectivity of the desired compound as a potential drug. The best two selected peptides (i.e., TDGH with S-score of −8.5 and EGDE with S-score of −8.0) interacted with the active site amino acids of the capsid protein (i.e., Arg399, Gln420, and Asp444). The molecular dynamics simulations of RMSD trajectories of TDGH–capsid protein and EDGE–capsid protein have revealed that both docked complexes were structurally stable. The study revealed that these tetrapeptides would serve as strong potential inhibitors and a starting point for the development of new drug molecules against the HEV capsid protein. In future, in vivo studies are needed to explore selected peptides as potential drug candidates.

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“…Therefore, it is commonly used as antigen in several formats of immunoassays for detection of anti-HEV antibodies 21,51,52 . The glycosylated ORF2 (gORF2) is not part of the capsid and is released into plasma during viral replication 53 . The gORF2 can be present in sera for a longer time than the HEV genome and is a biomarker for active viral replication.…”

Section: Discussionmentioning

confidence: 99%

A Multispecies Competitive Nanobody-Based Elisa for the Detection of Antibodies Against Hepatitis E Virus

Arce

Pavan

Bok

et al. 2023

Preprint

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The hepatitis E virus (HEV) is an emergent zoonotic virus causing viral hepatitis worldwide. Clinically, hepatitis E is not easily distinguished from other types of acute viral hepatitis. There is a need for HEV diagnostic assays to detect and prevent interspecies transmission among susceptible populations. Nanobodies (Nbs) are expressed recombinantly in different systems, produced with high yields, and have superior physicochemical properties compared with conventional antibodies (Ab). Several Nbs against ORF2, the capsid protein and main antigen, were selected and produced in E. coli. Nb39 and Nb74 specifically recognized HEV ORF2 (genotypes 3 and 4). A competitive ELISA (cELISA) was developed and validated using a reference panel of human (n = 86) and swine sera (n = 116) tested in comparison with a commercial kit. The optimal cutoff values determined by ROC analysis were 69.16% (human) and 58.76% (swine); the sensitivity and specificity were high: 97.4% (IC95%; 86.5–99.5%) and 95.8% (IC95%; 86.0-98.8%) for human vs. 100% (IC95%: 93.5–100%) and 98.3% (IC95%: 91.0-99.7%) for swine. Further, the cELISA detected total anti-HEV antibodies in wild boar, deer, and mice. To our knowledge, this is the first report of production of Nbs against HEV-3 ORF2 for diagnostic purposes.

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The Hepatitis E Virus Open Reading Frame 2 Protein: Beyond Viral Capsid

Cited by 12 publications

References 114 publications

Decreased Immunoreactivity of Hepatitis E Virus Antigen Following Treatment with Sakhalin Spruce (Picea glehnii) Essential Oil

Decreased Immunoreactivity of Hepatitis E Virus Antigen Following Treatment with Sakhalin Spruce (Picea glehnii) Essential Oil

Identification of Plant Peptides as Novel Inhibitors of Orthohepevirus A (HEV) Capsid Protein by Virtual Screening

A Multispecies Competitive Nanobody-Based Elisa for the Detection of Antibodies Against Hepatitis E Virus

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