scholarly journals Progress in the Production of Virus-Like Particles for Vaccination against Hepatitis E Virus

Viruses ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 826
Author(s):  
Milena Mazalovska ◽  
J. Calvin Kouokam
Keyword(s):  
Viral Hepatitis ◽  
Hepatitis E Virus ◽  
Vaccine Development ◽  
Genetic Material ◽  
Hepatitis E ◽  
Open Reading Frames ◽  
Virus Like Particles ◽  
Ssrna Virus ◽  
Potential Vaccine ◽  
Reading Frames

Hepatitis E virus (HEV), a pathogen that causes acute viral hepatitis, is a small icosahedral, quasi-enveloped, positive ssRNA virus. Its genome has three open reading frames (ORFs), with ORF1 and ORF3 encoding for nonstructural and regulatory proteins, respectively, while ORF2 is translated into the structural, capsid protein. ORF2 is most widely used for vaccine development in viral hepatitis. Hepatitis E virus-like particles (VLPs) are potential vaccine candidates against HEV infection. VLPs are composed of capsid subunits mimicking the natural configuration of the native virus but lack the genetic material needed for replication. As a result, VLPs are unable to replicate and cause disease, constituting safe vaccine platforms. Currently, the recombinant VLP-based vaccine Hecolin® against HEV is only licensed in China. Herein, systematic information about the expression of various HEV ORF2 sequences and their ability to form VLPs in different systems is provided.

scholarly journals Mapping of linear B cell epitopes on open reading frames 2- and 3-encoded proteins of hepatitis E virus using synthetic peptides

1993 ◽  
Vol 109 (2-3) ◽  
pp. 251-255 ◽  
Author(s):  
Pierre Coursaget ◽  
Yves Buisson ◽  
Nathalie Depril ◽  
Pierre Cann ◽  
Martine Chabaud ◽  
...  
Keyword(s):  
B Cell ◽  
Synthetic Peptides ◽  
Hepatitis E Virus ◽  
Hepatitis E ◽  
Open Reading Frames ◽  
B Cell Epitopes ◽  
Encoded Proteins ◽  
Reading Frames ◽  
Linear B

An analysis of two open reading frames (ORF3 and ORF4) of rat hepatitis E virus genome using its infectious cDNA clones with mutations in ORF3 or ORF4

2018 ◽  
Vol 249 ◽  
pp. 16-30 ◽  
Author(s):  
Tanggis ◽  
Tominari Kobayashi ◽  
Masaharu Takahashi ◽  
Suljid Jirintai ◽  
Tsutomu Nishizawa ◽  
...  
Keyword(s):  
Hepatitis E Virus ◽  
Hepatitis E ◽  
Virus Genome ◽  
Open Reading Frames ◽  
Cdna Clones ◽  
Reading Frames

The effects of synonymous codon usages on genotypic formation of open reading frames in hepatitis E virus

2020 ◽  
Vol 85 ◽  
pp. 104450
Author(s):  
Jing Sun ◽  
Caiqin Ren ◽  
Ying Huang ◽  
Wenhan Chao ◽  
Fuqiang Xie
Keyword(s):  
Hepatitis E Virus ◽  
Synonymous Codon ◽  
Hepatitis E ◽  
Open Reading Frames ◽  
Reading Frames

scholarly journals Immunogenicity and Antigenicity of Rabbit Hepatitis E Virus-Like Particles Produced by Recombinant Baculoviruses

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1573
Author(s):  
Huimin Bai ◽  
Michiyo Kataoka ◽  
Yasushi Ami ◽  
Yuriko Suzaki ◽  
Naokazu Takeda ◽  
...  
Keyword(s):  
Hepatitis E Virus ◽  
Vaccine Development ◽  
Ex Vivo ◽  
High Titer ◽  
Hepatitis E ◽  
Cross Reactivity ◽  
Recombinant Baculoviruses ◽  
Genotype 3 ◽  
Human Carcinoma ◽  
Virus Like Particles

Rabbit hepatitis E virus (HEV) is a novel HEV belonging to genotype 3 (HEV-3) in the Orthohepevirus A species of the genus Hepevirus, family Hepeviridae. Rabbit HEV was originally isolated from rabbits and found to cause zoonotic infection. Although rabbit HEV can be successfully grown in culture with several cell lines, including the human carcinoma cell line PLC/PRF/5, it is difficult to obtain the large amounts of viral antigen required for diagnosis and vaccine development. In this study, we expressed N-terminal 13 and 111 aa-truncated rabbit HEV ORF2 proteins using recombinant baculoviruses and obtained two types of virus-like particles (VLPs), RnVLPs and RsVLPs with ~35 and 24 nm diameter, respectively. Anti-rabbit HEV IgG antibodies were induced in high titer by immunizing rabbits with RnVLPs or RsVLPs. The antibody secretion in the serum persisted more than three years. RsVLPs showed stronger antigenic cross-reactivity against HEV-1, HEV-3 and HEV-4 than rat HEV. Moreover, anti-RsVLPs antibodies neutralized not only the cognate virus but also HEV-1, HEV-3 and HEV-4 ex vivo, indicating that rabbit HEV had the same serotype as human HEVs. In contrast, the antibody did not block rat HEV infection, demonstrating that rat HEV belonged to a different serotype. Animal experiments indicated that immunization with either RnVLPs or RsVLPs completely protected the rabbits from challenge by rabbit HEV, suggesting that the VLPs are candidates for rabbit HEV vaccine development.

scholarly journals Classification, structure and molecular diagnostics of avian hepatitis E virus

2019 ◽  
Vol 75 (02) ◽  
pp. 6228-2019
Author(s):  
JOANNA NERC ◽  
PIOTR SZELESZCZUK
Keyword(s):  
Hepatitis E Virus ◽  
Rna Virus ◽  
Genetic Material ◽  
Hepatitis E ◽  
Open Reading Frames ◽  
Aetiological Factor ◽  
Base Pairs ◽  
Avian Hepatitis E Virus ◽  
And Function ◽  
Overlapping Open Reading Frames

Pathological syndromes caused by avian hepatitis E virus have been described as big liver and spleen disease; necrotic haemorrhagic hepatitis-splenomegaly syndrome; necrotic, haemorrhagic, hepatomegalic hepatitis; or hepatitis-liver haemorrhage syndrome. The aetiological factor of this syndrome belongs to the Hepeviridae family. Avian hepatitis E virus is a single-strand RNA virus whose genome consists of approx. 7,200 base pairs and contains a short non-coding 5’ terminus (27-35 nucleotides) followed by three partially overlapping open reading frames: ORF1, ORF3 and ORF2. Since the avian strains of hepatitis viruses do not replicate in cell cultures, molecular biology techniques are used in the diagnosis of infections. This article discusses in detail the structure and function of each ORF of avian hepatitis E virus, as well as methods for the identification of the genetic material of this pathogen.

scholarly journals Genotype-Specific Evolution of Hepatitis E Virus

2017 ◽  
Vol 91 (9) ◽  
Author(s):  
Adam B. Brayne ◽  
Bethany L. Dearlove ◽  
James S. Lester ◽  
Sergei L. Kosakovsky Pond ◽  
Simon D. W. Frost
Keyword(s):  
Positive Selection ◽  
Hepatitis E Virus ◽  
Hepatitis E ◽  
Open Reading Frames ◽  
Genotype 1 ◽  
Natural Case ◽  
Evolutionary Changes ◽  
Single Host ◽  
Multiple Species ◽  
Reading Frames

ABSTRACT Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis globally. HEV comprises four genotypes with different geographic distributions and host ranges. We utilize this natural case-control study for investigating the evolution of zoonotic viruses compared to single-host viruses, using 244 near-full-length HEV genomes. Genome-wide estimates of the ratio of nonsynonymous to synonymous evolutionary changes (dN/dS ratio) located a region of overlapping reading frames, which is subject to positive selection in genotypes 3 and 4. The open reading frames (ORFs) involved have functions related to host-pathogen interaction, so genotype-specific evolution of these regions may reflect their fitness. Bayesian inference of evolutionary rates shows that genotypes 3 and 4 have significantly higher rates than genotype 1 across all ORFs. Reconstruction of the phylogenies of zoonotic genotypes demonstrates significant intermingling of isolates between hosts. We speculate that the genotype-specific differences may result from cyclical adaptation to different hosts in genotypes 3 and 4. IMPORTANCE Hepatitis E virus (HEV) is increasingly recognized as a pathogen that affects both the developing and the developed world. While most often clinically mild, HEV can be severe or fatal in certain demographics, such as expectant mothers. Like many other viral pathogens, HEV has been classified into several distinct genotypes. We show that most of the HEV genome is evolutionarily constrained. One locus of positive selection is unusual in that it encodes two distinct protein products. We are the first to detect positive selection in this overlap region. Genotype 1, which infects humans only, appears to be evolving differently from genotypes 3 and 4, which infect multiple species, possibly because genotypes 3 and 4 are unable to achieve the same fitness due to repeated host jumps.

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

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhaobin Zhou ◽  
Yinqian Xie ◽  
Chunyan Wu ◽  
Yuchen Nan
Keyword(s):  
Hepatitis E Virus ◽  
Hepatitis E ◽  
Open Reading Frames ◽  
Viral Capsid ◽  
Reading Frame ◽  
Host Tropism ◽  
Orf2 Protein ◽  
Acute Hepatitis E ◽  
Open Reading Frame 2 ◽  
Reading Frames

Hepatitis E virus (HEV) is a zoonotic pathogen causing hepatitis in both human and animal hosts, which is responsible for acute hepatitis E outbreaks worldwide. The 7.2 kb genome of the HEV encodes three well-defined open reading frames (ORFs), where the ORF2 translation product acts as the major virion component to form the viral capsid. In recent years, besides forming the capsid, more functions have been revealed for the HEV-ORF2 protein, and it appears that HEV-ORF2 plays multiple functions in both viral replication and pathogenesis. In this review, we systematically summarize the recent research advances regarding the function of the HEV-ORF2 protein such as application in the development of a vaccine, regulation of the innate immune response and cellular signaling, involvement in host tropism and participation in HEV pathogenesis as a novel secretory factor. Progress in understanding more of the function of HEV-ORF2 protein beyond the capsid protein would contribute to improved control and treatment of HEV infection.

scholarly journals Characterization of a Novel Rat Hepatitis E Virus Isolated from an Asian Musk Shrew (Suncus murinus)

Viruses ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 715
Author(s):  
Huimin Bai ◽  
Wei Li ◽  
Dawei Guan ◽  
Juan Su ◽  
Changwen Ke ◽  
...  
Keyword(s):  
Hepatitis E Virus ◽  
Hepatitis E ◽  
Open Reading Frames ◽  
Entire Genome ◽  
Musk Shrew ◽  
Recovered Virus ◽  
Reading Frames ◽  
New Reservoir

The Asian musk shrew (shrew) is a new reservoir of a rat hepatitis E virus (HEV) that has been classified into genotype HEV-C1 in the species Orthohepevirus C. However, there is no information regarding classification of the new rat HEV based on the entire genome sequences, and it remains unclear whether rat HEV transmits from shrews to humans. We herein inoculated nude rats (Long-Evans rnu/rnu) with a serum sample from a shrew trapped in China, which was positive for rat HEV RNA, to isolate and characterize the rat HEV distributed in shrews. A rat HEV strain, S1129, was recovered from feces of the infected nude rat, indicating that rat HEV was capable of replicating in rats. S1129 adapted and grew well in PLC/PRF/5 cells, and the recovered virus (S1129c1) infected Wistar rats. The entire genomes of S1129 and S1129c1 contain four open reading frames and share 78.3–81.8% of the nucleotide sequence identities with known rat HEV isolates, demonstrating that rat HEVs are genetically diverse. We proposed that genotype HEV-C1 be further classified into subtypes HEV-C1a to HEV-C1d and that the S1129 strain circulating in the shrew belonged to the new subtype HEV-C1d. Further studies should focus on whether the S1129 strain infects humans.

scholarly journals A Bicistronic Subgenomic mRNA Encodes both the ORF2 and ORF3 Proteins of Hepatitis E Virus

2006 ◽  
Vol 80 (12) ◽  
pp. 5919-5926 ◽  
Author(s):  
Judith Graff ◽  
Udana Torian ◽  
Hanh Nguyen ◽  
Suzanne U. Emerson
Keyword(s):  
Resistance Gene ◽  
Cell Lines ◽  
Northern Blot ◽  
Hepatitis E Virus ◽  
Hepatitis E ◽  
Open Reading Frames ◽  
Subgenomic Rna ◽  
Neomycin Resistance Gene ◽  
Neomycin Resistance ◽  
Reading Frames

ABSTRACT Hepatitis E virus replicons containing the neomycin resistance gene expressed from open reading frames (ORFs) 2 and 3 were transfected into Huh-7 cells, and stable cell lines containing functional replicons were selected by constant exposure to G418 sulfate. Northern blot analyses detected full-length replicon RNA and a single subgenomic RNA. This subgenomic RNA, which was capped, initiated at nucleotide 5122 downstream of the first two methionine codons in ORF3 and was bicistronic; two closely spaced methionine codons in different reading frames were used for the initiation of ORF3 and ORF2 translation.

scholarly journals Efficient Production of Chimeric Hepatitis B Virus-Like Particles Bearing an Epitope of Hepatitis E Virus Capsid by Transient Expression in Nicotiana benthamiana

Life ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 64
Author(s):  
Gergana Zahmanova ◽  
Milena Mazalovska ◽  
Katerina Takova ◽  
Valentina Toneva ◽  
Ivan Minkov ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Nicotiana Benthamiana ◽  
Hepatitis E Virus ◽  
Chimeric Protein ◽  
Hepatitis E ◽  
Core Antigen ◽  
Efficient Production ◽  
Virus Like Particles ◽  
B Virus

The core antigen of hepatitis B virus (HBcAg) is capable of self-assembly into virus-like particles (VLPs) when expressed in a number of heterologous systems. Such VLPs are potential carriers of foreign antigenic sequences for vaccine design. In this study, we evaluated the production of chimeric HBcAg VLPs presenting a foreign epitope on their surface, the 551–607 amino acids (aa) immunological epitope of the ORF2 capsid protein of hepatitis E virus. A chimeric construct was made by the insertion of 56 aa into the immunodominant loop of the HBcAg. The sequences encoding the chimera were inserted into the pEAQ-HT vector and infiltrated into Nicotiana benthamiana leaves. The plant-expressed chimeric HBcHEV ORF2 551–607 protein was recognized by an anti-HBcAg mAb and anti-HEV IgG positive swine serum. Electron microscopy showed that plant-produced chimeric protein spontaneously assembled into “knobbly” ~34 nm diameter VLPs. This study shows that HBcAg is a promising carrier platform for the neutralizing epitopes of hepatitis E virus (HEV) and the chimeric HBcAg/HEV VLPs could be a candidate for a bivalent vaccine.

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