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 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 Comprehensive analysis of genetic and evolutionary features of the hepatitis E virus

BMC Genomics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Sarra Baha ◽  
Nouredine Behloul ◽  
Zhenzhen Liu ◽  
Wenjuan Wei ◽  
Ruihua Shi ◽  
...  
Keyword(s):  
Natural Selection ◽  
Codon Usage ◽  
Hepatitis E Virus ◽  
Hepatitis E ◽  
Open Reading Frames ◽  
Health Concern ◽  
Global Public Health ◽  
Genotype 1 ◽  
Mutation Pressure ◽  
Evolutionary Features

Abstract Background The hepatitis E virus (HEV) is the causative pathogen of hepatitis E, a global public health concern. HEV comprises 8 genotypes with a wide host range and geographic distribution. This study aims to determine the genetic factors influencing the molecular adaptive changes of HEV open reading frames (ORFs) and estimate the HEV origin and evolutionary history. Results Sequences of HEV strains isolated between 1982 and 2017 were retrieved and multiple analyses were performed to determine overall codon usage patterns, effects of natural selection and/or mutation pressure and host influence on the evolution of HEV ORFs. Besides, Bayesian Coalescent Markov Chain Monte Carlo (MCMC) Analysis was performed to estimate the spatial-temporal evolution of HEV. The results indicated an A/C nucleotide bias and ORF-dependent codon usage bias affected mainly by natural selection. The adaptation of HEV ORFs to their hosts was also ORF-dependent, with ORF1 and ORF2 sharing an almost similar adaptation profile to the different hosts. The discriminant analysis based on the adaptation index suggested that ORF1 and ORF3 could play a pivotal role in viral host tropism. Conclusion In this study, we estimate that the common ancestor of the modern HEV strains emerged ~ 6000 years ago, in the period following the domestication of pigs. Then, natural selection played the major role in the evolution of the codon usage of HEV ORFs. The significant adaptation of ORF1 of genotype 1 to humans, makes ORF1 an evolutionary indicator of HEV host speciation, and could explain the epidemic character of genotype 1 strains in humans.

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 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 Complete Genome Sequence of a Hepatitis E Virus Genotype 1e Strain from an Outbreak in Nigeria, 2017

2019 ◽  
Vol 8 (1) ◽  
Author(s):  
Olusola Anuoluwapo Akanbi ◽  
Dominik Harms ◽  
Bo Wang ◽  
Oluyinka Oladele Opaleye ◽  
Olufisayo Adesina ◽  
...  
Keyword(s):  
Genome Sequence ◽  
Complete Genome Sequence ◽  
Complete Genome ◽  
Hepatitis E Virus ◽  
Hepatitis E ◽  
Sub Saharan Africa ◽  
Genotype 1 ◽  
Virus Genotype ◽  
Sub Saharan

Hepatitis E virus genotype 1 (HEV-1) is associated with large epidemics. Notably, HEV subtype 1e (HEV-1e) has caused HEV outbreaks in sub-Saharan Africa.

scholarly journals Advances in Hepatitis E Virus Biology and Pathogenesis

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 267
Author(s):  
Shaoli Lin ◽  
Yan-Jin Zhang
Keyword(s):  
Pregnant Women ◽  
Hepatitis E Virus ◽  
Case Fatality ◽  
Hepatitis E ◽  
Host Cells ◽  
High Rate ◽  
Rapid Progression ◽  
Genotype 1 ◽  
Genotype 3 ◽  
Zoonotic Infections

Hepatitis E virus (HEV) is one of the causative agents for liver inflammation across the world. HEV is a positive-sense single-stranded RNA virus. Human HEV strains mainly belong to four major genotypes in the genus Orthohepevirus A, family Hepeviridae. Among the four genotypes, genotype 1 and 2 are obligate human pathogens, and genotype 3 and 4 cause zoonotic infections. HEV infection with genotype 1 and 2 mainly presents as acute and self-limiting hepatitis in young adults. However, HEV infection of pregnant women with genotype 1 strains can be exacerbated to fulminant hepatitis, resulting in a high rate of case fatality. As pregnant women maintain the balance of maternal-fetal tolerance and effective immunity against invading pathogens, HEV infection with genotype 1 might dysregulate the balance and cause the adverse outcome. Furthermore, HEV infection with genotype 3 can be chronic in immunocompromised patients, with rapid progression, which has been a challenge since it was reported years ago. The virus has a complex interaction with the host cells in downregulating antiviral factors and recruiting elements to generate a conducive environment of replication. The virus-cell interactions at an early stage might determine the consequence of the infection. In this review, advances in HEV virology, viral life cycle, viral interference with the immune response, and the pathogenesis in pregnant women are discussed, and perspectives on these aspects are presented.

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