Recent Advances in Hepatitis E Virus
Recent Advances in Hepatitis E Virus
Hepatitis E virus (HEV), the causative agent of hepatitis E, belongs to the family Hepeviridae. At least four major genotypes of HEV have been recognized: genotypes 1 and 2 are restricted to humans and associated with epidemics in developing countries, whereas genotypes 3 and 4 are zoonotic and infect humans and several other animals in both developing and industrialized countries. Besides humans, strains of HEV have been genetically identified from swine, chickens, sika deer, mongeese, and rabbits. The genome of HEV consists of three open reading frames (ORFs): ORF1 codes for nonstructural proteins, ORF2 codes for capsid protein, and ORF3 codes for a small multifunctional protein. The ORF2 and ORF3 proteins are translated from a single bicistronic mRNA and overlap each other but neither overlaps ORF1. The recent determination of the 3D crystal structure of the HEV capsid protein should facilitate the development of vaccines and antivirals. The identification and characterization of animal strains of HEV from pigs and chickens and the demonstrated ability of cross-species infection by swine HEV raise public health concerns for zoonosis. Accumulating evidence indicated that hepatitis E is a zoonotic disease and pigs and more likely other animal species are reservoirs for HEV. This article provides an overview of the recent advances in hepatitis E and its causative agent, including nomenclature and genomic organization, gene expression and functions, 3D structure of the virions, changing perspectives on higher mortality during pregnancy and chronic hepatitis E, animal reservoirs, zoonotic risk, food safety, and novel animal models.
Hepatitis E is an important public health disease in many developing countries of Asia and Africa. Sporadic cases of hepatitis E have also been reported in many industrialized countries. A unique feature of hepatitis E is the relatively high mortality rate reported during pregnancy. The causative agent, hepatitis E virus (HEV), is a small nonenveloped RNA virus that is transmitted primarily via the faecal–oral route. In the past decade or so, progress has been made in understanding the epidemiology, natural history, animal reservoirs, pathogenesis, structure, and molecular biology of HEV. The recent discovery of animal strains of HEV from pigs, chickens, rabbits, deer, and mongeese, and the existence of other animal species seropositive for HEV antibodies has broadened the host range and diversity of HEV. Hepatitis E is now a recognized zoonotic disease, and pigs and more likely other animal species are reservoirs for HEV. The successful construction of HEV infectious clones and the identification of cell lines supporting a limited level of HEV replication provided useful tools to dissect the structural and functional relationship of HEV genes. The development of small animal models for HEV, pigs and chickens, affords the opportunity to define the molecular basis of HEV replication and pathogenesis. The determination of the 3D crystal structure of HEV capsid protein will help rationally design effective vaccines and antivirals against HEV in the future.
This article provides an overview of the recent advances in hepatitis E and its causative agent, including new nomenclature and genomic organization, gene expression and functions, 3D structure of the virions, changing perspectives on higher mortality during pregnancy and chronic hepatitis E, animal reservoirs, cross-species infection and zoonotic risk, food safety, and novel animal models. Despite recent advances, HEV remains an extremely understudied, but important, human pathogen.
Abstract and Introduction
Abstract
Hepatitis E virus (HEV), the causative agent of hepatitis E, belongs to the family Hepeviridae. At least four major genotypes of HEV have been recognized: genotypes 1 and 2 are restricted to humans and associated with epidemics in developing countries, whereas genotypes 3 and 4 are zoonotic and infect humans and several other animals in both developing and industrialized countries. Besides humans, strains of HEV have been genetically identified from swine, chickens, sika deer, mongeese, and rabbits. The genome of HEV consists of three open reading frames (ORFs): ORF1 codes for nonstructural proteins, ORF2 codes for capsid protein, and ORF3 codes for a small multifunctional protein. The ORF2 and ORF3 proteins are translated from a single bicistronic mRNA and overlap each other but neither overlaps ORF1. The recent determination of the 3D crystal structure of the HEV capsid protein should facilitate the development of vaccines and antivirals. The identification and characterization of animal strains of HEV from pigs and chickens and the demonstrated ability of cross-species infection by swine HEV raise public health concerns for zoonosis. Accumulating evidence indicated that hepatitis E is a zoonotic disease and pigs and more likely other animal species are reservoirs for HEV. This article provides an overview of the recent advances in hepatitis E and its causative agent, including nomenclature and genomic organization, gene expression and functions, 3D structure of the virions, changing perspectives on higher mortality during pregnancy and chronic hepatitis E, animal reservoirs, zoonotic risk, food safety, and novel animal models.
Introduction
Hepatitis E is an important public health disease in many developing countries of Asia and Africa. Sporadic cases of hepatitis E have also been reported in many industrialized countries. A unique feature of hepatitis E is the relatively high mortality rate reported during pregnancy. The causative agent, hepatitis E virus (HEV), is a small nonenveloped RNA virus that is transmitted primarily via the faecal–oral route. In the past decade or so, progress has been made in understanding the epidemiology, natural history, animal reservoirs, pathogenesis, structure, and molecular biology of HEV. The recent discovery of animal strains of HEV from pigs, chickens, rabbits, deer, and mongeese, and the existence of other animal species seropositive for HEV antibodies has broadened the host range and diversity of HEV. Hepatitis E is now a recognized zoonotic disease, and pigs and more likely other animal species are reservoirs for HEV. The successful construction of HEV infectious clones and the identification of cell lines supporting a limited level of HEV replication provided useful tools to dissect the structural and functional relationship of HEV genes. The development of small animal models for HEV, pigs and chickens, affords the opportunity to define the molecular basis of HEV replication and pathogenesis. The determination of the 3D crystal structure of HEV capsid protein will help rationally design effective vaccines and antivirals against HEV in the future.
This article provides an overview of the recent advances in hepatitis E and its causative agent, including new nomenclature and genomic organization, gene expression and functions, 3D structure of the virions, changing perspectives on higher mortality during pregnancy and chronic hepatitis E, animal reservoirs, cross-species infection and zoonotic risk, food safety, and novel animal models. Despite recent advances, HEV remains an extremely understudied, but important, human pathogen.
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