Julia Melchert , Helena Radbruch , Leif G. Hanitsch , Sally A. Baylis , Jörn Beheim-Schwarzbach , Tobias Bleicker , Jörg Hofmann , Terry C. Jones , Christian Drosten , Victor M. Corman
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However, HTS is challenged by factors including low viral load, sample degradation, high host background, and high viral diversity.</p></div><div><h3>Study design</h3><p>We apply complete genome sequencing strategies for HEV, including a targeted enrichment approach. These approaches were used to investigate sequence diversity in HEV RNA-positive animal and human samples and intra-host diversity in a chronically infected patient.</p></div><div><h3>Results</h3><p>Here, we describe the identification of potential novel subtypes in a blood donation (genotype 3) and in an ancient livestock sample (genotype 7). In a chronically infected patient, we successfully investigated intra-host virus diversity, including the presence of ribavirin resistance mutations. Furthermore, we found convincing evidence for HEV compartmentalization, including the central nervous system, in this patient.</p></div><div><h3>Conclusions</h3><p>Targeted enrichment of viral sequences enables the generation of complete genome sequences from a variety of difficult sample materials. Moreover, it enables the generation of greater sequence coverage allowing more advanced analyses. This is key for a better understanding of virus diversity. Investigation of existing ribavirin resistance, in the context of minorities or compartmentalization, may be critical in treatment strategies of HEV patients.</p></div>","PeriodicalId":15517,"journal":{"name":"Journal of Clinical Virology","volume":null,"pages":null},"PeriodicalIF":4.0000,"publicationDate":"2023-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Whole genome sequencing reveals insights into hepatitis E virus genome diversity, and virus compartmentalization in chronic hepatitis E\",\"authors\":\"Julia Melchert , Helena Radbruch , Leif G. Hanitsch , Sally A. Baylis , Jörn Beheim-Schwarzbach , Tobias Bleicker , Jörg Hofmann , Terry C. Jones , Christian Drosten , Victor M. 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Whole genome sequencing reveals insights into hepatitis E virus genome diversity, and virus compartmentalization in chronic hepatitis E
Background
Hepatitis E virus (HEV) is a leading cause of acute hepatitis and can cause chronic infections in immunocompromised patients. Although HEV infections can be treated with ribavirin, antiviral efficacy is hampered by resistance mutations, normally detected by virus sequencing.
Objectives
High-throughput sequencing (HTS) allows for cost-effective complete viral genome sequencing. This enables the discovery and delineation of new subtypes, and revised the recognition of quasispecies and putative resistance mutations. However, HTS is challenged by factors including low viral load, sample degradation, high host background, and high viral diversity.
Study design
We apply complete genome sequencing strategies for HEV, including a targeted enrichment approach. These approaches were used to investigate sequence diversity in HEV RNA-positive animal and human samples and intra-host diversity in a chronically infected patient.
Results
Here, we describe the identification of potential novel subtypes in a blood donation (genotype 3) and in an ancient livestock sample (genotype 7). In a chronically infected patient, we successfully investigated intra-host virus diversity, including the presence of ribavirin resistance mutations. Furthermore, we found convincing evidence for HEV compartmentalization, including the central nervous system, in this patient.
Conclusions
Targeted enrichment of viral sequences enables the generation of complete genome sequences from a variety of difficult sample materials. Moreover, it enables the generation of greater sequence coverage allowing more advanced analyses. This is key for a better understanding of virus diversity. Investigation of existing ribavirin resistance, in the context of minorities or compartmentalization, may be critical in treatment strategies of HEV patients.
期刊介绍:
The Journal of Clinical Virology, an esteemed international publication, serves as the official journal for both the Pan American Society for Clinical Virology and The European Society for Clinical Virology. Dedicated to advancing the understanding of human virology in clinical settings, the Journal of Clinical Virology focuses on disseminating research papers and reviews pertaining to the clinical aspects of virology. Its scope encompasses articles discussing diagnostic methodologies and virus-induced clinical conditions, with an emphasis on practicality and relevance to clinical practice.
The journal publishes on topics that include:
• new diagnostic technologies
• nucleic acid amplification and serologic testing
• targeted and metagenomic next-generation sequencing
• emerging pandemic viral threats
• respiratory viruses
• transplant viruses
• chronic viral infections
• cancer-associated viruses
• gastrointestinal viruses
• central nervous system viruses
• one health (excludes animal health)