Advanced sequencing approaches detected insertions of viral and human origin in the viral genome of chronic hepatitis E virus patients.
Sci Rep
; 12(1): 1720, 2022 02 02.
Article
in En
| MEDLINE
| ID: mdl-35110582
ABSTRACT
The awareness of hepatitis E virus (HEV) increased significantly in the last decade due to its unexpectedly high prevalence in high-income countries. There, infections with HEV-genotype 3 (HEV-3) are predominant which can progress to chronicity in immunocompromised individuals. Persistent infection and antiviral therapy can select HEV-3 variants; however, the spectrum and occurrence of HEV-3 variants is underreported. To gain in-depth insights into the viral population and to perform detailed characterization of viral genomes, we used a new approach combining long-range PCR with next-generation and third-generation sequencing which allowed near full-length sequencing of HEV-3 genomes. Furthermore, we developed a targeted ultra-deep sequencing approach to assess the dynamics of clinically relevant mutations in the RdRp-region and to detect insertions in the HVR-domain in the HEV genomes. Using this new approach, we not only identified several insertions of human (AHNAK, RPL18) and viral origin (RdRp-derived) in the HVR-region isolated from an exemplary sample but detected a variant containing two different insertions simultaneously (AHNAK- and RdRp-derived). This finding is the first HEV-variant recognized as such showing various insertions in the HVR-domain. Thus, this molecular approach will add incrementally to our current knowledge of the HEV-genome organization and pathogenesis in chronic hepatitis E.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
DNA, Viral
/
Mutagenesis, Insertional
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Hepatitis E virus
/
Hepatitis E
/
Genome, Viral
/
Sequence Analysis, DNA
/
Hepatitis, Chronic
Type of study:
Diagnostic_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
Sci Rep
Year:
2022
Document type:
Article
Affiliation country:
Germany