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A Cell Culture Model for Producing High Titer Hepatitis E Virus Stocks
Published on: June 26, 2020
The hepatitis E virus polyproline region is involved in viral adaptation
Michael A Purdy1, James Lara, Yury E Khudyakov
1Centers for Disease Control and Prevention, National Center for HIV/Hepatitis/STD/TB Prevention, Division of Viral Hepatitis, Atlanta, Georgia, United States of America. mup3@cdc.gov
Plos One
|May 1, 2012
Summary
The polyproline region (PPR) in hepatitis E virus (HEV) shows high variability and is crucial for host adaptation. This intrinsically disordered region (IDR) may be a target for new antiviral drugs.
Area of Science:
- Virology
- Molecular Biology
- Evolutionary Biology
Background:
- Hepatitis E virus (HEV), rubivirus, and cutthroat virus (CTV) genomes share a unique polyproline region (PPR).
- The PPR in HEV genotypes 1, 3, and 4 is the sole region in ORF1 exhibiting positive selection and high homoplasy.
Purpose of the Study:
- To investigate the role of the polyproline region (PPR) in HEV adaptation and viral replication.
- To explore the structural and functional characteristics of the PPR as a potential antiviral target.
Main Methods:
- Comparative genomic analysis of HEV, rubivirus, and CTV.
- Analysis of positive selection, homoplasy density, and sequence divergence within the PPR.
- Secondary and tertiary structure prediction to identify the PPR as an intrinsically disordered region (IDR).
- Identification and structure-based analysis of putative linear binding motifs within the PPR.
Main Results:
- The PPR is a hypervariable and homoplastic region, with higher homoplastic density and divergence in HEV genotypes 3 and 4 compared to genotype 1.
- Phylogenetic analysis indicates convergent evolution within HEV lineages.
- The PPR is identified as an intrinsically disordered region (IDR) with a propensity for disorder-to-order transitions, suggesting involvement in protein-protein interactions.
- Seven putative linear binding motifs within the PPR suggest interaction with various cellular ligands and signaling pathways.
Conclusions:
- The PPR plays a significant role in HEV host-range adaptation.
- As an IDR, the PPR likely fine-tunes viral replication via protein-protein interactions.
- The PPR represents a promising target for the development of novel antiviral therapies against HEV.
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