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Kinetics of Lagging-strand DNA Synthesis In Vitro by the Bacteriophage T7 Replication Proteins
Published on: February 25, 2017
7.8K
CpG and UpA dinucleotides in both coding and non-coding regions of echovirus 7 inhibit replication initiation
Jelke Jan Fros1, Isabelle Dietrich1, Kinda Alshaikhahmed1
1Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
Elife
|September 30, 2017
Summary
Viruses suppress CpG and UpA dinucleotides to mimic host mRNA. Increasing these dinucleotides in viruses like echovirus 7 (E7) restricts replication via an unknown intrinsic host defense mechanism, independent of translation efficiency.
Area of Science:
- Virology
- Molecular Biology
- Immunology
Background:
- Vertebrate and plant viruses often suppress CpG and UpA dinucleotide frequencies.
- This suppression is thought to mimic host messenger RNA (mRNA) composition.
- Artificial increases in CpG/UpA dinucleotides can attenuate viruses through an unknown mechanism.
Purpose of the Study:
- To investigate the mechanism by which increased CpG/UpA dinucleotides restrict viral replication.
- To determine if this restriction is linked to translation efficiency or other cellular processes.
Main Methods:
- Utilized echovirus 7 (E7) mutants with increased CpG/UpA dinucleotides in various cell types.
- Analyzed viral replication, RNA sequences, mutational errors, cytoplasmic stress granule localization, and induction of antiviral states.
- Assessed replication efficiency of replicons with high CpG/UpA sequences in non-coding regions.
Main Results:
- Restriction of E7 replication with increased CpG/UpA occurred immediately post-entry, preventing replication complex formation.
- Viral RNA sequences showed no increased mutational errors, were not sequestered in stress granules, and did not induce an antiviral state.
- Replicons with high CpG/UpA in non-coding regions were also replication defective, indicating independence from translation efficiency.
Conclusions:
- Host cells possess intrinsic defense pathways that restrict viral replication based on CpG/UpA dinucleotide frequencies.
- This restriction mechanism is independent of codon usage and translation efficiency.
- The findings reveal a novel host-virus interaction impacting early viral replication stages.
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