AI Article Synopsis
- Hepatitis B virus (HBV) infects about 296 million people and has a compact genome with overlapping protein-coding regions, making it subject to various evolutionary pressures.
- This study uses a specialized HBV cell culture system and deep mutational scanning to investigate the specific sequence requirements of the HBV genome, particularly concerning the polymerase.
- Findings reveal a ribosome scanning model for translating the polymerase, mapping its fitness at a single-nucleotide level, and show how stalled ribosomes help ensure efficient packaging and transcription of the HBV RNA.
Article Abstract
Hepatitis B virus (HBV) is a small double-stranded DNA virus that chronically infects 296 million people. Over half of its compact genome encodes proteins in two overlapping reading frames, and during evolution, multiple selective pressures can act on shared nucleotides. This study combines an RNA-based HBV cell culture system with deep mutational scanning (DMS) to uncouple cis- and trans-acting sequence requirements in the HBV genome. The results support a leaky ribosome scanning model for polymerase translation, provide a fitness map of the HBV polymerase at single-nucleotide resolution, and identify conserved prolines adjacent to the HBV polymerase termination codon that stall ribosomes. Further experiments indicated that stalled ribosomes tether the nascent polymerase to its template RNA, ensuring cis-preferential RNA packaging and reverse transcription of the HBV genome.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11127778 | PMC |
| http://dx.doi.org/10.1016/j.cell.2024.04.008 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!