A specific base transition occurs on replicating hepatitis delta virus RNA.

Area of Science:

• Virology
• Molecular Biology
• Hepatitis Delta Virus Research

Background:

• Hepatitis delta virus (HDV) is a unique RNA virus that requires coinfection with hepatitis B virus for its replication.
• The delta antigen's open reading frame (ORF) contains a critical amber termination codon.

Purpose of the Study:

• To investigate mutations occurring during hepatitis delta virus genome replication.
• To determine the impact of these mutations on the delta antigen's protein structure.

Main Methods:

• Utilized an infectious clone of hepatitis delta virus with a known sequence.
• Initiated genome replication using the infectious clone.
• Analyzed viral genomes for specific mutations using multiple independent lines of evidence.
• Focused on mutations within the amber termination codon of the delta antigen ORF.

Main Results:

• Observed specific mutations in the amber termination codon (UAG to UGG) in up to 41% of replicated HDV genomes.
• This mutation extended the predicted delta antigen protein length from 195 to 214 amino acids.
• The observed mutation was exclusively detected in RNA molecules involved in RNA-directed RNA synthesis.

Conclusions:

• Genome replication of hepatitis delta virus can lead to specific alterations in the delta antigen's coding sequence.
• These alterations, particularly the readthrough of the amber termination codon, result in a longer delta antigen protein.
• The mutation is linked to the viral RNA replication process, suggesting a mechanism related to RNA-directed RNA synthesis.