Analysis of codon usage patterns in open reading frame 4 of hepatitis E viruses

Area of Science:

• Virology
• Bioinformatics
• Molecular Biology

Background:

• Hepatitis E virus (HEV) causes significant global mortality, particularly in pregnant women.
• A recently discovered ORF4 protein in HEV genotype 1 is implicated in pregnancy-associated pathology and replication.
• Understanding the genetic features, specifically codon usage patterns, of HEV ORF4 is crucial for elucidating host-pathogen interactions.

Purpose of the Study:

• To perform a comprehensive codon usage analysis of HEV ORF4 protein genes.
• To investigate the factors influencing codon usage patterns in HEV ORF4 across different hosts (human, rat, ferret).
• To provide insights into the evolutionary dynamics of HEV ORF4.

Main Methods:

• Analysis of nucleotide sequences of HEV ORF4 obtained from public databases.
• Assessment of nucleotide composition, including the representation of C, A, G, and T(U) nucleotides.
• Relative Synonymous Codon Usage (RSCU) analysis to identify codon bias.
• Evaluation of the influence of mutational and selection forces on codon usage patterns.

Main Results:

• HEV ORF4 protein genes exhibit overrepresentation of the nucleotide C and underrepresentation of A.
• A significant bias towards C/G-ended codons (over U/A) was observed in all studied hosts.
• The GC content was found to be high in all ORF4 genes.
• Both coincidental and antagonistic codon usage patterns were identified among different HEV hosts, indicating complex evolutionary pressures.

Conclusions:

• This is the first bioinformatics study to examine codon usage patterns in HEV ORF4 protein genes.
• The findings highlight the significant roles of both mutational and selection forces in shaping HEV ORF4 codon usage.
• The study enhances understanding of the evolutionary factors driving changes in HEV ORF4.