Dengue virus preferentially uses human and mosquito non-optimal codons

Area of Science:

• Virology
• Genomics
• Molecular Biology

Background:

• Codon optimality influences messenger RNA (mRNA) stability and translation efficiency.
• Synonymous codons are not functionally equivalent and play regulatory roles.
• Dengue virus (DENV) is a mosquito-borne flavivirus with significant public health impact.

Purpose of the Study:

• Investigate the adaptation of virus genomes to host codon optimality.
• Utilize mosquito-borne dengue virus (DENV) as a model system.
• Determine if viruses preferentially use non-optimal codons and how this affects fitness.

Main Methods:

• Analysis of DENV genome codon usage in relation to human and mosquito codon optimality.
• Examination of host gene and tRNA expression during DENV infection.
• Assessment of synonymous mutation selection during virus passaging in cell culture.

Main Results:

• Codon optimality exists in mosquito cells.
• DENV preferentially uses non-optimal codons and avoids optimal codons of both hosts.
• Host genes and tRNAs associated with DENV's preferred codons are upregulated during infection.
• Virus adaptation involves selection of synonymous mutations towards non-optimal codons, increasing fitness.
• Hundreds of viruses, particularly single-host viruses, show a bias towards non-optimal codon usage.

Conclusions:

• Host-pathogen interactions shape virus synonymous codon choice.
• DENV's non-optimal codon usage is an adaptive strategy that enhances virus fitness.
• The findings suggest a broader evolutionary principle for virus adaptation across different hosts.