A small stretch of poor codon usage at the beginning of dengue virus open reading frame may act as a translational checkpoint

Objective: Rare codons were previously shown to be enriched at the beginning of the dengue virus (DENV) open reading frame. However, the role of rare codons in regulating translation efficiency and replication of DENV remains unclear. The present study aims to clarify the significance of rare codon usage at the beginning of DENV transcripts using the codon adaptation index (CAI). Methodology: CAIs of the whole starting regions of DENV transcripts as well as 18-codon sliding windows of the regions were analyzed. Results: One of the intriguing findings is that those rare codons do not typically result in uniformly low CAI in the starting region with rare codons. However, it shows a notable local drop in CAI around the 50th codon in all dengue serotypes. This suggests that there may be a translational checkpoint at this site and that the rare codon usage upstream to this checkpoint may not be related to translational control.