Suboptimal dengue genome leverages non-canonical translation mechanisms

Dengue is a notable example of vector-borne RNA virus responsible for severe hemorrhagic fever. Its compact genome necessitates reliance on the host's translational machinery for replication. This study investigates the plausible adaptive strategies employed by dengue serotypes for effective translation within the human host. By analyzing viral reads from the RNA-seq dataset derived from the hospital-admitted patients, we explored the impact of dinucleotide diversity on codon optimization, and compatibility of serotypes with the host. Our findings reveal only moderate congruency of serotypes with the host and identified genomic composition common to several RNA viruses. Notably, unique coverage patterns were observed within the genome of DENV-2 serotypes. Using ribosome profileing (Ribo-seq) data, we extended our analysis to assess the translatability of potential internal open reading frames (iORFs) identified in the RNA-seq dataset. Nine common iORFs were identified across both the datasets, underscoring potential non-canonical translational mechanisms that might enhance DENV genome optimization.