Codon Usage Evolution in Viruses: Implications for Survival and Pathogenicity

Abstract

Codon usage serves as a fundamental viral signature, influencing survival, adaptation, and pathogenicity. Viruses exhibit distinct codon usage patterns shaped by genome composition, host interactions, and evolutionary pressures. The differences between DNA and RNA viruses in codon usage reflect their replication strategies, host preferences, and genome constraints. Viral adaptation to host codon usage, genome size, and lifestyle further shapes translational efficiency and immune evasion mechanisms. Host tRNA abundance plays a crucial role in viral translation rates, while codon deoptimization is a strategy used by viruses to evade immune detection. Additionally, codon bias is linked to viral virulence, replication rates, and pathogenicity. Building on these concepts, this review synthesizes current knowledge on the interplay between virus-host translational interactions, codon bias-driven viral evolution, and their implications for pathogenesis, immune evasion, and epidemiology, while also outlining their practical applications in vaccine development, antiviral strategies, and viral diagnostics. We discuss current challenges in codon usage studies, including context-dependent variations and limited experimental validation, and propose future research directions that integrate computational and experimental approaches to deepen our understanding of viral codon bias and its role in evolution, host adaptation, and disease control.

Keywords: Codon; Evolution; Vaccine; Viral codon usage; Zoonotic spillover.