Investigation of Codon Usage Signatures in Human Pathogenic Astrovirus Reveals Host Adaptation Dynamics

Abstract

Human astrovirus (HAstV) is a significant cause of viral gastroenteritis worldwide, especially affecting vulnerable populations such as children, the elderly, and individuals with weakened immune systems. Despite its global prevalence, the molecular strategies enabling HAstV to persist and thrive in human hosts remain poorly understood. This study takes a closer look at the codon usage patterns of HAstV to unravel its mechanisms of host adaptation and immune evasion.The analysis shows that HAstV exhibits a notable bias toward adenine (A) and uracil (U) nucleotides, with reduced usage of guanine (G) and cytosine (C), a pattern typical of many RNA viruses. Importantly, the HAstV's preferred codons closely align with the most abundant human transfer RNAs (tRNAs), indicating that translational selection strongly influences its codon choices. Supporting this, HAstV showed higher Codon Adaptation Index (CAI) and tRNA Adaptation Index (TAI) values, along with lower Relative Codon Deoptimization Index (RCDI), when compared to rotaviruses (used here as a control group). These indices collectively suggest that HAstV is more finely tuned for efficient translation within the human host than rotaviruses. Moreover, a consistent underrepresentation of CpG dinucleotides in HAstV genomes, a likely strategy to evade host immune detection mechanisms such as the ZAP protein or Toll-like receptors. These findings offer valuable insight into how HAstV balances replication efficiency with immune invisibility. Taken together, this research not only deepens our understanding of the evolutionary forces shaping astrovirus genomes but also highlights codon usage analysis as a promising avenue for rational vaccine design. Codon deoptimization—intentionally using rare or less efficient codons—could serve as a strategy to attenuate the virus while maintaining immunogenicity, paving the way for safe and effective vaccine development. By decoding how HAstV adapts to its host, we move closer to targeted antiviral solutions that could prevent future outbreaks and protect at-risk populations.