| Summary: | 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.
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