RNA editing signatures and codon adaptation reveal potential translational compatibility between Hendra virus and its natural host Pteropus Alecto.

The Hendra virus (HeV), a very lethal zoonotic pathogen, demonstrates complex evolutionary dynamics with its natural reservoir, Pteropus alecto. This study meticulously compares codon usage bias (CUB), dinucleotide frequencies, RNA editing patterns, and the Relative Codon Deoptimization Index (RCDI) to elucidate virus–host co-adaptation. The average Effective Number of Codons (ENC) data showed very little bias in codon usage, which indicates potential translational compatibility. Even though HeV and P. alecto had different nucleotide compositions, both genomes showed the same CpG suppression and a preference for certain codons, including AGG. Amino acid profile showed that leucine was the most common amino acid, and tryptophan was the least common. The relative synonymous codon usage (RSCU) study indicated unique yet intersecting codon preferences in both the virus and the host. Evolutionary investigations employing ENC–GC3, parity rule 2, and neutrality plots indicated that natural selection mostly influences viral codon usage, while host codon bias is principally affected by mutational pressure. Analysis of RNA editing sites showed that C-to-T transitions were the most common, followed by A-to-G modifications. This shows how host-mediated editing mechanisms play a role in viral evolution. The RCDI analysis provided additional evidence for the moderate translational adaptation of HeV to P. alecto. Together, these results improve our knowledge of how viruses and hosts interact at the molecular level and give us possible targets for monitoring and intervention.