Abstract
Rabies virus (RABV) is a highly pathogenic virus that causes a fatal disease in humans and other mammals, but the mechanism of its evolution, spread, and spillover remains unknown. In this study, we analyzed the codon usage pattern of 2,018 RABV full-length genome sequences from 79 countries collected between 1931 and 2021 to provide an insight into its molecular evolution and unravel its unknown host-adapted pattern. We found that RABV exhibited a weak codon usage bias, with a preference for the codons ending in A (28.10 ± 0.01) or U (26.43 ± 0.02). Moreover, natural selection plays a major role in shaping the codon usage bias of the RABV. Notably, nearly half of the 18 codons in the virus were best matched to the hosts' most abundant isoacceptor tRNAs, which might account for the wide range of RABV hosts. Furthermore, significant differences were observed in the codon usage patterns of RABV for different host species, suggesting that codon usage bias may be influenced by host-specific factors. In conclusion, our study reveals codon usage patterns of RABV that may help in the development of control strategies and effective vaccines and therapies against this deadly virus.