Phylodynamic and transmission pattern of rabies virus in China and its neighboring countries.

Rabies is a fatal disease caused by infection with rabies virus (RABV), and human rabies is still a critical public-health concern in China. Although there have been some phylogenetic studies about RABV transmission patterns, with the accumulation of more rabies sequences in recent years, there is an urgent need to update and clarify the spatial and temporal patterns of RABV circulating in China on a national scale. In this study, we collected all available RABV nucleoprotein gene sequences from China and its neighboring countries and performed comparative analysis. We identified six significant subclades of RABV circulating in China and found that each of them has a specific geographical distribution, reflecting possible physical barriers to gene flow. The phylogeographic analysis revealed minimal viral movement among different geographical locations. An analysis using Bayesian coalescent methods indicated that the current RABV strains in China may come from a common ancestor about 400 years ago, and currently, China is amid the second event of increasing RABV population since the 1950s, but the population has decreased gradually. We did not detect any evidence of recombination in the sequence dataset, nor did we find any evidence for positive selection during the expansion of RABV. Overall, geographic location and neutral genetic drift may be the main factors in shaping the phylogeography of RABV transmission in China.