Phylogeographic and Host Interface Analyses Reveal the Evolutionary Dynamics of SAT3 Foot-And-Mouth Disease Virus

Foot-and-mouth disease virus (FMDV) serotype SAT3 is a rarely studied serotype primarily circulating in southern Africa, with African buffalo (<i>Syncerus caffer</i>) serving as its key reservoir. In this study, we performed a comprehensive phylogenetic and phylodynamic analysis of SAT3 based on 81 full-length VP1 gene sequences collected between 1934 and 2018. Maximum likelihood and Bayesian analyses revealed five distinct topotypes, each with clear geographic and host associations. Notably, topotypes I, II and III were observed in both African buffalo and cattle (<i>Bos taurus</i>), while topotype IV appeared restricted to African buffalo. Likelihood mapping indicated moderate to strong phylogenetic signal, and the mean substitution rate was estimated at 3.709 × 10^-3 substitutions/site/year under a relaxed molecular clock. The time to the most recent common ancestor (TMRCA) was traced back to 1875. Discrete phylogeographic reconstruction identified Zimbabwe as a major center, with multiple supported cross-border transmission routes. Host transition analysis further confirmed strong directional flow from buffalo to cattle (BF = 1631.09, pp = 1.0), highlighting the wildlife-livestock interface as a key driver of SAT3 persistence. Together, these results underscore the evolutionary complexity of SAT3 and the importance of integrating molecular epidemiology, spatial modeling, and host ecology to inform FMD control strategies in endemic regions.