The classification, origin, and evolutionary dynamics of severe fever with thrombocytopenia syndrome virus circulating in East Asia

Abstract

The classification of severe fever with thrombocytopenia syndrome virus (SFTSV) lacked consistency due to limited virus sequences used across previous studies, and the origin and transmission dynamics of the SFTSV remains not fully understood. In this study, we analyzed the diversity and phylodynamics of SFTSV using the most comprehensive and largest dataset publicly available for a better understanding of SFTSV classification and transmission. A total of 1267 L segments, 1289 M segments, and 1438 S segments collected from China, South Korea, and Japan were included in this study. Maximum likelihood trees were reconstructed to classify the lineages. Discrete phylogeographic analysis was conducted to infer the phylodynamics of SFTSV. We found that the L, M, and S segments were highly conserved, with mean pairwise nucleotide distances of 2.80, 3.36, and 3.35% and could be separated into 16, 13, and 15 lineages, respectively. The evolutionary rate for L, M, and the S segment was 0.61 × 10^-4 (95% HPD: 0.48-0.73 × 10^-4), 1.31 × 10^-4 (95% HPD: 0.77-1.77 × 10^-4) and 1.27 × 10^-4 (95% HPD: 0.65-1.85 × 10^-4) subs/site/year. The SFTSV most likely originated from South Korea around the year of 1617.6 (95% HPD: 1513.1-1724.3), 1700.4 (95% HPD: 1493.7-1814.0), and 1790.1 (95% HPD: 1605.4-1887.2) for L, M, and S segments, respectively. Hubei Province in China played a critical role in the geographical expansion of the SFTSV. The effective population size of SFTSV peaked around 2010 to 2013. We also identified several codons under positive selection in the RdRp, Gn-Gc, and NS genes. By leveraging the largest dataset of SFTSV, our analysis could provide new insights into the evolution and dispersal of SFTSV, which may be beneficial for the control and prevention of severe fever with thrombocytopenia syndrome.

Keywords: diversity; origin; phylodynamics; selective pressure; severe fever with thrombocytopenia syndrome.

Figure 1.

The epidemiology of SFTSV sequences from GenBank. (a) Spatial distribution of SFTSV sequences; (b–d) spatial and temporal distributions of the L, M, and S segments at the country level, respectively; (e–g) spatial and temporal distributions of the L, M, and S segments at the province level, respectively, in China.

Figure 2.

Results of phylogenetic analysis of the L, M, and S segments. The upper panel presents the topology of ML tree, annotated with SH-aLRT and UFboot values for the labeled lineages. The lower panel displays the panoramic view of the ML trees. The outer layers, from left to right, represent the country of origin, the province of China, and the pairwise sequence distance.

Figure 3.

Mean within- and between-lineage distances for L, M, and S segments.

Figure 4.

Spatiotemporal distribution of lineages across L, M, and S segments.

Figure 5.

The phylodynamics of SFTSV. (a) The MCC trees of the L, M, and S segments, respectively. The colors correspond to the probable geographic locations. The circle size indicates the posterior of lineages. For the key nodes, the median estimated TMRCAs of lineages are shown; (b) transmission network of the L segment inferred from the MCC tree. The arrows indicate directionality, and their thickness indicates the transition frequency. Node size is scaled by betweenness centrality values, and a higher value reflects the importance of the node as a hub for the traffic of the pathogen. The colors are randomly assigned. (c) The past population dynamics visualized using the Skygrid model. The shaded portion is the 95% Bayesian credibility interval, and the solid line is the posterior median.

Figure 6.

The positive selection sites and domain structures of RdRp (PDB 6Y6K) (a) and Gn–Gc (PDB 7X6U) (b).