Novel SFTSV Phylogeny Reveals New Reassortment Events and Migration Routes

Abstract

Severe fever with thrombocytopenia syndrome virus (SFTSV), the causative agent of a febrile human disease, was first identified from central and eastern provinces in China, and later in Japan and South Korea. Hubei Province is one of the major SFTS epidemic areas in the central part of China. This study reported the isolation of 11 new SFTSV strains from patients in Hubei Province collected in 2017. Extensive phylogenetic analyses were conducted based on the complete coding sequences of SFTSV segments including the new strains. It was suggested that five different SFTSV genotypes were circulating in Hubei, and 15 reassortment patterns and migration pathways correlated with each genotype were identified, which was more than previously recognized. Hubei Province was more involved in the evolutionary events of SFTSV than that previously thought in which the evolutionary events of SFTSV were reported to be independent from those in other epidemic regions. Further divergence of SFTSV strains was suggested by pairwise comparison of SFTSV sequences from each genotype and sequence identity normalized to representative strain in genotype C1. Subsequently, amino acid variations specific for genotype(s), strain(s), or cluster(s) were inspected, which may be related to differential biological activity of SFTSV strains/genotypes. In conclusion, we analyzed the current status of SFTSV phylogeny in Hubei Province and discussed the possible events correlated to SFTSV evolution. It provided an in-depth insight into SFTSV evolution, raising concerns for the use of proper SFTSV strains in future studies.

Keywords: Amino acid variations; Genomic reassortment; Genotypes; Severe fever with thrombocytopenia syndrome virus (SFTSV); Virus migration.

Fig. 1

Phylogenetic analysis of SFTSV strains. The ML trees were constructed based on the sequence alignment of L, M, and S segments (A), (B) and (C), respectively. The 11 strains isolated in this study are indicated by bold black dotted lines. Genotypes (C1 to C6 and J1 to J3) are distinguished in branches of different colors. SFTSV strains from China, Japan, and South Korea are labeled in orange, light purple, and cyan, respectively. Strains from the Hubei Province are indicated in red in a different panel.

Fig. 2

Graphical representation of SFTSV reassortment events listed with the potential reassortants. Segments of each genotype are indicated by different colors. The L, M, and S segments are indicated by different line lengths. Reassortants from the Hubei Province are underlined. Reassortants identified by RDP packages are numbered in accordance with the events listed in Supplementary Table S5.

Fig. 3

Migration pathways of the different SFTSV genotypes in China, Japan, and South Korea. Migration pathways of each SFTSV genotype were shown in an enlarged map showing areas including provinces in China, South Korea, and Japan. One-way arrows indicate export or import-only events, and double-sided arrows indicate a virus export and import pathway. Migrations involving the S segment only are shown in green, involving the L and S segments in blue, involving the M and S segments in orange, and involving all three segments in red.

Fig. 4

Comparison of genomic sequence identity of SFTSV strains. A Pairwise sequence comparison of SFTSV strains within the same genotype. The identity range is plotted as a box plot for each genotype. The upper and lower bars represent the maximum and minimum values, respectively. The box shows identities ranging from 25% to 75% of the total values, and the solid line in the middle indicates the median. B Normalized sequence identities of SFTSV strains to the C1 genotype SD4/China/2010 strain, plotted as violin plots. The median and quartile identities are indicated by “(solid dotted lines)” and “(dotted lines)”, respectively.

Fig. 5

Analysis of hotspot sites for amino acid variations in (A) RdRp, (B) GP, and (C) NSs proteins among the indicated genotype. Substitutions are shown in different colors: green for acidic amino acids, purple for alkaline amino acids, red for hydrophilic amino acids, and blue for hydrophobic amino acids.