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. 2023 Sep 15;17(9):e0011630.
doi: 10.1371/journal.pntd.0011630. eCollection 2023 Sep.

Genome-informed investigation of the molecular evolution and genetic reassortment of severe fever with thrombocytopenia syndrome virus

Kyuyoung Lee  1 , Jong Hyeon Seok  1 , Hyunbeen Kim  1 , Sejik Park  1 , Sohyun Lee  1 , Joon-Yong Bae  1 , Kyeongseok Jeon  2 , Jun-Gu Kang  3 , Jeong Rae Yoo  4 , Sang Taek Heo  4 , Nam-Hyuk Cho  2 , Keun Hwa Lee  5 , Kisoon Kim  1   6 , Man-Seong Park  1   6   7 , Jin Il Kim  1   6   7
Affiliations

Genome-informed investigation of the molecular evolution and genetic reassortment of severe fever with thrombocytopenia syndrome virus

Kyuyoung Lee et al. PLoS Negl Trop Dis. .

Abstract

Background: Severe fever with thrombocytopenia syndrome virus (SFTSV) is a viral pathogen causing significant clinical signs from mild fever with thrombocytopenia to severe hemorrhages. World Health Organization has paid special attention to the dramatic increase in human SFTS cases in China, Japan, and South Korea since the 2010s. The present study investigated the molecular evolution and genetic reassortment of SFTSVs using complete genomic sequences.

Methods/principal finding: We collected the complete genome sequences of SFTSVs globally isolated until 2019 (L segment, n = 307; M segment, n = 326; and S segment, n = 564) and evaluated the evolutionary profiles of SFTSVs based on phylogenetic and molecular selection pressure analyses. By employing a time-scaled Bayesian inference method, we found the geographical heterogeneity of dominant SFTSV genotypes in China, Japan, and South Korea around several centuries before and locally spread by tick-born spillover with infrequent long-distance transmission. Purifying selection predominated the molecular evolution of SFTSVs with limited gene reassortment and fixed substitution, but almost all three gene segments appeared to harbor at least one amino acid residue under positive selection. Specifically, the nonstructural protein and glycoprotein (Gn/Gc) genes were preferential selective targets, and the Gn region retained the highest number of positively selected residues.

Conclusion/significance: Here, the large-scale genomic analyses of SFTSVs improved prior knowledge of how this virus emerged and evolved in China, Japan, and South Korea. Our results highlight the importance of SFTSV surveillance in both human and non-human reservoirs at the molecular level to fight against fatal human infection with the virus.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Summary of incidence and case fatality rate (CFR) of human SFTSV infection from 2013 to 2021.
Annual incidence (Dotted and triangle) and CFR (Line and circle) of the SFTSV in China (Green), Japan (Black), and South Korea (Red) from 2013 to 2021. The plot was reconstructed from the statistics of national surveillance reports in China [15], Japan [16], and South Korea [17].
Fig 2
Fig 2. Phylogenetic relationships of SFTSV.
The maximum clade credibility tree of the (A) Long (L), (B) Medium (M), (C) Short (S) gene segments was reconstructed using the Bayesian evolutionary interference method. The brackets in the x-axis display the genotype classification by Fu et al (2016). The phylogenetic branches with specific countries were color labeled black (China), red (Japan), and blue (South Korea), respectively.
Fig 3
Fig 3. Evolutionary rate and the time of most recent common ancestor (tMRCA) of three gene segments in SFTSV by three countries.
(A) The Evolutionary rate and (B) tMRCA of Long (L), Medium (M), Short (S) gene segments were summarized by median and 95% HPD.
Fig 4
Fig 4. Reassortment between pairs of three gene segments in SFTSV.
(A) Reassortment of the L and M gene, (B) the L and S gene (C) the M and S gene segments. The red line between phylogeny depicted gene reassortment between two genes. The brackets in the y-axis display the genotype classification by Fu et al (2016).
See this image and copyright information in PMC

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