Molecular Evolution and Spatial Transmission of Severe Fever with Thrombocytopenia Syndrome Virus Based on Complete Genome Sequences

Abstract

Severe fever with thrombocytopenia syndrome virus (SFTSV) was a novel tick-borne bunyavirus that caused hemorrhagic fever with a high fatality rate in East Asia. In this study we analyzed the complete genome sequences of 122 SFTSV strains to determine the phylogeny, evolution and reassortment of the virus. We revealed that the evolutionary rate of three genome segments were different, with highest in the S segment and lowest in the L segment. The SFTSV strains were phylogenetically classified into 5 lineages (A, B, C, D and E) with each genome segment. SFTSV strains from China were classified in all 5 lineages, strains from South Korea were classified into 3 lineages (A, D, and E), and all strains from Japan were classified in only linage E. Using the average evolutionary rate of the three genome segments, we found that the extant SFTSV originated 20-87 years ago in the Dabie Mountain area in central China. The viruses were then transmitted to other areas of China, Japan and South Korea. We also found that six SFTSV strains were reassortants. Selection pressure analysis suggested that SFTSV was under purifying selection according to the four genes (RNA-dependent RNA polymerase, glycoprotein, nucleocapsid protein, non-structural protein), and two sites (37, 1033) of glycoproteins were identified as being under strong positive selection. We concluded that SFTSV originated in central China and spread to other places recently and the virus was under purifying selection with high frequency of reassortment.

Fig 1. Phylogenetic analysis of the whole segment sequences of L, M, and S segments of 122 SFTSV strains.

The maximum likelihood trees were constructed by using MEGA 5.02 software (http://www.megasoftware.net/). SFTSV was classified into 5 lineages labeled as A, B, C, D, and E by each genome segment. GenBank accession number and strain name were labeled on each branch. Bootstrap values ≧70 were labeled at nodes. Scale bar represented nucleotide substitutions per site.

Fig 2. Posterior mean and 95% HPDs of the substitution rates estimated from the actual data sets and the 5 tip-date randomizations for the each data set.

Substitution rates on the left for each data set were estimated from the actual data sets. Substitution rates on the right for each data set were estimated from the randomized data sets. The mean rates estimated for the data sets were significantly different from those estimated from the randomized data sets.

Fig 3. Time-scaled Bayesian MCC phylogenetic tree based on concatenated SFTSV complete genome sequences.

Tree nodes were annotated with posterior probability values (right), estimated median dates of time to most recent common ancestor (TMRCA) and 95% confidence interval of TMRCA (above). Lineages (A, B, C, D and E) were marked with different colors. SFTSV strain names were labeled on each branch. Horizontal axis indicated time in years.