Molecular genomic characterization of tick- and human-derived severe fever with thrombocytopenia syndrome virus isolates from South Korea

Abstract

BackgroundSevere fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne viral disease caused by the SFTS virus (SFTSV) from Bunyaviridae that is endemic in East Asia. However, the genetic and evolutionary characteristics shared between tick- and human-derived Korean SFTSV strains are still limited.Methodology/Principal findingsIn this study we identify, for the first time, the genome sequence of a tick (Haemaphysalis longicornis)-derived Korean SFTSV strain (designated as KAGWT) and compare this virus with recent human SFTSV isolates to identify the genetic variations and relationships among SFTSV strains. The genome of the KAGWT strain is consistent with the described genome of other members of the genus Phlebovirus with 6,368 nucleotides (nt), 3,378 nt, and 1,746 nt in the Large (L), Medium (M) and Small (S) segments, respectively. Compared with other completely sequenced human-derived Korean SFTSV strains, the KAGWT strain had highest sequence identities at the nucleotide and deduced amino acid level in each segment with the KAGWH3 strain which was isolated from SFTS patient within the same region, although there is one unique amino acid substitution in the Gn protein (A66S). Phylogenetic analyses of complete genome sequences revealed that at least four different genotypes of SFTSV are co-circulating in South Korea, and that the tick- and human-derived Korean SFTSV strains (genotype B) are closely related to one another. Although we could not detect reassortant, which are commonly observed in segmented viruses, further large-scale surveillance and detailed genomic analysis studies are needed to better understand the molecular epidemiology, genetic diversity, and evolution of SFTSV.Conclusions/SignificanceFull-length sequence analysis revealed a clear association between the genetic origins of tick- and human-derived SFTSV strains. While the most prevalent Korean SFTSV is genotype B, at least four different genotypes of SFTSV strains are co-circulating in South Korea. These findings provide information regarding the molecular epidemiology, genetic diversity, and evolution of SFTSV in East Asia.

Genetic and pathogenic diversity of severe fever with thrombocytopenia syndrome virus (SFTSV) in South Korea

“…The finding of high prevalence and mortality rate in the elderly is in agreement with corresponding data from other studies (30). The phy- logenetic tree of 335 SFTSV strains, including 116 strains identified in this study, revealed that most Korean SFTSVs can be classified into the 6 previously identified genotypes (A-F) (19,26), and the B genotype can be subdivided into at least 3 different genotypes (B-1, B-2, and B-3). Further, inconsistent phylogenetic clustering segments suggested that at least 6 genotypes were co-circulating and 9 reassortments among them in South Korea.…”

“…These sequences, as well as all known SFTSV full-length sequences available in GenBank, were subjected to phylogenetic analysis ( Figure 2 and Supplemental Figure 2). The results show that Korean SFTSVs can be roughly classified into A-F genotypes based on the classification method previously used in China and Korea (19,26). The majority of Korean SFTSV isolates (n = 92 of 133, 69.2%) were classified as the B genotype.…”

Structural and functional characterization of the Severe fever with thrombocytopenia syndrome virus L protein

“…Notably, for the sequences of the conserved genome segment termini, particularly the S segment, different sequences have been published. For the S segment these sequences differ in the insertion/deletion of an A at position 9, counted from the 5' terminus, or a U in 460 case of the 3' terminus (47)(48)(49). The S segment RNA including the A at position 9 (denoted as 9A) resulted in much stronger polymerase activity of the L protein compared to the Ssegment promoter lacking the 9A, even though the affinity to the L protein seems to be comparable between the two S segment promoters ( Supplementary Figures S5 and S9).…”

Pathophysiology of severe fever with thrombocytopenia syndrome and development of specific antiviral therapy

“…The evidence of tick bites in patients with SFTS based on the detection of ticks on the skin surface and/or detection of possible tick-bite scars was not shown in one half of the SFTS patients in Japan [5]. Furthermore, H. longicornis and A. testudinarium play roles in transmitting SFTSV to humans in Japan, whereas in PR China and South Korea, the main vector involved in transmitting the virus to humans might be H. longicornis [11,13,14].…”

“…The SFTSV genome was also detected in the tick species Amblyomma (A.) testudinarium in South Korea and Japan [5,11,12]. The seasonality of SFTS is year-round, but most patients in Japan become ill between spring and autumn.…”