A comprehensive study of the Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) in East Asia, spanning the years 2017 to 2023, has uncovered crucial details about the virus’s origins and migratory patterns. The research, which focused on the molecular evolution and geographic spread of SFTSV, provides key insights into how the virus has disseminated across the region, impacting public health and disease control strategies.

SFTSV,a tick-borne virus identified in the 21st century,is the causative agent of severe fever with thrombocytopenia syndrome. This disease is characterized by high morbidity and mortality rates, making it a meaningful public health concern across East Asia. The recent study underscores the importance of understanding the spatial and temporal dynamics of SFTSV migration to implement effective prevention and control measures.

Researchers meticulously collected and analyzed SFTSV strains from East asian countries, utilizing data available in genbank from 2017 to 2023. The analysis revealed that SFTSV can be categorized into five distinct genotypes: A, B, C, D, and E. This classification is crucial for tracking the virus’s evolution and spread. The study also identified a notable number of recombination and reassortment events,with 24 recombination events and 15 reassortment events detected.This is a higher number than previously observed in similar studies, highlighting the virus’s dynamic genetic nature.

The study indicates that SFTSV first diverged around 1785, marking the beginning of its evolutionary journey. Researchers categorized the virus’s migration into two distinct periods, identifying the centers of spread and migration routes for each phase. This detailed temporal analysis provides a clearer picture of how the virus has evolved and spread over time, offering valuable insights for public health officials.

One of the key findings of the study points to the significant role of migratory birds in the initial stages of virus transmission. According to the research, the eastern migration routes of these birds served as a primary conduit for the dispersal of the virus across the sea. In subsequent phases of transmission, both eastern and central migratory routes played similarly pivotal roles.

The research suggests that Japan was the first region where the virus originated and became endemic. From there, the virus spread widely among countries in East Asia. This conclusion challenges previous hypotheses about the origin and spread of SFTSV, providing a new outlook on the virus’s early history.

Researchers emphasized the significance of their findings, stating that elucidating the spatial and temporal characteristics of SFTSV migration is crucial for preventing and controlling the disease. By understanding how the virus moves and evolves, public health officials can develop more targeted and effective interventions.

The research methodology involved a detailed analysis of SFTSV sequences obtained from GenBank. The dataset included 1,645 sequences, with 485 strains exhibiting complete L, M, S segments. The sequences were analyzed using the ClustalW method in bioedit for sequence alignment, and phylogenetic trees were constructed using the maximum likelihood (ML) method in IQtree-2.3.1. This rigorous approach ensured the accuracy and reliability of the study’s findings.

To reduce redundancy and prevent over-portrayal of genomic data, the researchers removed sequences with greater than 99.9% similarity, resulting in a refined dataset of 1,253 sequences for phylogenetic analysis. This step was crucial for ensuring the robustness of the analysis and the validity of the conclusions drawn.

The study’s findings build upon previous research, which had varying conclusions regarding the origin and migratory pathways of SFTSV. Some studies suggested that SFTSV originated in central China, while others pointed to Zhejiang Province, Korea, or Japan as potential sources. The current research provides a more definitive answer, identifying Japan as the origin point.

The researchers highlight the importance of considering the role of migratory birds in the spread of SFTSV. The coincidence between migratory bird routes and the virus’s migration patterns strongly suggests that these birds play a significant role in the transoceanic spread of the virus. This finding has significant implications for future research and public health interventions.

The study’s authors suggest that future research should focus on further investigating the specific mechanisms by which migratory birds facilitate virus transmission.This could lead to the development of more effective prevention and control strategies, ultimately reducing the impact of SFTSV on public health.

the research was supported by the Special Key Project of biosafety Technologies and the Natural Science Foundation of Shandong Province. The funders had no role in the study design, data collection and analysis, decision to publish, or readiness of the manuscript, ensuring the objectivity and integrity of the research.

Introduction

A comprehensive phylogeographic analysis of the Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) has shed light on the virus’s evolutionary dynamics and transmission pathways across Asia. The study, encompassing data from Japan, Korea, Thailand, and nine provinces in China, identifies key reassortment events and genetic relationships, offering valuable insights into the virus’s spread and adaptation.

Methodology: Unraveling the Viral Code

The research employed a rigorous methodology to analyse the genetic makeup of SFTSV. the process began with sequence alignment,utilizing MAFFT v7.475, to ensure accurate comparisons of the viral genomes. Phylogenetic trees, crucial for understanding evolutionary relationships, were constructed using the Maximum Likelihood (ML) method implemented in IQ-TREE v2.0.3. This involved selecting the most appropriate nucleotide substitution model, persistent by ModelFinder, to accurately reflect the evolutionary processes at play.

To ensure the robustness of the phylogenetic analysis,the team used specific parameters for each segment of the virus: F+I+R3 for the L segment,GTR+F+I+R4 for the M segment,and TVMe+R for the S segment.The plausibility of the phylogenetic tree structure was evaluated through the submission of the Bootstrap method, with 1,000 ultrafast bootstrap replicates.

The “ape” package in R 4.1.0 was utilized to conduct a comparative analysis of the topological structures of the phylogenetic trees of the L, M, and S segments, and the classification of genotypes was carried out based on the results of the comparative analysis. Since there is no standardized method for SFTSV genotype classification, the phylogenetic tree of the S segment was used as a reference, and the branches from top to bottom were named as genotypes A – E. moreover,the intra-group and inter-group genetic distances of each virus genotype were calculated by using MEGA 11.0.

Recombination and Reassortment Analysis: Identifying Genetic Mixing

The study also delved into the phenomenon of reassortment, where different segments of the virus genome are mixed and matched.Based on the genotype data obtained in the “phylogenetic analysis” section, the three sequences of the same virus strain were compared. If the genotypes inferred from the L, M and S gene segments are different, it is considered to be a potential reassortment strain.

To further investigate the genetic dynamics of SFTSV, the researchers analyzed recombination events within the viral genome using the Recombination detection Program v4.101 (RDP4) package. The occurrence of recombination breakpoints at the terminal position of a segment is defined as a recombination event. Following a comparison of the three segments in Fasta format, the data were imported into RDP4 using the seven available methods: RDP, 3Seq, GENECONV, SiScan, Chimaera, bootscan, and Maxchi. A recombination event was deemed authentic if it was identified by a minimum of three of the seven analytical techniques, with a p-value threshold of 0.05. The recombinant strain’s associations with the major and minor parent were then observed. The aforementioned analytical techniques were integrated to ascertain the recombination events.

A groundbreaking phylogeographic analysis of the Severe Fever with Thrombocytopenia Syndrome virus (SFTSV) has illuminated its complex evolutionary history and migration patterns across Asia. The study, which examined full-genome sequences from Japan, Korea, Thailand, and nine provinces in China, estimates the virus’s time of origin to be around 1785. Researchers meticulously analyzed viral migration by comparing the sequences of the S segments of SFTSV, revealing intricate transmission pathways involving Japan, South Korea, and mainland China. These findings underscore the significant genetic diversity of SFTSV and the mechanisms driving its evolution, including reassortment and recombination, offering crucial insights for public health strategies.

The research provides a detailed examination of SFTSV’s genetic structure, a virus known for causing severe illness in humans. By scrutinizing the virus’s L, M, and S segments, scientists have reconstructed its evolutionary journey and identified key factors contributing to its diversification. The study emphasizes the importance of understanding these evolutionary processes to better predict and manage future outbreaks of this potentially deadly virus.

Genetic Diversity and phylogenetic Analysis

The comprehensive analysis included 485 SFTSV strains with full-length genome sequences. These strains originated from Japan, Korea, Thailand, and nine provinces in China: Liaoning, Beijing, Shandong, Henan, Zhejiang, Jiangxi, Hubei, Anhui, and Chinese Taiwan, as indicated by strain names in GenBank and related reports. researchers employed the Maximum likelihood (ML) method to construct three phylogenetic trees based on full-length S,M,and L segment sequences. While the evolutionary positions of these trees differed slightly across the segments, they exhibited a comparable topology, with the viral strains distinctly clustered into five branches, designated as A, B, C, D, and E.

A notable clustering of strains was observed, predominantly originating from Japan, Thailand, Korea, and Zhejiang Province, China. These strains exhibited a predominant distribution within genotypes A and D. The findings indicated that the strains from Zhejiang Province were more closely related to those from Japan, Korea, and Thailand in terms of evolutionary history.

Genotype A is mostly from China, such as Henan Province, with strains also found in japan and Thailand. genotype B exhibited disparate behavior across the three trees, comprising strains from Japan and Chinese Taiwan in the S-tree, strains from Japan and Hubei Province only in the M-tree, and strains from Hubei Province only in the L-tree. It is hypothesized that the primary cause of this phenomenon is the presence of incomplete gene sequences, and the secondary cause is the occurrence of reassortment events.Genotype C encompassed strains originating from Shandong Province and multiple other inland provinces within China. Genotype D was predominantly represented by the Japanese, Korean, Thailand, and Zhejiang Province strains. Genotype E represented the largest branch and encompasses the majority of strains originating from China’s inland provinces.

Reassortment Events and Genetic Exchange

The study revealed that the majority of SFTSV strains (96.9%, 470/485) showed consistent genotype classification among the three genomic segments. However,15 strains (3.1%, 15/485) showed inconsistent genotype results, suggesting reassortment. Of these 15 strains, 12 originated from central China (Henan, Hubei, and Jiangxi Provinces), two were from Japan, and the remaining one lacked geographical location information.

A total of 15 reassorted strains were classified into 10 types. The strains were named in the L-M-S order according to the genotypes of the three segments in their respective phylogenetic trees. These included AEE (with 3 sequences), AAB (with 2 sequences), DAD (with 2 sequences), EAA (with 2 sequences), AAC, BBE, CEE, ECC, EEC and a unique reassortment genotype (CGC, where G represents unassigned).

Recombination Analysis and Hotspots

Researchers analyzed homologous recombination in all sequences of the S, M, and L segments separately using RDP. The study indicated that regions exhibiting the highest levels of recombination activity were widely distributed across both L and M segments. The S segment, though, showed less recombination activity, suggesting a more stable internal structure.

In the S segment,only three sequences showed homologous recombination,all originating from inland China. This suggests that the S segment relies less on recombination for introducing large-scale sequence variations during evolution.

A total of nine sequences underwent homologous recombination in the M segments analyzed, all from inland china, with most recombination occurring in genotype C. One recombinant sequence, M2 (OQ388971) from hubei Province, was typed the same as its minor parental sequences, which included a Thailand strain. Another sequence, M3 (OQ388989), also from Hubei Province, had a Japanese virus sequence in its minor parental sequence. M5 (OM452787) from Henan Province, had Korean viral sequences in its major parental sequences, while its minor parental sequences were all from mainland China. M8 (OM452726), also from Henan Province, had Japanese viral sequences in its minor parental sequences.

Twelve sequences underwent homologous recombination in the L segments. Only one sequence (L7:MT413432) originated from coastal China (Shandong Province), with a tick host and classified as type C as its major parental sequences. Its minor parental sequences demonstrated the involvement of Japan,Korea,and Thailand,and was classified as type D. Among the strains from inland, L4 (0M453367) from Henan province, exhibited greater specificity, with its major parental host being ticks and its minor parental strain derived from mainland China and Thailand.

Time of Origin and Migration Pathways

Using the S segment for analysis due to its relatively stable internal structure, researchers constructed an MCC tree using 498 full-length S segments. The analysis supported a TMRCA (Time to most Recent Common Ancestor) of 1785 (95% HPD = 1625 to 1897). Genotype C differentiated around 1898 (95% HPD = 1841 to 1937), genotype D around 1868 (95% HPD = 1812 to 1917), genotype E around 1891 (95% HPD = 1840 to 1934), and genotypes A and B around 1932 (95% HPD = 1888 to 1964). Despite emerging later, genotype E is the most prevalent in china.

The study’s visualization of SFTSV transmission paths revealed a shift in the virus’s spread over time.Prior to 1980, Japan served as the primary source of transmission, with the virus spreading to South Korea, Chinese Taiwan, and Henan Province. After 1980, the transmission became more diversified, with Japan, Henan, and Hubei Provinces acting as transmission centers, spreading the virus to surrounding provinces in mainland China.

Implications and Future research

this phylogeographic analysis of SFTSV provides a comprehensive overview of the virus’s genetic diversity and evolutionary patterns across Asia.The identification of reassortment events and the mapping of transmission pathways offer crucial insights for understanding the virus’s spread and adaptation. These findings have significant implications for public health efforts aimed at controlling and preventing SFTSV infections.

Genetic Recombination and Viral Evolution

the study focused on the L, M, and S segments of SFTSV, revealing that the highest number of recombination events occured in the L segment, while the lowest was observed in the S segment. A notable finding was that all recombinant sequences originated from China. Though, the major or minor parental sequences of some of these sequences were traced back to Japan and Korea.

Researchers identified ticks as hosts of some recombinant sequences and their parents, suggesting that recombination of SFTSV may occur in both humans and ticks. The data predominantly came from human patients and ticks, with fewer strains derived from other animals. This limitation makes it impossible to definitively rule out the possibility of recombination events of SFTSV in other animal species.

this phenomenon indicates that SFTSV has migrated over considerable distances between China, Japan, and Korea. The recombination and reassortment of virus segments in multiple regions contribute to the expansion of genetic diversity and the accelerated evolution of SFTSV.

Temporal and Spatial Dynamics

Bayesian analysis indicated that the time to the most recent common ancestor (TMRCA) for all sampled SFTSV strains was 1785. The analysis predicts that genotype D is the earliest to differentiate, while genotypes A and B represent the most recent, with differentiation occurring around 1932.

These findings contrast with previous suggestions that the virus originated 50–150 years ago. The researchers address this discrepancy,stating,Several scholars have previously suggested that the virus originated 50–150 years ago,and the data they used were generally from before 2015,while the data we used were from 2017-2023. These data are more accurate and have a wider range of hosts and geographical sources. Thus, we believe that the reason for this discrepancy is mainly due to the bias in the gene sequence data.

Geographic Migration and Transmission Pathways

The geographic migration analysis delineated two distinct phases in the dissemination of SFTSV. The initial period, from 1785 to 1980, saw the virus transmitted from Japan to China. The subsequent period, from 1980 to 2023, marked the extensive proliferation of the virus across East Asia.

In the initial phase, the transmission pathway was relatively homogeneous, with Japan serving as the primary source. However, the subsequent phase showed a notable diversification, with the epicenter shifting to three distinct regions: Japan, Henan, and Hubei Provinces.

The study suggests that SFTSV first originated in Japan and subsequently spread to Korea, Chinese Taiwan, and central China. From there,it is believed to have spread from central China to neighboring regions. The natural barrier of the ocean between countries necessitates indirect transmission through specific hosts.

Ticks serve as key hosts and vectors, transmitting SFTSV to other animals, including mammals, land birds, and seabirds, primarily through their bites. The researchers posit that international travel and bird migration are significant conduits for SFTSV transmission.

Role of Migratory Birds

The migratory routes of waterbirds in China’s wetlands are primarily classified into three distinct routes: the eastern, central, and western. The Eastern Migratory Route is a significant component of the East Asian–Australasian Flyway.

The migratory patterns of wetland waterbirds breeding in Russia, Japan, the Korean Peninsula, and northeastern and eastern North China indicate a north-south trajectory, with the majority traversing the eastern coast of China during the spring and fall seasons. In spring, northward migrating birds arrive in Chinese Taiwan and divide into two branches, one spreading along the Chinese mainland or moving northward along the east coast, and the other going to Japan or continuing northward via the Ryukyu Islands.

Wetland waterbirds migrating north along the east coast of mainland China are divided into two northward migration routes at the mouth of the Yangtze River. One goes through Jiangsu and Shandong provinces to the northeast and Russia,while the other crosses the sea to the Korean Peninsula or Japan. In the fall, its southern migration route is roughly similar to the northern route in the spring.

The Central migration Route is a migration route within China where migratory birds fly south along the Yellow River Basin, Luliang Mountains, and Taihang Mountains in the fall to winter in central China or further south.

The findings revealed that four transmission routes—Japan-Korea, japan-Chinese Taiwan, Japan-inland China, and Korea-inland China—exhibited a high degree of overlap with the East Asia-Australia migration routes. The virus-endemic regions of inland provinces in China,including Henan,Hubei,Jiangxi,Anhui,and Beijing,demonstrated a markedly high degree of overlap with the Central China migration routes.

The eastern migratory route was of significant importance during the initial stages of virus transmission, acting as a principal conduit for the virus’s dispersal across the sea. The eastern and central migratory routes were similarly instrumental in the subsequent phases of virus transmission.

It is indeed postulated that migratory birds play a pivotal role in the dissemination of SFTSV, explaining the observed spread in coastal regions across East Asia. The impact of international travel, import and export trade, and other factors cannot be discounted.

Pioneering Bird Research

The Cornell Lab of Ornithology is renowned for its cutting-edge research that delves into various aspects of avian life. From studying bird behavior and ecology to investigating migration patterns and population dynamics, the lab’s research initiatives provide invaluable insights into the complex world of birds. This research informs conservation strategies and helps to address the challenges facing bird populations worldwide.

Understanding bird migration patterns, such as, is crucial not only for conservation but also for understanding the spread of diseases. As highlighted in a 2022 study published in *Emerging Infectious Diseases*, migratory birds can play a role in the transoceanic spread of viruses. This underscores the importance of the Cornell Lab’s research in a broader context.

Commitment to Conservation

Conservation is at the heart of the Cornell Lab of Ornithology’s mission. The lab actively engages in projects aimed at protecting bird habitats, mitigating threats to bird populations, and promoting enduring practices. By collaborating with local communities, government agencies, and other organizations, the lab works to ensure the long-term survival of birds and their ecosystems.

Protecting bird habitats involves a multifaceted approach, including habitat restoration, conservation easements, and advocating for policies that protect critical bird areas. The Cornell Lab’s collaborative approach ensures that conservation efforts are both effective and sustainable.

Education and Outreach Programs

The Cornell Lab of Ornithology is committed to educating the public about birds and their importance to the surroundings. Through a variety of educational programs, including online courses, workshops, and citizen science projects, the lab empowers individuals to become actively involved in bird conservation. These programs foster a greater appreciation for birds and inspire action to protect them.

Citizen science projects, such as eBird, allow everyday individuals to contribute valuable data to bird research and conservation. By engaging the public, the Cornell Lab fosters a sense of stewardship and empowers individuals to make a difference.

Asian Longhorned Ticks and the Rapid Spread of SFTS Virus

A study by Zhang X, Zhao C, Cheng C, Zhang G, yu T, Lawrence K, et al., published in *Emerging Infectious Diseases* in 2022, sheds light on the rapid spread of severe Fever with Thrombocytopenia Syndrome (SFTS) Virus by parthenogenetic Asian Longhorned Ticks. The research, detailed in the journal’s February 2022 issue, highlights the potential for these ticks to accelerate the transmission of the virus.

The study, titled Rapid Spread of Severe Fever with Thrombocytopenia Syndrome Virus by Parthenogenetic Asian Longhorned Ticks, appeared in *Emerg Infect Dis*. 2022;28(2):363–72. the research article’s PMID is 35075994, and its PMCID is PMC8798674.

This research underscores the interconnectedness of ecosystems and the importance of understanding how various factors, including invasive species like the Asian Longhorned Tick, can impact public health.the Cornell Lab’s broader research into avian ecology and migration patterns provides valuable context for understanding the potential spread of such diseases.

SFTSV Origins and Migration: A Complex Puzzle

Recent research provides a more comprehensive understanding of the Severe Fever with Thrombocytopenia syndrome Virus (SFTSV), a tick-borne virus prevalent in East Asia.While previous studies suggested various origins, including central China, Zhejiang province, and Korea, these articles strongly support Japan as the initial location where SFTSV became endemic, around 1785.The virus subsequently spread throughout East Asia.

A significant finding emphasizes the pivotal role of migratory bird routes, notably eastern routes initially and both eastern and central routes later, in the transoceanic spread of SFTSV. Further research is needed to elucidate the specific transmission mechanisms.

The migration of SFTSV is characterized by two distinct periods, each with identified centers of spread and respective routes.

Genetic Evolution and Diversity of SFTSV

the SFTSV virus is categorized into five genotypes (A, B, C, D, and E), with variations in geographical distribution. Genotype A is prevalent in China (Henan), with strains also found in Japan and Thailand. Genotype D is predominantly found in Japan, Korea, Thailand, and Zhejiang province. Genotype E is the most widespread across inland China.

A remarkably high number of recombination (24 events in one study) and reassortment (15 events in one study, 15 in another) events were detected, considerably higher than in previous research, highlighting the dynamic genetic evolution of SFTSV. These events predominantly occur in the M and L segments, with the S segment exhibiting greater stability.

A notable percentage of SFTSV strains (3.1% in one study) showed inconsistent genotype classifications across the L, M, and S segments, providing further evidence of reassortment. The reassortments frequently enough involve strains from central China, and less frequently, Japan and Korea.

Methodology Used in SFTSV Research

All three studies used phylogenetic analysis (maximum likelihood and Bayesian methods) and employed different software (IQ-tree, MAFFT, RDP4, BEAST, SpreaD3) to analyze SFTSV sequences from GenBank, focusing on the L, M, and S segments of the viral genome. Data cleaning to remove redundant sequences was performed to ensure robust analysis.