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Background Whole-genome sequencing plays a critical role in the genomic epidemiology intended to improve understanding the spread of emerging viruses. Dabie bandavirus, causing severe fever with thrombocytopenia syndrome (SFTS), is a zoonotic tick-borne virus that poses a significant public health threat. We aimed to evaluate a novel amplicon-based nanopore sequencing tool to obtain whole-genome sequences of Dabie bandavirus, also known as SFTS virus (SFTSV), and investigate the molecular prevalence in wild ticks, Republic of Korea (ROK). Principal findings A total of 6,593 ticks were collected from Gyeonggi and Gangwon Provinces, ROK in 2019 and 2020. Quantitative polymerase chain reaction revealed the presence of SFSTV RNA in three Haemaphysalis longicornis ticks. Two SFTSV strains were isolated from H. longicornis captured from Pocheon and Cheorwon. Multiplex polymerase chain reaction-based nanopore sequencing provided nearly full-length tripartite genome sequences of SFTSV within one hour running. Phylogenetic and reassortment analyses were performed to infer evolutionary relationships among SFTSVs. Phylogenetic analysis grouped SFTSV Hl19-31-4 and Hl19-31-13 from Pocheon with sub-genotype B-1 in all segments. SFTSV Hl20-8 was found to be a genomic organization compatible with B-1 (for L segment) and B-2 (for M and S segments) sub-genotypes, indicating a natural reassortment between sub-genotypes. Conclusion/Significance Amplicon-based next-generation sequencing is a robust tool for whole-genome sequencing of SFTSV using the nanopore platform. The molecular prevalence and geographical distribution of SFTSV enhanced the phylogeographic map at high resolution for sophisticated prevention of emerging SFTS in endemic areas. Our findings provide important insights into the rapid whole-genome sequencing and genetic diversity for the genome-based diagnosis of SFTSV in the endemic outbreak.

With global warming and lush forest change, vector-borne infections are expected to increase in the number and diversity of agents. Since the first report of severe fever with thrombocytopenia syndrome (SFTS) in 2013, the number of reported cases has increased annually in South Korea. However, although tick-borne encephalitis virus (TBEV) was detected from ticks and wild rodents, there is no human TBE case report in South Korea. This study aimed to determine the seroprevalence of TBEV and SFTS virus (SFTSV) among forest and field workers in South Korea. From January 2017 to August 2018, a total 583 sera were obtained from the forest and field workers in South Korea. IgG enzyme-linked immunosorbent assay (ELISA) and neutralization assay were conducted for TBEV, and indirect immunofluorescence assay (IFA) and neutralization assay were performed for SFTSV. Seroprevalence of TBEV was 0.9% (5/583) by IgG ELISA, and 0.3% (2/583) by neutralization assay. Neutralizing antibody against TBEV was detected in a forest worker in Jeju (1:113) and Hongcheon (1:10). Only 1 (0.2%) forest worker in Yeongju was seropositive for SFTSV by IFA (1:2,048) and neutralizing antibody was detected also. In conclusion, this study shows that it is necessary to raise the awareness of physicians about TBEV infection and to make efforts to survey and diagnose vector-borne diseases in South Korea., Author summary With global warming and lush forest change, vector-borne infections are expected to increase in the number and diversity of agents. Since the first report of severe fever with thrombocytopenia syndrome (SFTS) in 2013, the number of reported cases has increased annually in South Korea. However, although tick-borne encephalitis virus (TBEV) was detected from ticks and wild rodents, there is no human TBE case report in South Korea. This study aimed to determine the seroprevalence of TBEV and SFTS virus (SFTSV) among forest and field workers in South Korea. Among 583 forest/field workers, the seroprevalence of neutralizing antibodies against TBEV and SFTSV were 0.3% (2/583) and 0.2% (1/583), respectively. This study shows that it is necessary to raise the awareness of physicians about TBEV infection and to make efforts to survey and diagnose vector-borne diseases in South Korea.

Severe fever with thrombocytopenia syndrome virus (SFTSV) infection is commonly reported in countries of Northeast Asia including China, Japan and South Korea. The majority of the SFTS patients are elderly and the average fatality rate is more than 10%. A rapid and sensitive diagnostic method to monitor and prevent SFTSV transmission remains an urgent clinical challenge. In this study, we developed a molecular diagnostic technique for detection of SFTSV using the CRISPR-Cas12a system combined with reverse transcription recombinase polymerase amplification (RT-RPA). Using this method, we successfully diagnosed SFTSV infections with the reaction time of 50 min from blood plasma without cross-reactivity to other viruses, supporting its application for rapid and sensitive diagnosis of SFTS.

Background Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease with high case fatality rate. Unfortunately, no vaccine or antiviral specifically targeting SFTS virus (SFTSV) are available for the time being. Our objective was to investigate the association between clinical laboratory parameters and fatality of SFTS patients. Methods The systematic review was conducted in accordance with The Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. We searched (from inception to 24th February 2022) Web of Science, PubMed, National Knowledge Infrastructure databases and Wan Fang Data for relevant researchers on SFTS. Studies were eligible if they reported on laboratory parameters of SFTS patients and were stratified by clinical outcomes. A modified version of Newcastle-Ottawa scale was used to evaluate the quality of included studies. Standardized mean difference (SMD) was used to evaluate the association between laboratory parameters and outcomes. The between-study heterogeneity was evaluated quantitatively by standard Chi-square and the index of heterogeneity (I2). Heterogeneity was explored by subgroup and sensitivity analyses, and univariable meta-regression. Publication bias was determined using funnel plots and Egger’s test. Results We identified 34 relevant studies, with over 3300 participants across three countries. The following factors were strongly (SMD>1 or SMDP Conclusions/significance The abnormal levels of viral load, PLT, coagulation function and liver function, significantly increase the risk of SFTS mortality, suggesting that SFTS patients with above symptoms call for special concern.

Background This study aimed to explore whether the transmission routes of severe fever with thrombocytopenia syndrome (SFTS) will be affected by tick density and meteorological factors, and to explore the factors that affect the transmission of SFTS. We used the transmission dynamics model to calculate the transmission rate coefficients of different transmission routes of SFTS, and used the generalized additive model to uncover how meteorological factors and tick density affect the spread of SFTS. Methods In this study, the time-varying infection rate coefficients of different transmission routes of SFTS in Jiangsu Province from 2017 to 2020 were calculated based on the previous multi-population multi-route dynamic model (MMDM) of SFTS. The changes in transmission routes were summarized by collecting questionnaires from 537 SFTS cases in 2018–2020 in Jiangsu Province. The incidence rate of SFTS and the infection rate coefficients of different transmission routes were dependent variables, and month, meteorological factors and tick density were independent variables to establish a generalized additive model (GAM). The optimal GAM was selected using the generalized cross-validation score (GCV), and the model was validated by the 2016 data of Zhejiang Province and 2020 data of Jiangsu Province. The validated GAMs were used to predict the incidence and infection rate coefficients of SFTS in Jiangsu province in 2021, and also to predict the effect of extreme weather on SFTS. Results The number and proportion of infections by different transmission routes for each year and found that tick-to-human and human-to-human infections decreased yearly, but infections through animal and environmental transmission were gradually increasing. MMDM fitted well with the three-year SFTS incidence data (PR2 = 96%). Reported incidence increased when sunshine duration was higher than 11 h per day and decreased when temperatures were too high (>28°C). Sunshine duration and temperature had the greatest effect on transmission from host animals to humans. The effect of extreme weather conditions on SFTS was short-term, but there was no effect on SFTS after high temperature and sunshine hours. Conclusions Different factors affect the infection rate coefficients of different transmission routes. Sunshine duration, relative humidity, temperature and tick density are important factors affecting the occurrence of SFTS. Hurricanes reduce the incidence of SFTS in the short term, but have little effect in the long term. The most effective intervention to reduce the incidence of SFTS is to reduce population exposure to high-risk environments.

Severe fever with thrombocytopenia syndrome (SFTS) is a bunyavirus infection with high mortality. Favipiravir has shown effectiveness in preventing and treating SFTS virus (SFTSV) infection in animal models. A multicenter non-randomized, uncontrolled single arm trial was conducted to collect data on the safety and the effectiveness of favipiravir in treatment of SFTS patients. All participants received favipiravir orally (first-day loading dose of 1800 mg twice a day followed by 800 mg twice a day for 7–14 days in total). SFTSV RT-PCR and biochemistry tests were performed at designated time points. Outcomes were 28-day mortality, clinical improvement, viral load evolution, and adverse events (AEs). Twenty-six patients were enrolled, of whom 23 were analyzed. Four of these 23 patients died of multi-organ failure within one week (28-day mortality rate: 17.3%). Oral favipiravir was well tolerated in the surviving patients. AEs (abnormal hepatic function and insomnia) occurred in about 20% of the patients. Clinical symptoms improved in all patients who survived from a median of day 2 to day10. SFTSV RNA levels in the patients who died were significantly higher than those in the survivors (p = 0.0029). No viral genomes were detectable in the surviving patients a median of 8 days after favipiravir administration. The 28-day mortality rate in this study was lower than those of the previous studies in Japan. The high frequency of hepatic dysfunction as an AE was observed. However, it was unclear whether this was merely a side effect of favipiravir, because liver disorders are commonly seen in SFTS patients. The results of this trial support the effectiveness of favipiravir for patients with SFTS., Author summary Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne virus infection caused by Dabie bandavirus (formerly SFTS virus, SFTSV), which belongs to the Bandavirus genus of the Phenuiviridae family. The case fatality rate of patients with SFTS is high ranging from 16.2% to 47%. SFTS is endemic to East and Southeast Asia. Favipiravir, an antiviral agent with an inhibitory activity on the RNA-dependent RNA polymerase, inhibited replication of SFTSV in vitro and in vivo. It was suggested that favipiravir treatment lowered the case fatality rate of patients with SFTS by approximately 10% in comparison with those reported so far through epidemiological survey in Japan. People living in the SFTS-endemic regions can not escape from the risk of being infected with SFTSV. Favipiravir might be an effective drug for treatment of patients with SFTS and reduces the mortality and morbidity of patients with SFTS.

Background Severe fever with thrombocytopenia syndrome (SFTS) is an acute, febrile, and potentially fatal tick-borne disease caused by the SFTS Phlebovirus. Here, we evaluated the effects of steroid therapy in Korean patients with SFTS. Methods A retrospective study was performed in a multicenter SFTS clinical cohort from 13 Korean university hospitals between 2013 and 2017. We performed survival analysis using propensity score matching of 142 patients with SFTS diagnosed by genetic or antibody tests. Results Overall fatality rate was 23.2%, with 39.7% among 58 patients who underwent steroid therapy. Complications were observed in 37/58 (63.8%) and 25/83 (30.1%) patients in the steroid and non-steroid groups, respectively (P < .001). Survival analysis after propensity score matching showed a significant difference in mean 30-day survival time between the non-steroid and steroid groups in patients with a mild condition [Acute Physiology and Chronic Health Evaluation II (APACHE II) score 5 days), and non-steroid groups, were 18.4, 22.4, and 27.3 days, respectively (P = .005). Conclusions After steroid therapy, an increase in complications was observed among patients with SFTS. Steroid therapy should be used with caution, considering the possible negative effects of steroid therapy within 5 days of symptom onset or in patients with mild disease (APACHE II score, Author summary Severe fever with thrombocytopenia syndrome (SFTS) is an acute, febrile, and potentially fatal tick-borne disease caused by the SFTS Phlebovirus. Here, we evaluated the effects of steroid therapy in Korean patients with SFTS. We performed survival analysis using propensity score matching of 142 patients with SFTS diagnosed by genetic or antibody tests. In patients with SFTS, steroid therapy should be used with caution, considering the possible negative effects of steroid therapy within 5 days of symptom onset or in patients with mild disease (APACHE II score

Background Zhejiang Province has the fifth-highest incidence of severe fever with thrombocytopenia syndrome (SFTS) in China. While the top four provinces are all located in northern and central China, only Zhejiang Province is located in the Yangtze River Delta region of southeast China. This study was undertaken to identify the epidemiological characteristics of SFTS in Zhejiang from 2011 to 2018. Methods The epidemic data from SFTS cases in Zhejiang Province from January 2011 to December 2018 were obtained from the China Information Network System of Disease Prevention and Control. Meteorological data were collected from the China Meteorological Data Sharing Service System. A multivariate time series model was used to analyze the heterogeneity of spatial-temporal transmission of the disease. Random forest analysis was performed to detect the importance of meteorological factors and the dose-response association of the incidence of SFTS with these factors. Results In total, 412 SFTS cases (49 fatal) were reported from January 2011 to December 2018 in Zhejiang Province, China. The number of SFTS cases and the number of affected counties increased year by year. The case fatality rate in Zhejiang Province was 11.89%, which was the highest in China. Elderly patients and farmers were the most affected. The total effect values of the autoregressive component, spatiotemporal component and endemic component of the model in all ranges were 0.4580, 0.0377 and 0.0137, respectively. There was obvious heterogeneity across counties for the mean values of the spatiotemporal component and the autoregressive component. The autoregressive component was obviously the main factor driving the occurrence of SFTS, followed by the spatiotemporal component. The importance scores of the monthly mean pressure, mean temperature, mean relative humidity, mean two-minute wind speed, duration of sunshine and precipitation were 10.64, 8.34, 8.16, 6.37, 5.35 and 2.81, respectively. The relationship between these factors and the incidence of SFTS is complicated and nonlinear. A suitable range of meteorological factors for this disease was also detected. Conclusions The autoregressive and spatiotemporal components played an important role in driving the transmission of SFTS. Targeted preventive efforts should be made in different areas based on the main component contributing to the epidemic. For most areas, early measures several months ahead of the suitable season for the occurrence of SFTS should be implemented. The level of reporting and diagnosis of this disease should be further improved., Author summary SFTS is listed as one of the nine most infectious diseases on the WHO priority list. The transmission route and the factors driving the epidemic were complex. Ninety percent of worldwide cases have been reported from China, and Zhejiang Province in China has a high case fatality rate and a high incidence of SFTS. In our study, we found that the numbers of affected counties increased year by year, and the interval from illness onset to confirmation in SFTS was still too long. Furthermore, spatial heterogeneity in the risk factors driving the transmission of SFTS was detected. In addition, the range of suitable weather values for the transmission of SFTS was identified. This suggests that targeted preventive efforts should be made in different areas based on the main factor contributing to the epidemic. In particular, early measures several months ahead of the suitable season for the occurrence of SFTS should be implemented. Enhancement of the level of reporting and diagnosis of this disease should strengthen ongoing research with the incorporation of more risk factors.

Background Severe fever with thrombocytopenia syndrome (SFTS) caused by the SFTS virus is an emerging infectious disease that was first identified in the rural areas of China in 2011. Severe cases often result in death due to multiple organ failure. To date, there are still numerous problems remain unresolved in SFTS, including unclear pathogenesis, lack of specific treatment, and no effective vaccines available. Aim To analyze the clinical information of patients with early-stage SFTS and to establish a nomogram for the mortality risk. Methods Between April 2011 and December 2018, data on consecutive patients who were diagnosed with SFTS were prospectively collected from five medical centers distributed in central and northeastern China. Multivariable Cox analyses were used to identify the factors independently associated with mortality. A nomogram for mortality was established using those factors. Results During the study period, 429 consecutive patients were diagnosed with SFTS at the early stage of the disease (within 7 days of fever), among whom 69 (16.1%) died within 28 days. The multivariable Cox proportional hazard regression analysis showed that low lymphocyte percentage, early-stage encephalopathy, and elevated concentration of serum LDH and BUN were independent risk factors for fatal outcomes. Received-operating characteristic curves for 7-, 14-, and 28-days survival had AUCs of 0.944 (95% CI: 0.920–0.968), 0.924 (95% CI: 0.896–0.953), and 0.924 (95% CI: 0.895–0.952), respectively. Among low-risk patients, 6 patients died (2.2%). Among moderate-risk patients, 25 patients died (24.0%, hazard ratio (HR) = 11.957). Among high-risk patients, the mortality rate was 69.1% (HR = 57.768). Conclusion We established a simple and practical clinical scoring system, through which we can identify critically ill patients and provide intensive medical intervention for patients as soon as possible to reduce mortality., Author summary We established a SFTS nomogram scoring system, which is the first nomogram for this disease. According to this nomogram, patients were divided into three levels of mortality risk: low, moderate, and high. This scoring system is helpful to identify critically ill patients, allowing for early intervention and intensive care, which may contribute to reducing the mortality of SFTS.

Background Severe fever with thrombocytopenia syndrome (SFTS) is a severe emerging disease caused by SFTS virus (SFTSV), and the geographical distribution of SFTS has been increasing throughout China in recent years. To assess SFTSV-specific antibody seroprevalence, a cross-sectional study was conducted for healthy people in high SFTS endemic areas of Henan province in 2016. Methods This study used a stratified random sampling method to select 14 natural villages as the investigation sites. From April to May 2016, participants completed a questionnaire survey and serum samples were collected. All serum samples were subjected to ELISA to detect SFTSV-specific IgM and IgG. All IgM-positive samples were further tested by real-time RT-PCR, and isolation of virus from serum was attempted. Any participant who was IgM-positive was followed up with a month later to confirm health status. Results In total, 1463 healthy people participated in this study. The average seropositive rates for SFTSV-specific IgG and IgM were 10.46% (153/1463) and 0.82% (12/1463), respectively. IgM was detected in 12 individuals, and SFTSV RNA was detected in six of them. Virus was isolated from five of the six SFTSV RNA-positive individuals, and phylogenetic analyses revealed that all five isolates belonged to SFTSV group A. No IgM-positive participants exhibited any symptoms or other signs of illness at the one-month follow up. Conclusions This study identified a relatively high incidence of SFTSV-specific antibody seropositivity in healthy people in Xinyang city. Moreover, our data provide the first evidence for asymptomatic SFTSV infections, which may have significant implications for SFTS outbreak control., Author summary Severe fever with thrombocytopenia syndrome (SFTS) is a severe emerging infectious disease caused by SFTS virus (SFTSV) that was first discovered in rural areas of China. Henan province has had the largest number of SFTS cases in China every year since the disease was discovered, however, seropositivity for SFTSV-specific antibodies in healthy people in this region is still not clear. To address this issue, a cross-sectional survey was performed in high endemic areas from April to May 2016. The results showed that SFTSV seroprevalence was relatively high and possibly increasing. Notably, SFTSV RNA, as well as virus itself, was isolated from specimens obtained from healthy people. This study confirmed there are asymptomatic SFTSV infections in humans, and it is the first to report SFTSV isolation from healthy people.

Background Severe fever with thrombocytopenia syndrome (SFTS) was listed as one of the most severe infectious disease by world health organization in 2017. It can mostly be transmitted by tick bite, while human-to-human transmission has occurred on multiple occasions. This study aimed to explore the epidemiological and clinical characteristics and make risk analysis of SFTS human-to-human transmission. Methods Descriptive and spatial methods were employed to illustrate the epidemiological and clinical characteristics of SFTS human-to-human transmission. The risk of SFTS human-to-human transmission was accessed through secondary attack rate (SAR) and basic reproductive number (R0). Logistic regression analysis was used to identify the associated risk factors. Results A total of 27 clusters of SFTS human-to-human transmission were reported in China and South Korea during 1996–2019. It mainly occurred among elder people in May, June and October in central and eastern China. The secondary cases developed milder clinical manifestation and better outcome than the index cases. The incubation period was 10.0 days (IQR:8.0–12.0), SAR was 1.72%-55.00%, and the average R0 to be 0.13 (95%CI:0.11–0.16). Being blood relatives of the index case, direct blood/bloody secretion contact and bloody droplet contact had more risk of infection (OR = 6.35(95%CI:3.26–12.37), 38.01 (95%CI,19.73–73.23), 2.27 (95%CI,1.01–5.19)). Conclusions SFTS human-to-human transmission in China and South Korea during 1996–2019 had obvious spatio-temporal distinction. Ongoing assessment of this transmission risk is crucial for public health authorities though it continues to be low now., Author summary This study is first to explore the epidemiological and clinical characteristics of SFTS human-to-human transmission. We found SFTS human-to-human transmission had obvious characteristic temporal and spatial distinction, which mainly occurred among elder people in May, June and October in the central and eastern China. The secondary cases developed milder clinical manifestation and better outcome than the index cases. The incubation period was 10.0 days (IQR:8.0–12.0). The risk of SFTS human-to-human transmission continues to be low, with the secondary attack rate (SAR) among humans was 1.72%-55.00% and basic reproductive number (R0) to be 0.13 (95%CI:0.11–0.16). Being blood relatives of the index case, direct blood/bloody secretion contact and bloody droplet contact had more risk of acquiring infection.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that is caused by a novel bunyavirus SFTSV. Currently our knowledge of the host-related factors that influence the pathogenesis of disease is inadequate to allow prediction of fatal outcome. Here we conducted a prospective study of the largest database on the SFTS patients, to identify the presence of comorbidities in SFTS, and estimate their effect on the fatal outcome. Among 2096 patients eligible for inclusion, we identified nine kinds of comorbidities, from which hyperlipidemia (12.2%; 95% CI: 10.8%–13.6%), hypertension (11.0%; 95% CI: 9.6%–12.3%), chronic viral hepatitis (CVH) (9.3%; 95% CI: 8.1%–10.5%), and diabetes mellitus (DM) (6.8%; 95% CI: 5.7%–7.9%) were prevalent. Higher risk of death was found in patients with DM (adjusted OR = 2.304; 95% CI: 1.520–3.492; P, Author summary SFTS now brings about a substantial global public health concern. Preexisting chronic conditions were thought to increase risk of severe SFTSV infections, however with sparse data mining efforts. In this study, we quantified the frequency of chronic comorbidities in SFTS, estimated their contribution to disease severity, and separately evaluated the effect from diabetes mellitus and chronic viral hepatitis on resulting in fatal outcome.

Background Severe fever with thrombocytopenia syndrome (SFTS) is an emerging viral hemorrhagic fever with a high fatality rate and high frequency of person-to-person transmission and is caused by SFTSV, a tick-borne Phlebovirus. Because SFTS has similar clinical manifestations and epidemic characters (such as spatial and temporal distributions) with hemorrhagic fever with renal syndrome (HFRS) in China, we reason that SFTS patients might be misdiagnosed as HFRS. Methodology/principal findings Acute-phase sera of 128 clinically diagnosed HFRS patients were retrospectively analyzed for Hantavirus IgM antibodies with ELISA. Hantavirus-negative patients’ sera were further analyzed for SFTSV IgM antibodies with ELISA. ELISA showed that 73 of 128 (57.0%) of clinically diagnosed HFRS patients were IgM antibody positive to Hantaviruses. Among the 55 Hantavirus-IgM negative patients, four (7.3%) were IgM antibody positive to SFTSV. The results indicated that the four SFTS patients were misdiagnosed as HFRS. The misdiagnosed SFTS patients had clinical manifestations common to HFRS and were unable to be differentiated from HFRS clinically. Conclusions Our study showed that SFTS patients could be clinically misdiagnosed as HFRS. The misdiagnosis of SFTS as HFRS causes particular concern because it may increase the risk of death of SFTS patients and person-to-person transmission of SFTSV without proper care for and isolation of SFTS patients.

Background Severe fever with thrombocytopenia syndrome virus (SFTSV), an emerging human pathogen naturally transmitted by ticks, has spread widely since it was first detected in 2010. Although SFTSV-specific antibodies have been detected in wild birds, these natural reservoir and amplifying hosts for the virus have not been well studied. Methodology/Principle findings Here we report an experimental infection of spotted doves (Streptopelia chinensis) with two strains of SFTSV, JS2010-14, a Chinese lineage strain, and JS2014-16, a Japanese lineage strain, which represent the main viral genotypes currently circulating in East Asia. In these studies, we have determined that spotted doves are susceptible to SFTSV and the severity of the viremia is dose-dependent. When challenged with 107 and 105 PFU, all doves developed viremia which peaked 3–5 days post infection (dpi). Only a subset (25–62.5%) of the birds developed viremia when challenged at 103 PFU. Virulence of SFTSV in spotted doves was strain dependent. Infection with 107 PFU of strain JS2014-16 resulted in 12.5% mortality over 6.8 days and mean peak viremia titers of 106.9 PFU/mL in experimentally inoculated birds. All doves inoculated with 107 PFU of the JS2010-14 strain survived infection with relatively lower mean viremia titers (105.6 PFU/mL at peak) over 6.1 days. Conclusions/Significance Our results suggest that spotted doves, one of the most abundant bird species in China, could be a competent amplifying host for SFTSV and play an important role in its ecology. Between the two SFTSV strains, the strain of the Japanese lineage caused mortality, higher viremia titers in infected birds over a longer time period than did the Chinese strain. Our observations shed light on the ecology of SFTSV, which could benefit the implementation of surveillance and control programs., Author summary Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging human pathogen naturally transmitted by ticks. Our recent study has showed that some species of migratory birds, such as swan geese and spotted doves, can be parasitized by Haemaphysalis longicornis, an SFTSV vector, and antibodies against the SFTSV detected in these species. These data demonstrate that migratory birds are infected with SFTSV and may also play a role in the infection of ticks with SFTSV. Other studies have reported that migratory bird routes and the distribution of H. longicornis in East Asia overlap with the geographic distribution of SFTSV. Migratory birds are known to be carriers and transmitters of infectious agents, like the causative agents of influenza, West Nile encephalitis, and Lyme disease. Wild birds often travel long distances carrying various parasites, including ticks, which may be infected with viruses and bacteria. It is therefore reasonable to hypothesize that migratory birds may have played an important role in spreading SFTSV in two potential transmission scenarios: 1) birds are infected with the virus and transmit it back to ticks endemically or in a distal region, or 2) they are carriers of parasitic ticks that are infected with the virus. Here we report an experimental infection of spotted doves (Streptopelia chinensis) with two strains of SFTSV, JS2010-14 from a Chinese lineage and JS2014-16 from a Japanese lineage, which represent the main viral genotypes currently circulating in East Asia. We determined that spotted doves are susceptible to SFTSV and that the severity of the viremia was dose and strain dependent. Infection with the strain of JS2014-16 led to a death rate of 12.5% and higher viremia titers in experimentally inoculated birds while doves inoculated with the JS2010-14 strain survived infection with relatively lower virus titers in the blood. These findings provide novel insights for understanding the rapid spread of the virus in a short time span, in particular the SFTSV strains from the Japanese lineage (genotype E).

Severe Fever with Thrombocytopenia Syndrome (SFTS) is an emerging infectious disease caused by a novel bunyavirus, SFTS virus (SFTSV), with fatal outcome developed in approximately 17% of the cases. Thrombocytopenia is a hallmark feature of SFTS, and associated with a higher risk of fatal outcome, however, the pathophysiological involvement of platelet in the clinical outcome of SFTS remained under-investigated. In the current study, by retrospectively analyzing 1538 confirmed SFTS patients, we observed that thrombocytopenia was associated with enhanced activation of the cytokine network and the vascular endothelium, also with a disturbed coagulation response. The platelet phenotypes were also extensively altered in the process of thrombocytopenia development of SFTS patients. More importantly, all these disturbed host responses were related to the severity of thrombocytopenia, thus were considered to play in a synergistic way to influence the disease outcome. Moreover, the clinical effect of platelet transfusion was assessed by comparing two groups of patients with or without receiving this therapy. As a result, we observed no therapy effect in altering frequencies of fatal outcome, clinical bleeding development, or dynamic change of platelet count during the hospitalization. It’s suggested that platelet supplementation alone acted a minor role in improving disease outcome, therefore new therapeutic intervention to regulate host response should be proposed. The current results revealed some evidence of interrelationship between platelet count and clinical outcome of SFTS disease from the perspective of activation of the cytokine network, the vascular endothelium, and the coagulation/fibrinolysis system. These evaluations might help to attain a better understanding of the pathogenesis and therapy choice in SFTS., Author summary Thrombocytopenia in SFTSV is a multifactor-process involving a combination of platelet size or morphology alterations, fibrinolysis activation and coagulation abnormalities, increased inflammatory response and endothelial injury. Platelet supplementation alone shows minor role in improving disease, therefore new therapeutic intervention to regulate host response should be proposed.

Background A cluster of eleven patients, including eight family members and three healthcare workers with fever and thrombocytopenia occurred in Yixing County, Jiangsu Province, China, from October to November 1996. However, the initial investigation failed to identify its etiology. Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by SFTS bunyavirus (SFTSV), which was first discovered in 2009. The discovery of novel SFTSV resulted in our consideration to test SFTSV on the remaining samples of this cluster in September 2010. Methodology/Principal findings We retrospectively analyzed the epidemiological and clinical data of this cluster. The first case, one 55-year-old man with fulminant hemorrhagic diseases, died on October 14, 1996. His younger brother (the second case) developed similar hemorrhagic diseases after nursing him and then died on November 3. From November 4 to November 15, nine other patients, including six family members and three medical staffs, developed fever and thrombocytopenia after exposure to the second case. The sera of six patients were collected on November 24, 1996. IgM antibodies against SFTSV were detected in all of the six patients’ sera using enzyme-linked immunosorbent assay (ELISA), while IgG antibodies were detected in one patient’s serum using an indirect immunofluorescence assay (IFA). We also found that IgG antibodies against SFTSV were still detected in four surviving patients’ sera 14 years after illness onset. Conclusions and significance The mysterious pathogen of the cluster in 1996 was proved to be SFTSV on the basis of its epidemiological data, clinical data and serological results. It suggests that SFTSV has been circulating in China for more than 10 years before being identified in 2009, and SFTSV IgG antibodies can persist for up to 14 years., Author summary SFTSV was first discovered in 2009. It can be transmitted through tick bites, direct contact with SFTS patients’ blood or bloody secretion, and probable aerosol transmission. SFTS was listed as one of the nine infectious diseases on the WHO priority list in 2017 because of its trend of wider distribution and rising threat imposed on global health. It is worth mentioning that a cluster of eleven patients including eight family members and three healthcare workers developed fever and thrombocytopenia in China, from October to November 1996, but the initial investigation failed to identify its etiology. A retrospective analysis was conducted in September 2010. Based on the epidemiological, clinical, and serological findings, we speculated that SFTSV was the mysterious pathogen of the cluster. Meanwhile, high-titer SFTSV IgG antibodies were detected in four surviving patients’ sera. These SFTS patients preceded two cases in Japan in 2005 reported by Kurihara et al., which were once regarded as “the earliest SFTS cases worldwide”. These results suggest that SFTS should have existed without being diagnosed for a long time, and SFTSV IgG antibodies can persist long for 14 years, and perhaps even a lifetime after infection.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that is caused by a novel bunyavirus, SFTSV. We assessed whether the single nucleotide polymorphisms (SNPs) in the tumor necrosis factor-alpha (TNF-α) were associated with risk to severity of SFTS. Five TNF-α SNPs (SNP1: T-1031C; SNP2: C-863A; SNP3: C-857T; SNP4: G-308A; SNP5: G-238A) were genotyped in 987 hospitalized SFTS patients and 633 asymptomatic/mild SFTSV-infected subjects of Chinese Han origin. Multivariate logistic regression analysis was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs). The hospitalized SFTS patients had significantly lower frequency of G-238A A allele than those with mild/asymptomatic infection (P = 0.006). Furthermore, T-1031C C allele (P < 0.001) and G-238A A allele (P < 0.001) were significantly associated with decreased risk of death. Multiple haplotypes were significantly associated with decreased risk of SFTS hospital admission (SNP1-2, CC; SNP1-3, CCC; SNP1-4, CCCG; SNP1-5, CCCGA; SNP2-4, CCGA; SNP3-5, CGA; SNP4-5, GA) and death (SNP1-2, CA; SNP1-3, CAG; SNP1-4, CACG; SNP1-5, CACGG; SNP2-3, AC; SNP2-4, ACG; SNP2-5, ACGG) after correction for multiple comparisons. By using the ELISA assay, we observed that TNF-α concentration of hospitalized patients was significantly increased in acute phase than in convalescent phase (P < 0.001). Elevated TNF-α concentration was also revealed from fatal patients (P < 0.001). The -238A allele was associated with decreased serum TNF-α levels in SFTS patients in acute phase (P = 0.01). Our findings suggest that polymorphisms in TNF-α gene may play a role in mediating the risk to disease severity of SFTS in Chinese Han population., Author summary Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that is caused by a novel bunyavirus. The current study disclosed the single nucleotide polymorphisms (SNPs) in the tumor necrosis factor-alpha (TNF-α) were associated with risk to disease severity of SFTS. These findings suggest that polymorphisms in TNF-α gene may play a role in mediating the risk to disease severity of SFTS in Chinese Han population. The study will be of interest to either the clinicians devoted to the prevention and therapy of SFTS or the geneticists devoted to studying the genetic susceptibility mechanisms of common diseases.

Background Severe 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 findings In 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/Significance Full-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., Author summary Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne viral disease caused by the SFTS virus (SFTSV). During entomological surveillance of SFTSV infection in Korean ticks collected from SFTS outbreak areas, we isolated a single SFTSV strain which we designated KAGWT. In addition, we isolated three SFTSVs from human patients with typical SFTS symptoms. In this study, we report the genomic sequences of each of these isolates and compare the genetic and evolutionary characteristics between tick- and human-derived Korean SFTSV isolates. Genetic and phylogenetic analyses of these sequences revealed that the tick-derived Korean SFTSV strain is clustered into genotype B, the most prevalent genotype in South Korea, and was closely related to other SFTSV in the same group. Furthermore, our results show that at least four different genotypes of SFTSV strains are co-circulating in South Korea.

Background Pathogenesis of severe fever with thrombocytopenia syndrome (SFTS) has not been well described yet. Recent studies indicate that SFTSV could replicate in endothelial cells. Here we performed a case-control study to determine whether endothelial activation/dysfunction occurred in SFTSV infection and to identify the biomarkers reflecting endothelial dysfunction. Methodology/Principal findings In a case-control study of 134 SFTS patients and 68 healthy controls, serum levels of plasminogen activator inhibitor 1, tissue plasminogen activator, P-selectin, platelet endothelial cell adhesion molecular, CD40 ligand, E-selectin, vascular endothelial growth factor A, serum amyloid antigen 1 (SAA-1) and vascular cell adhesion molecular 1 were significantly enhanced in the patients than the controls (all P, Author summary Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne viral disease and first reported in the rural areas of China. Pathogenesis of the disease has not been well described yet. Recent studies indicated that SFTSV replicated in endothelial cells. So, we performed a case-control study to explore whether endothelial activation/dysfunction occurred in SFTSV infection and to identify biomarkers reflecting endothelial dysfunction. We found that the occurrence of endothelial activation/dysfunction in severe fever with thrombocytopenia syndrome and the serum levels of ICAM-1 and SAA-1 might be used to predict adverse outcome.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging epidemic infectious disease caused by the SFTS bunyavirus (SFTSV) with an estimated high case-fatality rate of 12.7% to 32.6%. Currently, the disease has been reported in mainland China, Japan, Korea, and the United States. At present, there is no specific antiviral therapy for SFTSV infection. Considering the higher mortality rate and rapid clinical progress of SFTS, supporting the appropriate treatment in time to SFTS patients is critical. Therefore, it is very important for clinicians to predict these SFTS cases who are more likely to have a poor prognosis or even more likely to decease. In the present study, we established a simple and feasible model for assessing the severity and predicting the prognosis of SFTS patients with high sensitivity and specificity. This model may aid the physicians to immediately initiate prompt treatment to block the rapid development of the illness and reduce the fatality of SFTS patients., Author summary Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by a novel SFTS bunyavirus (SFTSV) with an estimated high case-fatality rate. However, there is no specific antiviral therapy for SFTSV infection. Symptomatic treatment and supportive therapy are the most essential part of case management. It is very important for clinicians to identify critical patients at admission. In this study, we established a simple and feasible scoring system for assessing the severity and predicting the prognosis of SFTS patients with objective parameters. This model may help the physicians to perform intervention measures in advance, control the disease progression and improve the prognosis.

Background Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that was recently identified in China, South Korea and Japan. The objective of the study was to evaluate the epidemiologic and clinical characteristics of SFTS in South Korea. Methods/Principal Findings SFTS is a reportable disease in South Korea. We included all SFTS cases reported to the Korea Centers for Disease Control and Prevention (KCDC) from January 2013 to December 2015. Clinical information was gathered by reviewing medical records, and epidemiologic characteristics were analyzed using both KCDC surveillance data and patient medical records. Risk factors for mortality in patients with SFTS were assessed. A total of 172 SFTS cases were reported during the study period. SFTS occurred throughout the country, except in urban areas. Hilly areas in the eastern and southeastern regions and Jeju island (incidence, 1.26 cases /105 person-years) were the main endemic areas. The yearly incidence increased from 36 cases in 2013 to 81 cases in 2015. Most cases occurred from May to October. The overall case fatality ratio was 32.6%. The clinical progression was similar to the 3 phases reported in China: fever, multi-organ dysfunction, and convalescence. Confusion, elevated C-reactive protein, and prolonged activated partial thromboplastin times were associated with mortality in patients with SFTS. Two outbreaks of nosocomial SFTS transmission were observed. Conclusions SFTS is an endemic disease in South Korea, with a nationwide distribution and a high case-fatality ratio. Confusion, elevated levels of C-reactive protein, and prolonged activated partial thromboplastin times were associated with mortality in patients with SFTS., Author Summary Severe fever with thrombocytopenia (SFTS) is an emerging infectious disease that was first discovered in China in 2009. Subsequently, SFTS has also been found in South Korea and Japan. Here, we report the epidemiologic and clinical characteristics of 172 confirmed SFTS cases in South Korea that occurred since the first case was reported in 2013. SFTS was prevalent throughout South Korea, except for in urban areas. The incidence was relatively low in the western and southwestern rice field areas and the scarcely populated eastern mountainous area. Hilly areas were the major endemic regions. The incidence was increasing annually, and the case fatality ratio was 32.6%. A mental status of confusion, elevated levels of C-reactive protein, and prolongation of activated partial thromboplastin time were associated with mortality in patients with SFTS. Two outbreaks of nosocomial SFTS transmission were noted.

Background Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne infectious disease with a high case fatality rate, and is caused by the SFTS virus (SFTSV). SFTS is endemic to China, South Korea, and Japan. The viral RNA level in sera of patients with SFTS is known to be strongly associated with outcomes. Virological SFTS diagnosis with high sensitivity and specificity are required in disease endemic areas. Methodology/Principal Findings We generated novel monoclonal antibodies (MAbs) against the SFTSV nucleocapsid (N) protein and developed a sandwich antigen (Ag)-capture enzyme-linked immunosorbent assay (ELISA) for the detection of N protein of SFTSV using MAb and polyclonal antibody as capture and detection antibodies, respectively. The Ag-capture system was capable of detecting at least 350–1220 TCID50/100 μl/well from the culture supernatants of various SFTSV strains. The efficacy of the Ag-capture ELISA in SFTS diagnosis was evaluated using serum samples collected from patients suspected of having SFTS in Japan. All 24 serum samples (100%) containing high copy numbers of viral RNA (>105 copies/ml) showed a positive reaction in the Ag-capture ELISA, whereas 12 out of 15 serum samples (80%) containing low copy numbers of viral RNA (, Author Summary Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne emerging infectious disease caused by a novel bunyavirus, SFTS virus (SFTSV). Since first discovered in China in 2011, SFTSV has been detected from SFTS patients and ticks with expanding geographic ranges from China to Japan and South Korea. The potential for SFTS spread to other warm or sub-tropical regions makes it a serious concern to the public health. It is of great importance to detect SFTSV rapidly and specifically for the effective control of the disease. For the diagnosis of viral infections, a sandwich antigen (Ag)-capture ELISA detecting viral nucleoprotein (N) in viremic serum samples has been widely applied to detect the agents, since it is the most abundant viral antigen and has highly conserved amino acid sequence. In this study, using the novel monoclonal antibodies raised against SFSTV-N, an Ag-capture ELISA system was developed, and the validation of this system was performed using sera collected from SFTS-suspected patients. Our data show that the Ag-capture ELISA was useful for the diagnosis of SFTS patients in the acute phase of the disease. This study shows a novel methodology for the diagnosis of SFTS, which may provide helpful information for the effective control of the disease.

Background Severe fever with thrombocytopenia syndrome (SFTS) is an emerging disease that is caused by a novel bunyavirus, referred to as SFTS virus. During January 2011 to December 2011 we conducted a case-control study in Henan, Hubei and Shandong Provinces of China to determine the risk factors for SFTS. Methods Case-patients were identified in hospitals and reported to provincial Centers for Disease Control and Prevention while being notified electronically to the National Surveillance System. Controls were randomly selected from a pool of patients admitted to the same hospital ward within one week of the inclusion of the cases. They were matched by age (+/−5 years) and gender. Results A total of 422 patients participated in the study including 134 cases and 288 matched controls. The median age of the cases was 58.8 years, ranging from 47.6 to 70.1 years; 54.5% were male. No differences in demographics were observed between cases and controls; however, farmers were frequent and more common among cases (88.8%) than controls (58.7%). In multivariate analysis, the odds for SFTS was 2.4∼4.5 fold higher with patients who reported tick bites or presence of tick in the living area. Other independent risk factors included cat or cattle ownership and reported presence of weeds and shrubs in the working environment. Conclusions Our findings support the hypothesis that ticks are important vectors of SFTS virus. Further investigations are warranted to understand the detailed modes of transmission of SFTS virus while vector management, education on tick bites prevention and personal hygiene management should be implemented for high-risk groups in high incidence areas., Author Summary Since 2009, an emerging infectious disease which was identified as the severe fever with thrombocytopenia syndrome (SFTS) was reported in rural areas of Hubei, Shandong and Henan provinces in China. A novel bunyavirus designated severe fever with thrombocytopenia syndrome bunyavirus (SFTSV) had been identified to be the etiological cause of SFTS. But what risk factors lead to the disease is still not clear. Further investigations for risk factors are needed to effectively prevent and control the disease. Here we have designed case-control study to try to develop the risk factors of the spread of SFTSV. It is hoped that our research could provide epidemiological evidence for further study. Also help to determine the spread of the virus in the environment.

Objective Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever caused by a tick-borne bunyavirus (SFTSV) in East Asian countries. The role of human leukocyte antigen (HLA) in resistance and susceptibility to SFTSV is not known. We investigated the correlation of HLA locus A, B and DRB1 alleles with the occurrence of SFTS. Methods A total of 84 confirmed SFTS patients (patient group) and 501 unrelated non-SFTS patients (healthy individuals as control group) from Shandong Province were genotyped by PCR-sequence specific oligonucleotide probe (PCR-SSOP) for HLA-A, B and DRB1 loci.Allele frequency was calculated and compared using χ2 test or the Fisher's exact test. A corrected P value was calculated with a bonferronis correction. Odds Ratio (OR) and 95% confidence intervals (CI) were calculated by Woolf’s method. Results A total of 11 HLA-A, 23 HLA-B and 12 HLA-DRB1 alleles were identified in the patient group, whereas 15 HLA-A, 30 HLA-B and 13 HLA-DRB1 alleles were detected in the control group. The frequencies of A*30 and B*13 in the SFTS patient group were lower than that in the control group (P = 0.0341 and 0.0085, Pc = 0.5115 and 0.252). The ORs of A*30 and B*13 in the SFTS patient group were 0.54 and 0.49, respectively. The frequency of two-locus haplotype A*30-B*13 was lower in the patient group than in the control group(5.59% versus 12.27%, P = 0.037,OR = 0.41, 95%CI = 0.18–0.96) without significance(Pc>0.05). A*30-B*13-DRB1*07 and A*02-B*15-DRB1*04 had strong associations with SFTS resistance and susceptibility respectively (Pc = 0.0412 and 0.0001,OR = 0.43 and 5.07). Conclusion The host HLA class I polymorphism might play an important role with the occurrence of SFTS. Negative associations were observed with HLA-A*30, HLA-B*13 and Haplotype A*30-B*13, although the associations were not statistically significant. A*30-B*13-DRB1*07 had negative correlation with the occurrence of SFTS; in contrast, haplotype A*02-B*15-DRB1*04 was positively correlated with SFTS., Author Summary Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever caused by a tick-borne bunyavirus (SFTSV) in East Asian countries. The role of human leukocyte antigen (HLA) in resistance and susceptibility to SFTSV is not known. In this study, we investigated the correlation of HLA locus A, B and DRB1 alleles with the occurrence of SFTS. Our results have expanded the knowledge of the association of HLA genes with SFTS. Our study may be helpful to state the relationship between the occurrence of SFTS with HLA alleles or haplotypes and provide scientific basis for study on pathogenesis and vaccine development.

Background Severe fever with thrombocytopenia syndrome virus (SFTSV), the causative agent for the fatal life-threatening infectious disease, severe fever with thrombocytopenia syndrome (SFTS), was first identified in the central and eastern regions of China. Although the viral RNA was detected in free-living and parasitic ticks, the vector for SFTSV remains unsettled. Methodology/Principal Findings Firstly, an experimental infection study in goats was conducted in a bio-safety level-2 (BSL-2) facility to investigate virus transmission between animals. The results showed that infected animals did not shed virus to the outside through respiratory or digestive tract route, and the control animals did not get infected. Then, a natural infection study was carried out in the SFTSV endemic region. A cohort of naïve goats was used as sentinel animals in the study site. A variety of daily samples including goat sera, ticks and mosquitoes were collected for viral RNA and antibody (from serum only) detection, and virus isolation. We detected viral RNA from free-living and parasitic ticks rather than mosquitoes, and from goats after ticks’ infestation. We also observed sero-conversion in all members of the animal cohort subsequently. The S segment sequences of the two recovered viral isolates from one infected goat and its parasitic ticks showed a 100% homology at the nucleic acid level. Conclusions/Significance In our natural infection study, close contact between goats does not appear to transmit SFTSV, however, the naïve animals were infected after ticks’ infestation and two viral isolates derived from an infected goat and its parasitic ticks shared 100% of sequence identity. These data demonstrate that the etiologic agent for goat cohort’s natural infection comes from environmental factors. Of these, ticks, especially the predominant species Haemaphysalis longicornis, probably act as vector for this pathogen. The findings in this study may help local health authorities formulate and focus preventive measures to contain this infection., Author Summary Severe fever with thrombocytopenia syndrome virus (SFTSV), a newly identified bunyavirus, has been found to circulate in mainland China, South Korea, and Japan since 2009. This virus is the etiologic agent for an emerging fatal hemorrhagic fever, severe fever with thrombocytopenia syndrome (SFTS) with high fatality. Although ticks have been implicated as the primary host vector indicated by epidemiological surveys, their role in transmitting this virus to the susceptible hosts, including humans, has not been validated. In this study, we conducted experimental and natural infections of goats with SFTSV to explore the role of ticks for this pathogen’s transmission. In the experimental infection study, we have not found any viral transmission within the cohort by close contact between animals. However, in the natural infection study, every member of a naïve goat cohort was observed to get infected sequentially when they were farmed in a SFTSV-endemic site. We detected viral RNA from free-living and parasitic ticks rather than mosquitoes, and from goats after ticks’ infestation. We also observed sero-conversion in all members of the animal cohort subsequently. More importantly, in the natural infection study, two virus strains isolated from one infected goat and its parasitic ticks showed identical S segment sequences of the viral genome. All these findings indicate that ticks, especially the dominant species Haemaphysalis longicornis, probably act as viral vector for this emerging pathogen, SFTSV.