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Autophagy is emerging as a critical player in host defense against diverse infections, in addition to its conserved function to maintain cellular homeostasis. Strikingly, some pathogens have evolved strategies to evade, subvert or exploit different steps of the autophagy pathway for their lifecycles. Here, we present a new viral mechanism of manipulating autophagy for its own benefit with severe fever with thrombocytopenia syndrome bunyavirus (SFTSV, an emerging high-pathogenic virus) as a model. SFTSV infection triggers autophagy, leading to complete autophagic flux. Mechanistically, we show that the nonstructural protein of SFTSV (NSs) interacts with mTOR, the pivotal regulator of autophagy, by targeting its kinase domain and captures mTOR into viral inclusion bodies (IBs) induced by NSs itself. Furthermore, NSsimpairs mTOR-mediated phosphorylation of unc-51-like kinase 1 (ULK1) at Ser757, disrupting the inhibitory effect of mTOR on ULK1 activity and thus contributing to autophagy induction. Pharmacologic treatment and Beclin-1 knockout experimental results establish that, in turn, autophagy enhances SFTSV infection and propagation. Moreover, the minigenome reporter system reveals that SFTSV ribonucleoprotein (the transcription and replication machinery) activity can be bolstered by autophagy. Additionally, we found that the NSs proteins of SFTSV-related bunyaviruses have a conserved function of targeting mTOR. Taken together, we unravel a viral strategy of inducing pro-viral autophagy by interacting with mTOR, sequestering mTOR into IBs and hence provoking the downstream ULK1 pathway, which presents a new paradigm for viral manipulation of autophagy and may help inform future development of specific antiviral therapies against SFTSV and related pathogens., (© 2022 Wiley Periodicals LLC.)

We report a 57-year-old man with acute thrombocytopenia, leucopenia, and multiorgan dysfunction. Patient was from North Korea and was temporarily working in Dubai, United Arab Emirates, when he fell ill in March 2009. At the same time and unknown to us, many patients with similar clinical manifestations were admitted to hospitals in China. The Chinese cases—identified between March and July 2009—were recently reported to have been infected with a tick-born strain of bunyavirus, a new disease. The virus infection was documented in patients from central China and the region that shares the border with North Korea. The clinical manifestations, the time of disease onset, and geographical link of the patient with the region in which the disease is endemic suggest that the patient had SFTS bunyavirus infection.

To understand the maintenance and transmission of SFTS virus, the potential vector ticks were collected from sheep, cattle and dogs in the endemic areas of SFTSV in Shandong Province. Among the collected ticks, the dominant species was H. longicornis ticks. Real-time PCR for RNA detection, virus isolation and characterization, genomic sequencing, phylogenetic and antigenic analysis were performed in this investigation. The results showed that the SFTS viral RNA was detected in 2.14% H. longicornis, and a SFTS virus was isolated from one of viral RNA positive ticks collected from sheep. Whole genome analysis of the SFTSV isolates with 11 human-origin SFTS virus revealed a highly pairwise similarity, and the growth curve analysis showed nearly identical in virus yield and the dynamic of virus reproduction compared to human derived viral isolates. Immunofluorescence and neutralization test showed identical serological reaction character of the two different origin viral strains. In this study, the characters of a SFTSV isolate was firstly described, which suggested that the tick species H. longicornis acting important vector role in the transmission of SFTS virus.

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease recently identified to be caused by a novel bunyavirus (SFTSV). The clinical diagnosis is urgently needed to differentiate the disease from other infections., Objective: To develop a sensitive quantitative real-time RT-PCR assay for rapid detection of SFTSV viral RNA and evaluate potential use for clinical diagnosis of SFTS., Study Design: Primers and probes were designed to target the L, M, and S segments of SFTSV, and standard curves were established based on serial dilutions of in vitro transcribed viral RNA or viral RNA extracts. The serum samples collected from 70 laboratory confirmed SFTS patients, 114 non-SFTS patients, and 400 healthy donors were analyzed., Results: Based on three optimized primer-probe sets to detect L, M, S genes of SFTSV, the quantitative real-time RT-PCR assay could discriminate SFTSV infection from other vector-borne viral diseases in human with potential detection limit of 10 viral RNA copies/μl or 10 TCID(50)/ml virus load. Strong linear correlations (r(2)>0.99) between the C(t) values and viral RNA standards over a liner range were obtained. The assay specificity was determined by sequence alignment and experimentally tested on various related viruses. Evaluation of the study method with clinical serum samples showed 98.6% clinical diagnostic sensitivity and over 99% specificity., Conclusion: The quantitative real-time RT-PCR assay established in this study can be used as a reliable method for early diagnosis of SFTSV infection., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Copyright of China Tropical Medicine is the property of China Tropical Medicine Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Severe fever with thrombocytopenia syndrome (SFTS), an emerging life-threatening infectious disease caused by SFTS bunyavirus (SFTSV; genus Bandavirus , family Phenuiviridae , order Bunyavirales), has been a significant medical problem. Currently, there are no licensed vaccines or specific therapeutic agents available and the viral pathogenesis remains largely unclear. Developing appropriate animal models capable of recapitulating SFTSV infection in humans is crucial for both the study of the viral pathogenic processes and the development of treatment and prevention strategies. Here, we review the current progress in animal models for SFTSV infection by summarizing susceptibility of various potential animal models to SFTSV challenge and the clinical manifestations and histopathological changes in these models. Together with exemplification of studies on SFTSV molecular mechanisms, vaccine candidates, and antiviral drugs, in which animal infection models are utilized, the strengths and limitations of the existing SFTSV animal models and some important directions for future research are also discussed. Further exploration and optimization of SFTSV animal models and the corresponding experimental methods will be undoubtedly valuable for elucidating the viral infection and pathogenesis and evaluating vaccines and antiviral therapies. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by the tick-borne SFTS bunyavirus (SFTSV) resulting in a high fatality rate up to 30%. SFTSV is a negative-strand RNA virus containing three single-stranded RNA genome segments designated as L, M, and S, which respectively, encode the RNA-dependent RNA polymerase (RdRp), glycoproteins Gn and Gc, and nucleoprotein (N) and non-structural proteins (NSs). NSs can form inclusion bodies (IBs) in infected and transfected cells. A previous study has provided a clue that SFTSV NSs may be involved in virus-like or viral RNA synthesis; however, the details remain unclear. Our work described here reveals that SFTSV NSs can downregulate virus-like RNA synthesis in a dose-dependent manner within a cDNA-derived viral RNA synthesis system, i.e., minigenome (−) and minigenome (+) systems based on transfection, superinfection, and luciferase reporter activity determination; meanwhile, NSs also show a weak inhibitory effect on virus replication. By using co-immunoprecipitation (Co-IP) and RT-PCR combined with site-directed mutagenesis, we found that NSs suppress virus-like RNA or virus replication through interacting with N but not with RdRp, and the negative regulatory effect correlates closely with the IB structure it formed but is not associated with its role of antagonizing host innate immune responses. When the cytoplasmic structure of IB formed by SFTSV NSs was deprived, the inhibitory effect of NSs on virus-like RNA synthesis would weaken and even disappear. Similarly, we also evaluated other bandavirus NSs that cannot form IB in neither infected nor transfected cells, and the results showed that the NSs of Heartland bandavirus (HRTV) did not show a significant inhibitory effect on virus-like RNA synthesis within a minigenome system. Our findings provide experimental evidence that SFTSV NSs participate in regulating virus-like or viral RNA synthesis and the negative effect may be due to the NSs–N interaction. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging bunyavirus that causes severe viral hemorrhagic fever and thrombocytopenia syndrome with a fatality rate of up to 30%. No licensed vaccines or therapeutics are currently available for humans. Here, we develop seven monoclonal antibodies (mAbs) against SFTSV surface glycoprotein Gn. Mechanistic studies show that three neutralizing mAbs (S2A5, S1G3, and S1H7) block multiple steps during SFTSV infection, including viral attachment and membrane fusion, whereas another neutralizing mAb (B1G11) primarily inhibits the viral attachment step. Epitope binning and X-ray crystallographic analyses reveal four distinct antigenic sites on Gn, three of which have not previously been reported, corresponding to domain I, domain II, and spanning domain I and domain II. One of the most potent neutralizing mAbs, S2A5, binds to a conserved epitope on Gn domain I and broadly neutralizes infection of six SFTSV strains corresponding to genotypes A to F. A single dose treatment of S2A5 affords both pre- and post-exposure protection of mice against lethal SFTSV challenge without apparent weight loss. Our results support the importance of glycoprotein Gn for eliciting a robust humoral response and pave a path for developing prophylactic and therapeutic antibodies against SFTSV infection. Ren et al. generate a panel of monoclonal antibodies (mAbs) that recognize distinct epitopes on the glycoprotein Gn and neutralize severe fever with thrombocytopenia syndrome virus (SFTSV) by diverse mechanisms. One most potent mAb targeting the Gn domain I provides protection against lethal SFTSV infection in mice. [ABSTRACT FROM AUTHOR]

Background: Severe fever with thrombocytopenia syndrome (SFTS), caused by the Dabie bandavirus (DBV), formerly known as the SFTS virus (SFTSV), is characterized by rapid progression, high morbidity, and mortality. This study aims to analyze the current research status, hotspots, and trends of SFTS since 2009 through bibliometrics, focusing on original research and providing valuable references and inspirations for future basic research, prevention and control of SFTS. Methods: The Web of Science Core Collection (WOSCC) was used to extract global papers on SFTS from 2009 to 2024. VOSviewer and CiteSpace software were also used to process and visualize results. Results: A total of 760 publications relevant to SFTS were reviewed. Among these publications, the most active country, author, and publication type included China, Liu Wei, and original articles, respectively. Among the institutions, the National Institute of Infectious Diseases emerged as the top publisher. The most frequently used keywords were "China," "Bunyavirus," and "person-to-person transmission." The bibliometric analysis reviewed and summarized the research results in the field of SFTS and demonstrated the research trends in the field. In addition, the study revealed the current research hotspots and predicted the future research frontiers and potential challenges in the field of SFTS, which will provide references for further exploring and investigating the SFTS-related mechanisms and inspire new therapeutic strategies. Conclusion: Bibliometric visualization provides an overview of research advances, hotspots, and trends regarding SFTS and consolidates existing knowledge. SFTS research is in a phase of rapid development, and the number of annual publications in the field is growing steadily and rapidly. This is laying the groundwork for further research and providing new ideas for clinicians engaged in SFTS-related therapies and researchers working to improve public health. Currently, researchers are focused on elucidating the biology of SFTS, exploring antibodies, delving into pathogenesis, and investigating specific therapies. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome (SFTS) virus, a tick-borne bunyavirus, causes a severe/fatal disease termed SFTS; however, the viral virulence is not fully understood. The viral non-structural protein, NSs, is the sole known virulence factor. NSs disturbs host innate immune responses and an NSs-mutant SFTS virus causes no disease in an SFTS animal model. The present study reports a novel determinant of viral tropism as well as virulence in animal models, within the glycoprotein (GP) of SFTS virus and an SFTS-related tick-borne bunyavirus. Infection with mutant SFTS viruses lacking the N-linked glycosylation of GP resulted in negligible usage of calcium-dependent lectins in cells, less efficient infection, high susceptibility to a neutralizing antibody, low cytokine production in macrophage-like cells, and reduced virulence in Ifnar-/- mice, when compared with wildtype virus. Three SFTS virus-related bunyaviruses had N-glycosylation motifs at similar positions within their GP and a glycan-deficient mutant of Heartland virus showed in vitro and in vivo phenotypes like those of the SFTS virus. Thus, N-linked glycosylation of viral GP is a novel determinant for the tropism and virulence of SFTS virus and of a related virus. These findings will help us understand the process of severe/fatal diseases caused by tick-borne bunyaviruses. Author summary: Ticks sometimes contain small pathogens in their bodies. Because ticks need blood to survive, upon bloodsucking, the pathogens spread to humans as well as animals and cause diseases in some cases. One such pathogen is the bunyavirus, which includes severe fever with thrombocytopenia syndrome virus, and diseases caused by these viruses are often fatal. Most details of bunyavirus-driven diseases are poorly understood, but a viral protein, NSs, was shown to disturb immune responses in humans. This study reports the discovery and characteristics of a novel virulence factor within another bunyaviral glycoprotein. The novel virulence factor is N-glycosylated modification and involves the viral targets for infection. Mutant viruses lacking the modification in the glycoprotein had limited infection potential in cell culture experiments and weakened virulence in animal experiments. Our findings will help us understand bunyavirus-driven diseases and, hopefully, promote countermeasures against the diseases, leading to safer outdoor activities. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by SFTS bunyavirus (SFTSV), a tick borne bunyavirus. However, Immunohistochemistry of SFTS patients are not well studied. Methods: We obtained multiple of tissues from a fatal case with SFTS, including blood, lungs, kidneys, heart, and spleen. The blood samples were used to isolate the causative agent for detection of viral RNA and further expression of recombinant viral protein as primary antibody. Immunohistochemistry of the heart, lungs, spleen and kidneys was used to characterize the viral antigen in tissue sections. Results: A 79-year-old man, together with his wife, was admitted because of fever. Both patients were diagnosed with SFTS by the positive SFTSV RNA in the blood. The gentleman died of multiple organ failure 8 days after hospitalization. However, his wife recovered and was discharged. Immunohistochemistry indicated that SFTSV antigens were present in all studied organs including the heart, kidney, lung and spleen, of which the spleen presented with the highest amount of SFTSV antigens. The kidney was next while the heart and lungs showed lower amount of SFTSV antigens. Conclusions: SFTSV can direct infect multiple organs, resulting in multiple organ failure and ultimately in an unfavorable outcome. [ABSTRACT FROM AUTHOR]

In our prior investigations, we elucidated the role of the tryptophan-to-tyrosine substitution at the 61st position in the nonstructural protein NSsW61Y in diminishing the interaction between nonstructural proteins (NSs) and nucleoprotein (NP), impeding viral replication. In this study, we focused on the involvement of NSs in replication via the modulation of autophagosomes. Initially, we examined the impact of NP expression levels, a marker for replication, upon the infection of HeLa cells with severe fever thrombocytopenia syndrome virus (SFTSV), with or without the inhibition of NP binding. Western blot analysis revealed a reduction in NP levels in NSsW61Y-expressing conditions. Furthermore, the expression levels of the canonical autophagosome markers p62 and LC3 decreased in HeLa cells expressing NSsW61Y, revealing the involvement of individual viral proteins on autophagy. Subsequent experiments confirmed that NSsW61Y perturbs autophagy flux, as evidenced by reduced levels of LC3B and p62 upon treatment with chloroquine, an inhibitor of autophagosome–lysosome fusion. LysoTracker staining demonstrated a decrease in lysosomes in cells expressing the NS mutant compared to those expressing wild-type NS. We further explored the mTOR-associated regulatory pathway, a key regulator affected by NS mutant expression. The observed inhibition of replication could be linked to conformational changes in the NSs, impairing their binding to NP and altering mTOR regulation, a crucial upstream signaling component in autophagy. These findings illuminate the intricate interplay between NSsW61Y and the suppression of host autophagy machinery, which is crucial for the generation of autophagosomes to facilitate viral replication. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a novel tick-borne viral pathogen that causes severe fever with thrombocytopenia syndrome (SFTS). The disease was initially reported in central and eastern China, then later in Japan and South Korea, with a mortality rate of 13–30%. Currently, no vaccines or effective therapeutics are available for SFTS treatment. In this study, three monoclonal antibodies (mAbs) targeting the SFTSV envelope glycoprotein Gn were obtained using the hybridoma technique. Two mAbs recognized linear epitopes and did not neutralize SFTSV, while the mAb 40C10 can effectively neutralized SFTSV of different genotypes and also the SFTSV-related Guertu virus (GTV) and Heartland virus (HRTV) by targeting a spatial epitope of Gn. Additionally, the mAb 40C10 showed therapeutic effect in mice infected with different genotypes of SFTSV strains against death by preventing the development of lesions and by promoting virus clearance in tissues. The therapeutic effect could still be observed in mice infected with SFTSV which were administered with mAb 40C10 after infection even up to 4 days. These findings enhance our understanding of SFTSV immunogenicity and provide valuable information for designing detection methods and strategies targeting SFTSV antigens. The neutralizing mAb 40C10 possesses the potential to be further developed as a therapeutic monoclonal antibody against SFTSV and SFTSV-related viruses. Author summary: Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) is a tick-borne pathogen that causes severe illness known as SFTS. This disease has become a major health concern, particularly in China, Japan and South Korea, with a high mortality rate. Regrettably, there are currently no vaccines or effective treatments available for this disease. To address this critical gap, we developed three monoclonal antibodies (mAbs) targeting a specific region of the SFTSV glycoprotein. Among these mAbs, one, named 40C10, exhibited remarkable neutralizing activity against SFTSV as well as related viruses such as HRTV and GTV. It provided complete protection against disease and death in mice even when administered days after viral exposure. These findings are promising and suggest that mAb 40C10 has potential as a therapeutic option against SFTSV. This work is a significant step towards meeting the urgent need for effective treatments for SFTS. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne viral disease caused by the SFTS virus (Dabie bandavirus), which has become a substantial risk to public health. No specific treatment is available now, that calls for an effective vaccine. Given this, we aimed to develop a multi-epitope DNA vaccine through the help of bioinformatics. The final DNA vaccine was inserted into a special plasmid vector pVAX1, consisting of CD8+ T cell epitopes, CD4+ T cell epitopes and B cell epitopes (six epitopes each) screened from four genome-encoded proteins——nuclear protein (NP), glycoprotein (GP), RNA-dependent RNA polymerase (RdRp), as well as nonstructural protein (NSs). To ascertain if the predicted structure would be stable and successful in preventing infection, an immunological simulation was run on it. In conclusion, we designed a multi-epitope DNA vaccine that is expected to be effective against Dabie bandavirus, but in vivo trials are needed to verify this claim. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome (SFTS) virus, recently named Bandavirus dabieense, belongs to the genus Bandavirus of family Phenuiviridae, and it causes SFTS in humans with clinical symptoms including fever, thrombocytopenia, gastrointestinal symptoms, and leukocytopenia. However, there are few reports on the pathogenesis of SFTSV in animals. This study first isolated the SFTSV strain SD22-2 from sick-farmed mink. Viral metagenomics was used to detect SFTSV nucleotide in the clinical specimens obtained from symptomatic minks. Then, we isolated the virus using Vero and DH82 cells, and Real-Time Quantitative PCR (RT-qPCR), indirect immunofluorescence assay, transmission electron microscopy, and Western blotting identified it. Meanwhile, phylogenetic analysis based on partial L, M, and S segment sequences indicated that the mink-origin SFTSV strain SD22-2 belonged to genotype D and was genetically close to the HB2016-003 strain isolated from humans. Taken together, we isolated and identified an SFTSV from farmed mink that may be the reservoir hosts of SFTSV. We should pay more attention to farmed minks and biosecurity practices, and active surveillance at fur farms must be reviewed and enhanced. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome (SFTS) is a recently identified infectious ailment triggered by a new strain of bunyavirus. It is distinguished by elevated fatality rates, ranging from 12 % to 30 %. The mechanism underlying the development of severe illness caused by SFTS bunyavirus (SFTSV) is not yet fully understood. To evaluate the role of the TLR2 receptor pathway in regulating Treg function in the progression of SFTS disease and possible mechanisms, sequential serum samples from 29 patients with SFTS (15 mild, 14 severe cases) were examined. Flow cytometry was employed to scrutinize the phenotypic and functional characteristics of TLR2 expression on circulating CD4 T cells, CD8 T cells, and Tregs. In all admitted patients, the evaluation of correlations between the frequencies of the aforementioned cells and SFTS index (SFTSI) was conducted. For SFTS, the levels of TLR2 on CD4 T cells and Tregs were significantly heightened when compared to those in healthy subjects. Additionally, the expression of TLR2 on Tregs exhibited a positive correlation with Ki-67 expression in Tregs and the severity of disease. Additionally, compared with those in uninfected controls, the expression levels of NF-κB in Tregs were significantly increased. Collectively, Tregs may be activated and proliferate through the stimulation of the TLR2/NF-кB pathway in reaction to SFTSV infection.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease caused by the newly discovered SFTS Bunyavirus, and there have been no case reports of SFTS patients presenting with hemophagocytic lymphohistiocytosis (HLH) in the English literature. We report a case of SFTS presenting with HLH in a 73-year-old immunocompetent male farmer. Although the patient had poor prognostic factors for SFTS, such as old age and central nervous system symptoms, he recovered fully with supportive care. [ABSTRACT FROM AUTHOR]

Tick-borne virus detection in livestock and slaughterhouse animals has recently surged in the United States and Europe. Although cases of patients with tick-borne illnesses have been reported in Korea, food contamination from tick-borne viruses has yet to be investigated. Therefore, this study investigated severe fever with thrombocytopenia syndrome virus (SFTSV), tick-borne encephalitis virus (TBEV), and Crimean–Congo hemorrhagic fever virus (CCHFV) prevalence in meat and dairy products. A total of 628 products were collected from a Korean retail market during 2021–2022, including 195 beef, 130 goats, 90 lambs, 61 pork, 50 chicken, and 38 commercial cheese samples. In addition, 64 raw cow milk samples were collected from a ranch in Anseong-si, Gyeonggi-do, from 2021 to 2022. Real-time reverse transcription-polymerase chain reaction (RT-PCR), nested reverse transcription polymerase chain reaction (RT-nPCR), virus cultivation, and sequence analysis were conducted. SFTSV was detected in 1.53% (3/195) beef and 0.76% (1/130) goat meat samples with a low Ct value titer from 33.18 to 38.60. In contrast, SFTSV was neither detected in lamb, pork, chicken, raw milk, or cheese samples nor were TBEV and CCHFV detected in any of the tested samples. Although no existing cases or studies have indicated SFTSV transmittance through food, this study confirmed SFTSV genotype B RNA in SFTSV-positive meat samples. Therefore, monitoring for and evaluating SFTSV-contaminated meat products must be investigated in future studies. [ABSTRACT FROM AUTHOR]

Wuxiang virus (WUXV) is the first sandfly-borne Phlebovirus isolated from Phlebotomus chinensis collected in China and has been established as a consistent viral presence in the local sandfly populations of both Wuxiang County and Yangquan City. However, its distribution in the Shanxi Province remains unclear. In this study, three novel WUXV strains were isolated from sandflies collected from Jiexiu City, Shanxi Province, China, in 2022. Subsequently, whole-genome sequences of these novel strains were generated using next-generation sequencing. The open reading frame (ORF) sequences of the WUXV strains from the three locations were subjected to gene analysis. Phylogenetic analysis revealed that WUXV belongs to two distinct clades with geographical differences. Strains from Wuxiang County and Yangquan City belonged to clade 1, whereas strains from Jiexiu City belonged to clade 2. Reassortment and recombination analyses indicated no gene reassortment or recombination between the two clades. However, four reassortments or recombination events could be detected in clade 1 strains. By aligning the amino acid sequences, eighty-seven mutation sites were identified between the two clades, with seventeen, sixty, nine, and one site(s) in the proteins RdRp, M, NSs, and N, respectively. Additionally, selection pressure analysis identified 17 positively selected sites across the entire genome of WUXV, with two, thirteen, one, and one site(s) in the proteins RdRp, M, NSs, and N, respectively. Notably, sites M-312 and M-340 in the M segment not only represented mutation sites but also showed positive selective pressure effects. These findings highlight the need for continuous nationwide surveillance of WUXV. [ABSTRACT FROM AUTHOR]

Copyright of China Tropical Medicine is the property of China Tropical Medicine Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease discovered in China in 2009. The purpose of this study was to describe the spatiotemporal distribution of SFTS and to identify its environmental influencing factors and potential high-risk areas in Shandong Province, China. Methods: Data on the SFTS incidence from 2010 to 2021 were collected. Spatiotemporal scan statistics were used to identify the time and area of SFTS clustering. The maximum entropy (MaxEnt) model was used to analyse environmental influences and predict high-risk areas. Results: From 2010 to 2021, a total of 5705 cases of SFTS were reported in Shandong. The number of SFTS cases increased yearly, with a peak incidence from April to October each year. Spatiotemporal scan statistics showed the existence of one most likely cluster and two secondary likely clusters in Shandong. The most likely cluster was in the eastern region, from May to October 2021. The first secondary cluster was in the central region, from May to October 2021. The second secondary cluster was in the southeastern region, from May to September 2020. The MaxEnt model showed that the mean annual wind speed, NDVI, cattle density and annual cumulative precipitation were the key factors influencing the occurrence of SFTS. The predicted risk map showed that the area of high prevalence was 28,120 km2, accounting for 18.05% of the total area of the province. Conclusions: The spatiotemporal distribution of SFTS was heterogeneous and influenced by multidimensional environmental factors. This should be considered as a basis for delineating SFTS risk areas and developing SFTS prevention and control measures. [ABSTRACT FROM AUTHOR]

Background: Infectious diseases transmitted by wild animals are major threats to public health. This study aimed to investigate the potential of rescued wild animals that died of unknown causes as reservoirs of infectious agents. From 2018 to 2019, 121 dead wild animals (55 birds and 66 mammals) were included in this study. All wild animals died during treatment after anthropogenic events. After deaths of animals, necropsies were performed and trachea, lungs, large intestine (including stool), and spleen were collected to determine causes of deaths. A high-throughput screening (HTS) quantitative polymerase chain reaction (qPCR) designed to detect 19 pathogens simultaneously against 48 samples in duplicate was performed using nucleic acids extracted from pooled tissues and peripheral blood samples. If positive, singleplex real-time PCR was performed for individual organs or blood samples. Results: The HTS qPCR showed positive results for Campylobacter jejuni (10/121, 8.3%), Campylobacter coli (1/121, 0.8%), Mycoplasma spp. (78/121, 64.5%), and Plasmodium spp. (7/121, 5.7%). Singleplex real-time PCR confirmed that C. jejuni was detected in the large intestine but not in the blood. C. coli was only detected in the large intestine. Mycoplasma spp. were detected in all organs, having the highest proportion in the large intestine and lowest in the blood. Plasmodium spp. was also detected in all organs, with proportions being were similar among organs. Conclusions: This study shows that wild animals can become carriers of infectious agents without showing any clinical symptoms. [ABSTRACT FROM AUTHOR]

Background: Severe fever with thrombocytopenia syndrome (SFTS), which was first discovered in China in 2009, is an infectious disease with a high mortality rate, particularly in East Asia. This study aimed to investigate the epidemiological and clinical characteristics and risk factors for mortality by analyzing SFTS cases accumulated for up to ten years in Jeju, Korea. Materials and Methods: Medical records of patients diagnosed with SFTS between March 2013 and August 2022 at a tertiary hospital in Jeju were analyzed retrospectively. We investigated data of patients with SFTS on the epidemiologic and clinical characteristics, laboratory findings, and administered treatments and compared the differences between fatal and non-fatal groups. Results: We enrolled 91 SFTS-confirmed patients. The median age of patients was 62 years, and the fatality rate increased with age (P = 0.004). Fever was the most common symptom (84.6%), and diarrhea (37.4%) was also present in some cases. The overall fatality rate was 10.9%. Dyspnea (20.0% vs. 0.0%, P = 0.009) and changes in mental status (70.0% vs. 11.0%, P <0.001) were more frequent in fatal cases. Risk factor assessment revealed that a high aspartate aminotransferase /alanine aminotransferase ratio (odds ratio [OR]: 39.568, 95% confidence interval [CI]: 1.479 – 1,058.639, P = 0.028) and elevated total bilirubin levels (OR: 53.037, 95% CI: 1.064 - 2,643.142, P = 0.046) were also significantly associated with fatal cases. Plasma exchange (40.7%) was the most commonly administered treatment. Conclusion: SFTS has a high mortality rate; therefore, awareness of SFTS must be raised among physicians and citizens living in tick-inhabited areas, such as Jeju. [ABSTRACT FROM AUTHOR]

An online survey was conducted in Korea to identify the unmet medical needs of people living with human immunodeficiency virus (HIV) (PLWH). Participants (n = 105) were mostly male (93.3%), aged >40 years (75.2%), and treated for ≥6 years post-diagnosis (61.9%). Most PLWH (71.4%) were very satisfied/satisfied with their HIV management. Areas of concern were quality of life (QoL) and mental health. Characteristics of a long-term therapeutic agent were ‘low risk of resistance’, ‘high long-term viral suppression efficacy’, and ‘high degree of safety’. Pre-consultation QoL and mental health screening would be beneficial for the long-term success of HIV management. [ABSTRACT FROM AUTHOR]

Background: Severe fever with thrombocytopenia syndrome (SFTS) is a common tick-borne, natural focal disease. SFTS virus (SFTSV) transmission can occur between family members through close contact with an infected patient. In this study, we explored the possible transmission route of an outbreak cluster in east China. Method: A case-control study was carried out to analyze the potential risk factors for person-to-person transmission. Bunia virus was detected by IgM antibody, enzyme-linked immunosorbent assay, and reverse transcription polymerase chain reaction. Chi-square, univariate, and multivariate analyses were performed to calculate the association of possible risk factors for SFTSV transmission. Results: Two patients had a clear history of blood and aerosols contact, and one may be exposed to aerosols in a closed environment. Five close contacts of the Index patient were IgM-positive and three were IgM and SFTSV RNA positive. Exposure to a poorly ventilated space where the corpse was stored (χ2 = 5.49, P = 0.019) and contact with the Index patient's contaminated items (χ2 = 15.77, P < 0.001) significantly associated with SFTSV infection. Conclusion: We suspect that the cluster outbreak was possibly a person-to-person transmission of SFTSV, which may have been transmitted by directly contacting with blood of SFTS patient. The propagation of aerosols in closed environments is also an undeniable transmission. [ABSTRACT FROM AUTHOR]

Severe Fever with Thrombocytopenia Syndrome (SFTS), caused by Dabie bandavirus (SFTSV), is an emerging infectious disease first identified in China. Since its discovery, infections have spread throughout East Asian countries primarily through tick bites but also via transmission between animals and humans. The expanding range of ticks, the primary vectors for SFTSV, combined with migration patterns of tick-carrying birds, sets the stage for the global spread of this virus. SFTSV rapidly evolves due to continuous mutation and reassortment; currently, no approved vaccines or antiviral drugs are available. Thus, the threat this virus poses to global health is unmistakable. This review consolidates the most recent research on SFTSV, including its molecular characteristics, transmission pathways through ticks and other animals, as well as the progress in antiviral drug and vaccine development, encompassing animal models and clinical trials. [ABSTRACT FROM AUTHOR]

BACKGROUND Severe fever with thrombocytopenia syndrome (SFTS) is a new infectious disease characterised by thrombocytopenia and a bleeding phenomenon. The infection can be transmitted by contact with the athlete patient's blood and/or blood-contaminated secretions. In clinical settings, nursing care of these athlete patients is inherently challenging owing to the risk of transmission of infection. CASE SUMMARY We report a rare case of an SFTS athlete patient who developed an injection-site haematoma (3 cm × 3 cm) with local oozing 72 hours after intradermal injection of piperacillin sodium and tazobactam sodium. The treatment was aimed at stopping the bleeding, resolution of haematoma to relieve pain and prevention of infection to medical personnel. The athlete patient was isolated in a single room. An elastic bandage was applied locally to stop the bleeding, and the forearm was elevated. After the cessation of bleeding, freshly-cut thin potato slices were applied externally and wrapped with plastic wrap during the day, whereas 3M hydrophilic dressing was applied externally at night. With this treatment method (new triple therapy), the athlete patient's haematoma dissipated and the skin healed after one week. CONCLUSION The novel triple therapy for post-injection haematoma in an athlete patient with SFTS was found to be convenient, safe and effective. [ABSTRACT FROM AUTHOR]

Currently, there are no commercial vaccines or therapeutics against severe fever with thrombocytopenia syndrome (SFTS) virus. This study explored an engineered Salmonella as a vaccine carrier to deliver a eukaryotic self-mRNA replicating vector, pJHL204. This vector expresses multiple SFTS virus antigenic genes for the nucleocapsid protein (NP), glycoprotein precursor (Gn/Gc), and nonstructural protein (NS) to induce host immune responses. The engineered constructs were designed and validated through 3D structure modeling. Western blot and qRT-PCR analyses of transformed HEK293T cells confirmed the delivery and expression of the vaccine antigens. Significantly, mice immunized with these constructs demonstrated a cell-mediated and humoral response as balanced Th1/Th2 immunity. The JOL2424 and JOL2425 delivering NP and Gn/Gc generated strong immunoglobulin IgG and IgM antibodies and high neutralizing titers. To further examine the immunogenicity and protection, we utilized a human DC-SIGN receptor transduced mouse model for SFTS virus infection by an adeno-associated viral vector system. Among the SFTSV antigen constructs, the construct with full-length NP and Gn/Gc and the construct with NP and selected Gn/Gc epitopes induced robust cellular and humoral immune responses. These were followed by adequate protection based on viral titer reduction and reduced histopathological lesions in the spleen and liver. In conclusion, these data indicate that recombinant attenuated Salmonella JOL2424 and JOL2425 delivering NP and Gn/Gc antigens of SFTSV are promising vaccine candidates that induce strong humoral and cellular immune responses and protection against SFTSV. Moreover, the data proved that the hDC-SIGN transduced mice as a worthy tool for immunogenicity study for SFTSV. [ABSTRACT FROM AUTHOR]

Sever fever with thrombocytopenia syndrome (SFTS) is a new infectious disease that has emerged in recent years and is widely distributed, highly contagious, and lethal, with a mortality rate of up to 30%, especially in people with immune system deficiencies and elderly patients. SFTS is an insidious, negative-stranded RNA virus that has a major public health impact worldwide. The development of a vaccine and the hunt for potent therapeutic drugs are crucial to the prevention and treatment of Bunyavirus infection because there is no particular treatment for SFTS. In this respect, investigating the mechanics of SFTS–host cell interactions is crucial for creating antiviral medications. In the present paper, we summarized the mechanism of interaction between SFTS and pattern recognition receptors, endogenous antiviral factors, inflammatory factors, and immune cells. Furthermore, we summarized the current therapeutic drugs used for SFTS treatment, aiming to provide a theoretical basis for the development of targets and drugs against SFTS. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease, which is caused by severe fever with thrombocytopenia syndrome virus (SFTSV) with high fatality. Recently, the incidence of SFTS increased obviously in Jiangsu Province. However, the systematic and complete analysis of spatiotemporal patterns and clusters coupled with epidemiological characteristics of SFTS have not been reported so far. Methods: Data on SFTS cases were collected during 2011–2021. The changing epidemiological characteristics of SFTS were analyzed by adopting descriptive statistical methods. GeoDa 1.18 was applied for spatial autocorrelation analysis, and SaTScan 10.0 was used to identify spatio-temporal clustering of cases. The results were visualized in ArcMap. Results: The annual incidence of SFTS increased in Jiangsu Province from 2011 to 2021. Most cases (72.4%) occurred during May and August with the obvious peak months. Elderly farmers accounted for most cases, among which both males and females were susceptible. The spatial autocorrelation and spatio-temporal clustering analysis indicated that the distribution of SFTS was not random but clustered in space and time. The most likely cluster was observed in the western region of Jiangsu Province and covered one county (Xuyi county) (Relative risk = 8.18, Log likelihood ratio = 122.645, P < 0.001) located in southwestern Jiangsu Province from January 1, 2017 to December 31, 2021. The Secondary cluster also covered one county (Lishui county) (Relative risk = 7.70, Log likelihood ratio = 94.938, P < 0.001) from January 1, 2017 to December 31, 2021. Conclusions: The annual number of SFTS cases showed an increasing tendency in Jiangsu Province from 2011 to 2021. Our study elucidated regions with SFTS clusters by means of ArcGIS in combination with spatial analysis. The results demonstrated solid evidences for the orientation of limited sanitary resources, surveillance in high-risk regions and early warning of epidemic seasons in future prevention and control of SFTS in Jiangsu Province. [ABSTRACT FROM AUTHOR]

Background: There are a few models for predicting the outcomes of patients with severe fever with thrombocytopenia syndrome (SFTS) based on single-center data, but clinicians need more reliable models based on multicenter data to predict the clinical outcomes and effectiveness of drug therapy. Methodology/Principal findings: This retrospective multicenter study analyzed data from 377 patients with SFTS, including a modeling group and a validation group. In the modeling group, the presence of neurologic symptoms was a strong predictor of mortality (odds ratio: 168). Based on neurologic symptoms and the joint indices score, which included age, gastrointestinal bleeding, and the SFTS virus viral load, patients were divided into double-positive, single-positive, and double-negative groups, which had mortality rates of 79.3%, 6.8%, and 0%, respectively. Validation using data on 216 cases from two other hospitals yielded similar results. A subgroup analysis revealed that ribavirin had a significant effect on mortality in the single-positive group (P = 0.006), but not in the double-positive or double-negative group. In the single-positive group, prompt antibiotic use was associated with reduced mortality (7.2% vs 47.4%, P < 0.001), even in individuals without significant granulocytopenia and infection, and early prophylaxis was associated with reduced mortality (9.0% vs. 22.8%, P = 0.008). The infected group included SFTS patients with pneumonia or sepsis, while the noninfected group included patients with no signs of infection. The white blood cell count and levels of C-reactive protein and procalcitonin differed significantly between the infection and non-infection groups (P = 0.020, P = 0.011, and P = 0.003, respectively), although the absolute difference in the medians were small. Conclusions/Significance: We developed a simple model to predict mortality in patients with SFTS. Our model may help to evaluate the effectiveness of drugs in these patients. In patients with severe SFTS, ribavirin and antibiotics may reduce mortality. Author summary: Severe fever with thrombocytopenia syndrome (SFTS) was first reported in 2011 and 11.2–30% of patients die of multiple organ failure. Previous prognostic models for SFTS are mostly based on single-center data and lack validation. Moreover, the drug efficacy of ribavirin and gamma globulin is controversial. Here, we developed a simple model for predicting the mortality and help to evaluate the effectiveness of drugs in patients with SFTS. In this study, the data of three hospitals were used to establish and verify the model. Based on neurologic symptoms and the joint indices score, which considered age, gastrointestinal bleeding, and SFTSV RNA, patients were divided into double-positive, single-positive, and double-negative groups, which had mortality rates of 79.3%, 6.8%, and 0% in the modeling groups, respectively. Validation yielded similar results. Subgroup analysis revealed that ribavirin had a significant effect on mortality in the single-positive group but not in the other two groups. In the single-positive group, prompt antibiotic use was associated with reduced mortality, even in individuals without significant granulocytopenia and infection, and early prophylaxis was associated with reduced mortality. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne pathogen for which approved therapeutic drugs or vaccines are not available. We previously developed a recombinant vesicular stomatitis virus-based vaccine candidate (rVSV-SFTSV) by replacing the original glycoprotein with Gn/Gc from SFTSV, which conferred complete protection in a mouse model. Here, we found that two spontaneous mutations, M749T/C617R, emerged in the Gc glycoprotein during passaging that could significantly increase the titer of rVSV-SFTSV. M749T/C617R enhanced the genetic stability of rVSV-SFTSV, and no further mutations appeared after 10 passages. Using immunofluorescence analysis, we found that M749T/C617R could increase glycoprotein traffic to the plasma membrane, thus facilitating virus assembly. Remarkably, the broad-spectrum immunogenicity of rVSV-SFTSV was not affected by the M749T/C617R mutations. Overall, M749T/C617R could enhance the further development of rVSV-SFTSV into an effective vaccine in the future. [ABSTRACT FROM AUTHOR]