Search Results (73)

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne bunyavirus that causes a severe viral hemorrhagic fever (SFTS), with a very high case mortality rate, expanding epidemic areas, and increasing incidence. Due to the lack of an effective drug or vaccine for SFTS, reducing the incidence and mortality of SFTS primarily relies on decreasing the density of ticks and the number of their host animals. However, which tick species and vertebrate animal serve as the major reservoir and animal host of SFTSV are not clearly understood. In May of 2023 and June of 2024, we collected 2437 ticks from domesticated animals and grassland in Suizhou City, a prefecture of Hubei Province in central China. A total of 195 domesticated animal blood samples were collected, including 152 goats, 26 cattle, and 17 dogs. Ticks were grouped for RNA extraction according to their life stages and feeding status. RNA from each animal’s blood and each group of ticks was extracted with an RNA extraction kit and tested for SFTSV with RT-PCR. Ticks were classified according to morphology, and representative ticks of each stage were confirmed with PCR amplification and DNA sequencing of the mitochondrial 16S RNA gene. Among the collected ticks, the majority were from goats (72.7%, 1772/2437), and Haemaphysalis longicornis was predominant, accounting for 99.47% (2425/2437), and other tick species were very rare, with 0.45% (11/2437) Rhipicephalus microplus, and 0.04% (1/2437) H. flava and Ixodes sinensis, respectively. We found SFTSV RNA in H. longicornis ticks with a minimum infection rate of 0.17% (4/2424) and in one goat (0.66%,1/152). In summary, we demonstrated that the H. longicornis tick is positive for SFTSV and that the goat is the major host of Haemaphysalis longicornis in Suizhou, central China. Our study suggests that controlling ticks on goats may play an important role in preventing SFTSV infection in China. Full article

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne bunyavirus with a mortality rate of up to 30%. There is no specific treatment for SFTSV. This article systematically reviews the progress of major anti-SFTSV drugs. The nucleotide analogues (favipiravir, 4′-fluorouridine diphosphate prodrug VV261) have shown clinical potential. Calcium channel blockers (nifedipine, etc.) block virus invasion by inhibiting calcium influx. Monoclonal antibody (S2A5/SNB02) has achieved targeted therapy, and SNB02 nanoantibody has entered clinical trials. However, many candidate agents predominantly focus on a single target, such as viral RdRp or host calcium channels, which makes it difficult to block the entire viral replication cycle and may accelerate the accumulation of resistant mutations. In addition, the low bioavailability of small-molecule drugs, the obstacles to industrial-scale production of antibody-based therapies, and the lack of Phase III clinical evidence severely restrict their clinical translation. Future research should focus on exploring viral replication mechanisms, developing drugs against key viral proteins, and designing multi-target combination therapies and novel drug delivery systems. Full article

Background: Severe fever with thrombocytopenia syndrome virus (SFTSV) is a highly pathogenic bunyavirus with a high case-fatality ratio for which there is no approved vaccine. Studies have assessed different vaccine technologies. However, few studies have yet assessed the immunogenicity of heterologous prime-boost regimens. Methods: Here, we compare a lipid nanoparticle (LNP)-encapsulated nucleoside-modified mRNA-based vaccine encoding the SFTSV glycoproteins, Gn and Gc, to our recently described recombinant VSV SFTSV (rVSV-SFTSV) vaccine in single dose, homologous, and heterologous prime-boost regimens in mice. Results: We show that all regimens protect from pathogenic SFTSV challenge and elicit strong long-lasting antibody responses. Furthermore, strong cellular immunity is elicited by mRNA-LNP immunizations and by heterologous immunization with an rVSV-SFTSV prime and mRNA-LNP boost. Cellular responses robustly polarized towards a type 1 response, characterized by high levels of IFNγ, TNFα, and IL-2. Immunization with mRNA led to a mixed type 1/type 2 immune response, as determined by antibody isotypes IgG1 and IgG2c. We found that homologous immunization leads to stronger antibody responses while heterologous immunization drives a slightly stronger cellular response. Conclusions: Taken together, the vaccine platforms described here represent strong vaccine candidates for further development. Full article

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease caused by the SFTS virus (SFTSV). A rapid and cost-effective point-of-care testing detection system is important for the early diagnosis of SFTS. Herein, we developed a ready-to-use dried reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for the direct detection of SFTSV in clinical samples. The assay enables simple, RNA-extraction-free detection using heat-treated serum or plasma, followed by a 30 min incubation at 65 °C. The results are visually interpreted through the color emitted, which can be observed under LED light. The established assay demonstrated detection sensitivity for SFTSV at 10⁴ copies/µL and was effective in identifying infections in cats. Despite being less sensitive than real-time RT-PCR, this dried RT-LAMP method offers a rapid, cost-effective alternative suitable for point-of-care use, particularly in remote or resource-limited settings. The simplified workflow and visual readout make it a practical tool for the early detection and daily surveillance of SFTSV in animals. Full article

Severe fever with thrombocytopenia syndrome (SFTS), an emerging infectious tick-borne viral disease, is increasingly affecting human beings worldwide. SFTS monitoring has been carried out since 2010 in mainland China. Since 2022, an increase in local cases has been noted in the central coastal plain region of Hebei Province. This study aimed to identify the endemic region in the central coastal plain region by epidemiological characteristics, antibody surveillance and molecular characterization. Case data were obtained from the Chinese Disease Control and Prevention Information System. Serum samples from suspected or clinically diagnosed cases, the indigenous healthy population and native domesticated animals were collected for laboratory tests, along with ticks in the central coastal plain region of Hebei Province, China. The local cases were mainly distributed in Cangzhou City, located at the central coastal plain region of Hebei Province. The 0.68% of IgM antibody detection rate and 1.71% of IgG antibody detection rate in this study showed the potential existence of subclinical or mild infections in Cangzhou. Phylogenetic analysis indicated that all sequences from patients, ticks and sheep clustered within the F subtype, exhibiting a close evolutionary relationship and the possible circulation of SFTSV having established among animal hosts and ticks in Cangzhou. These findings first identify the natural focus of SFTSV in the central plain region of Hebei Province, highlighting enhanced surveillance measures for preventing and controlling SFTSV. Full article

Background: Severe fever with thrombocytopenia syndrome virus (SFTSV) is a novel tick-borne bunyavirus, causing the hemorrhagic infectious disease of SFTS, with a case fatality rate up to 30% due to the absence of effective therapeutic interventions. Therefore, it is urgent to develop safe and effective therapeutic drugs to control this viral hemorrhagic fever. Methods: The activity of verteporfin (VP), screened from an FDA-approved drugs library, against SFTSV, was systematically evaluated in Huh7 cells in a wide range of concentrations. We performed time-of-addition experiments with VP, along with binding, endocytosis, and membrane fusion assays, to determine which part of the SFTSV life cycle VP has its effect on. The potential targets of VP were detected by a drug affinity responsive target stability (DARTS) assay. Results: VP exhibited a potent anti-SFTSV activity by blocking the initial viral binding to the target cells during viral entry via significantly inducing the degradation of the viral Gn protein. Conclusions: The VP-induced inhibition of SFTSV binding, the first step of viral invasion, suggested that VP might be an ideal and potent anti-SFTSV agent due to its prophylaxis and therapeutic effects on viral infection. Full article

Theileriosis is considered an economically important disease that may decrease productivity and cause a high mortality rate in livestock. Only a few studies have reported Theileria spp., such as T. sergenti and T. buffeli, in recent decades in Taiwan. In the present study, 401 ticks have been collected on Orchid Island in June 2022 and April 2023. Our environmental investigation for SFTSV unintentionally discovered T. luwenshuni in Haemaphysalis mageshimaensis on Orchid Island via PCR. The PCR products were sequenced, and the detected 18S rRNA gene sequences shared a 99.65–99.93% identity with T. luwenshuni sequences from ticks and ruminants in Myanmar and China. Despite the difficulty in clarifying the source of T. luwenshuni within neighboring regions, our findings provide an updated distribution of T. luwenshuni in Asia. This is not only the first time that T. luwenshuni was found in H. mageshimaensis but also the first report of T. luwenshuni on Orchid Island, Taiwan. Our study indicates that ruminants may be at risk of infection. Therefore, further investigations are needed to determine the distribution of T. luwenshuni among ruminants on Orchid Island and in Taiwan. Full article

Arboviruses pose significant public health challenges globally, particularly in Pakistan, where deforestation, climate change, urbanization, inadequate sanitation, and natural disasters have all contributed to the spread of mosquito-borne flavivirus diseases like dengue fever. The lack of a thorough national surveillance system has made it difficult to determine the extent and distribution of these diseases. Concern has been raised by recent outbreaks of West Nile virus (WNV) and chikungunya (CHIKV) epidemics, which may lead to Zika virus (ZIKV) outbreaks in the future. Additionally, hospital-based surveillance has detected the Japanese encephalitis virus (JEV) in the region. Evidence also points to the presence of additional arboviruses in healthy populations, such as the Karshi virus (KSV), Tamdy virus (TAMV), Crimean–Congo hemorrhagic fever virus (CCHFV), and severe fever with thrombocytopenia syndrome virus (SFTSV). This review aims to address the risk factors linked to these diseases, provide specific policy recommendations for efficient disease prevention and control, and describe the epidemiological trends of these diseases in Pakistan while emphasizing the critical need for improved surveillance and thorough epidemiological investigations. Full article

The prevalence of SFTS is becoming increasingly widespread and is expected to become a significant security issue. The article discusses the prevalence regions and genetic differences in two SFTSV lineages, so as to provide a scientific data basis for the clinical control and prevention of fever with thrombocytopenia syndrome. The literature involving SFTSV patients from 2009 to 2023 and SFTSV complete genome sequences uploaded by NCBI were collected and sorted out, based on time and SFTSV lineage division, we analyzed viral gene sequence. SFTSV patient data were continuously reported from 2009 to 2023, involving five countries including China, South Korea, Japan, Thailand, and Vietnam. There are obvious lineage and host divisions between the SFTSV lineages prevalent in China and abroad. The sources of B-lineage SFTSV samples are mainly concentrated in South Korea, Japan, and the middle and lower reaches of Hubei or Zhejiang in China, with half of the samples coming from humans and half from animals, and the F series SFTSV samples were mainly collected from provinces such as Anhui and Henan in China, with the main source being human patients. The F-lineage SFTSV is the highest proportion in the middle and upper provinces in China. The B lineage has recently appeared in Zhejiang and Taiwan and is prevalent abroad. Using prediction software based on molecular structure prediction technology, analyze the differences between the B and F lineages of SFTSV through prediction methods such as nucleotide mutations, gene recombination, mutation sites, and evolution rates. Conclusively, the differences in SFTSV between B and F lineages may be related to gene recombination of M and L fragments, it was also found that the B lineage had a lower recombination rate and mutation rate than the F lineage, and the evolutionary rate was prominently different. Comparative analysis of the differences in two SFTSV lineage genes could further understand the epidemic status of SFTSV and provide help and more insights for the prevention of the spread of specific types of SFTSV. Full article

H. longicornis is used as an experimental animal model for the study of three-host ticks due to its special life cycle and easy maintenance in the laboratory and in its reproduction. The life cycle of H. longicornis goes through a tightly regulated life cycle to adapt to the changing host and environment, and these stages of transition are also accompanied by proteome changes in the body. Here, we used the isobaric tags for a relative and absolute quantification (iTRAQ) technique to systematically describe and analyze the dynamic expression of the protein and the molecular basis of the proteome of H. longicornis in seven differential developmental stages (eggs, unfed larvae, engorged larvae, unfed nymphs, engorged nymphs unfed adults, and engorged adults). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of the differentially expressed proteins (DEPs) were used. In our study, A total of 2044 proteins were identified, and their expression profiles were classified at different developmental stages. In addition, it was found that tissue and organ development-related proteins and metabolism-related proteins were involved in different physiological processes throughout the life cycle through the GO and KEGG analysis of DEPs. More importantly, we found that the up-regulated proteins of engorged adult ticks were mainly related to yolk absorption, degradation, and ovarian development-related proteins. The abundance of the cuticle proteins in the unfed stages was significantly higher compared with those of the engorged ticks in the previous stages. We believe that our study has made a significant contribution to the research on H. longicornis, which is an important vector of SFTSV. In this study, we identified changes in the proteome throughout the H. longicornis development, and functional analysis highlighted the important roles of many key proteins in developmental events (ovarian development, the molting process, the development of midgut, the development and degeneration of salivary glands, etc.). The revelation of this data will provide a reference proteome for future research on tick functional proteins and candidate targets for elucidating H. longicornis development and developing new tick control strategies. Full article

No effective vaccines or treatments are currently available for severe fever with thrombocytopenia syndrome (SFTS), a fatal tick-borne infectious disease caused by the SFTS virus (SFTSV). This study evaluated the potential of ¹¹¹In-labeled anti-SFTSV antibodies targeting SFTSV structural proteins as single-photon emission computed tomography (SPECT) imaging agents for the selective visualization of SFTSV-infected sites. This study used nuclear medicine imaging to elucidate the pathology of SFTS and assess its therapeutic efficacy. Immunostaining experiments confirmed that the anti-SFTSV antibody (N-mAb), which targets the N protein, specifically accumulated in SFTSV-infected Vero E6 cells. ¹¹¹In-labeled N-mAb was successfully prepared using a diethylenetriaminepentaacetic acid (DTPA) chelator, resulting in [¹¹¹In]In-DTPA-N-mAb with high radiochemical purity exceeding 95% and a radiochemical yield of 55%. Cell-binding assays using SFTSV-infected Vero E6 cells demonstrated that [¹¹¹In]In-DTPA-N-mAb binding was detectable even without membrane permeabilization, with the binding intensity correlating with infection levels. In vivo studies using SFTSV-infected A129 mice showed high spleen accumulation of [¹¹¹In]In-DTPA-N-mAb (87.5% ID/g), consistent with SFTSV tropism, compared to 12.3% ID/g in mock-infected mice. SPECT/CT imaging clearly revealed high radioactivity in these regions. Although nonspecific accumulation was noted in the liver and spleen, this issue may be mitigated through antibody modifications such as fragmentation or PEGylation. Overall, [¹¹¹In]In-DTPA-N-mAb is a promising imaging agent for non-invasive visualization of SFTSV-infected sites and may aid in elucidating SFTS pathology and assessing therapeutic efficacy. Full article

Background: Severe fever with thrombocytopenia syndrome virus (SFTSV) is a recently emerged tickborne virus in east Asia with over 18,000 confirmed cases. With a high case fatality ratio, SFTSV has been designated a high priority pathogen by the WHO and the NIAID. Despite this, there are currently no approved therapies or vaccines to treat or prevent SFTS. Vesicular stomatitis virus (VSV) represents an FDA-approved vaccine platform that has been considered for numerous viruses due to its low sero-prevalence in humans, ease in genetic manipulation, and promiscuity in incorporating foreign glycoproteins into its virions. Methods: In this study, we developed a recombinant VSV (rVSV) expressing the SFTSV glycoproteins Gn/Gc (rVSV-SFTSV) and assessed its safety, immunogenicity, and efficacy in C57BL/6, Ifnar^−/−, and AG129 mice. Results: We demonstrate that rVSV-SFTSV is safe when given to immunocompromised animals and is not neuropathogenic when injected intracranially into young immunocompetent mice. Immunization of wild type (C57BL/6) and Ifnar^−/− mice with rVSV-SFTSV resulted in high levels of neutralizing antibodies and protection in a lethal SFTSV challenge model. Additionally, passive transfer of sera from immunized Ifnar^−/− mice into naïve animals was protective when given pre- or post-exposure. Finally, we demonstrate that immunization with rVSV-SFTSV cross protects AG129 mice against challenge with the closely related Heartland bandavirus despite negligible neutralizing titers to the virus. Conclusions: Taken together, these data suggest that rVSV-SFTSV is a promising vaccine candidate for SFTSV and Heartland bandavirus with a favorable safety profile. Full article

Severe fever with thrombocytopenia syndrome (SFTS) is an acute febrile illness caused by the SFTS virus (SFTSV). We conducted this study to propose a scientific evidence-based treatment that can improve prognosis through changes in viral load and inflammatory cytokines according to the specific treatment of SFTS patients. This prospective and observational study was conducted at 14 tertiary referral hospitals, which are located in SFTS endemic areas in Korea, from 1 May 2018 to 31 October 2020. Patients of any age were eligible for inclusion if they were polymerase chain reaction positive against SFTSV, or showed a four-fold or higher increase in IgG antibody titers between two serum samples collected during the acute and convalescent phases. On the other hand, patients with other tick-borne infections were excluded. In total, 79 patients were included in the study. The viral load of the group treated with steroids was 3.39, 3.21, and 1.36 log₁₀ RNA copies/reaction at each week since the onset of symptoms, and the viral load in patients treated with plasma exchange was 4.47, 2.60, and 2.00 log₁₀ RNA copies/reaction at each week after symptom onset. The inflammatory cytokines were not reduced effectively by any specific treatment except IVIG for the entire treatment period. Secondary infections according to pathogens revealed four bacterial (26.7%) and one fungal (6.7%) infection in the steroid group. The viral load of SFTSV and inflammatory cytokines cannot be decreased by steroid and plasma exchange treatments. Secondary bacterial infections can occur when steroids are administered for the treatment of SFTS. Therefore, caution should be exercised when choosing treatment strategies for SFTS. Full article

Severe fever with thrombocytopenia syndrome virus (SFTSV), also known as the Dabie Banda virus, is an emerging tick-borne Bunyavirus that causes severe fever with thrombocytopenia syndrome (SFTS). Currently, symptomatic treatment and antiviral therapy with ribavirin and favipiravir are used in clinical management. However, their therapeutical efficacy is hardly satisfactory in patients with high viral load. In this study, we explored the antiviral effects of selective estrogen receptor modulators (SERMs) on SFTSV infection and the antiviral mechanisms of a representative SERM, bazedoxifene acetate (BZA). Our data show that SERMs potently inhibited SFTSV-induced cytopathic effect (CPE), the proliferation of infectious viral particles, and viral RNA replication and that BZA effectively protected mice from lethal viral challenge. The mode of action analysis reveals that BZA exerts antiviral effects during the post-entry stage of SFTSV infection. The transcriptome analysis reveals that GRASLND and CYP1A1 were upregulated, while TMEM45B and TXNIP were downregulated. Our findings suggest that SERMs have the potential to be used in the treatment of SFTSV infection. Full article

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. Full article