Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 1.166
Filter
1.
Sci Rep ; 14(1): 20651, 2024 09 04.
Article in English | MEDLINE | ID: mdl-39232049

ABSTRACT

Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne illness with a notable morality risk that is becoming increasingly prevalent in East Asia (14-36%). Increasing evidence indicates a more direct role of the SFTS virus in renal impairment. However, few studies have explored the risk factors for and clinical outcomes of AKI in patients with SFTS. Therefore, in this study, we aimed to investigate risk factors and outcomes associated with AKI in patients with SFTS. In this retrospective cohort study, we included the data of 53 patients who were diagnosed with SFTS virus infection at Kangwon National University Hospital between 2016 and 2020. We incorporated laboratory data and medical information including comorbidities, complications, and mortality. Baseline characteristics, clinical features, laboratory parameters, and mortality rates of the non-AKI and AKI groups were compared. Patient survival of non-AKI and AKI groups were compared using the Kaplan-Meier method. To identify the population with poor prognosis, Cox regression analysis was used to identify the independent risk factors for in-hospital mortality in patients with SFTS. Of the 53 individuals, 29 (54.7%) were male, with an average age of 66.5 years. Nine patients (15.1%) died of SFTS. Twenty-seven (50.9%) patients exhibited AKI; the average time interval from fever onset to AKI occurrence was 3.6 days. Notably, 24 (88.9%) patients developed AKI within the first week of fever onset. Patients in the AKI group exhibited a significantly higher prevalence of diabetes and were older than those in the non-AKI group. The mortality rate was notably higher (29.6%) in the AKI group than in the non-AKI group (3.8%). Within the AKI cohort, advanced stages (stages 2 and 3) showed a 50% mortality rate, which was significantly higher than the 17.6% mortality rate in patients with stage 1 AKI. Additionally, Kaplan-Meier curves revealed lower survival rates among patients with AKI than among those without AKI (P = 0.017). Cox regression analysis identified leukopenia and elevated serum creatinine levels as significant risk factors for mortality. AKI is a common complication associated with SFTS. Moreover, the mortality rate was significantly higher in the patients who developed AKI than in those who did not. Our findings underscore the pivotal role of AKI as a prognostic marker of disease severity in patients with SFTS.


Subject(s)
Acute Kidney Injury , Severe Fever with Thrombocytopenia Syndrome , Humans , Male , Female , Aged , Acute Kidney Injury/mortality , Acute Kidney Injury/etiology , Acute Kidney Injury/diagnosis , Prognosis , Severe Fever with Thrombocytopenia Syndrome/complications , Retrospective Studies , Middle Aged , Risk Factors , Hospital Mortality , Biomarkers/blood , Aged, 80 and over , Phlebovirus
3.
Nat Commun ; 15(1): 7009, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-39147753

ABSTRACT

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.


Subject(s)
Antibodies, Monoclonal , Antibodies, Neutralizing , Antibodies, Viral , Epitopes , Phlebovirus , Severe Fever with Thrombocytopenia Syndrome , Animals , Phlebovirus/immunology , Mice , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/therapeutic use , Antibodies, Monoclonal/immunology , Antibodies, Viral/immunology , Severe Fever with Thrombocytopenia Syndrome/immunology , Severe Fever with Thrombocytopenia Syndrome/virology , Severe Fever with Thrombocytopenia Syndrome/prevention & control , Humans , Epitopes/immunology , Female , Mice, Inbred BALB C , Viral Envelope Proteins/immunology , Crystallography, X-Ray , Chlorocebus aethiops , Glycoproteins/immunology , Vero Cells
4.
BMC Infect Dis ; 24(1): 765, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39090556

ABSTRACT

BACKGROUND: Since its discovery, severe fever with thrombocytopenia syndrome (SFTS) has been characterized by rapid progression and poor prognosis, and no specific treatment is available. The aim of this study was to investigate the early warning indicators of mortality in SFTS patients. METHODS: This is a retrospective cross-sectional study. The study subjects were patients who were admitted to the hospital with a confirmed diagnosis of SFTS from January 2023 to October 2023, and their clinical symptoms and signs at the time of admission, as well as the laboratory indexes of the first blood collection after admission were collected, grouped according to the prognosis, and statistically analyzed. RESULTS: A total of 141 patients were collected, of which 27 patients died and 114 patients were in the survival group. Through statistical analysis, patients with combined hemorrhagic manifestations, disturbance of consciousness, lymphopenia, elevated lipase, and prolonged thrombin time on admission were independent risk factors for patients' death. By plotting the working characteristic curve of the subjects, as well as calculating the area under the curve, the results showed that the AUC of lymphopenia count was 0.670, 95% CI (0.563-0.776), P = 0.006; the AUC of elevated serum lipase index was 0.789, 95% CI (0.699-0.878), p < 0.001; the AUC of prolonged thrombin time was 0.749, 95% CI (0.645-0.854), p < 0.001. CONCLUSION: Patients with hemorrhagic manifestations, disturbance of consciousness, lymphocyte reduction, elevated serum lipase, and prolonged thrombin time on admission are more worthy of the clinician's attention, and require early and effective interventions to avoid further disease progression.


Subject(s)
Severe Fever with Thrombocytopenia Syndrome , Humans , Male , Female , Severe Fever with Thrombocytopenia Syndrome/mortality , Severe Fever with Thrombocytopenia Syndrome/blood , Severe Fever with Thrombocytopenia Syndrome/virology , Retrospective Studies , Middle Aged , Cross-Sectional Studies , Aged , Prognosis , Risk Factors , Phlebovirus , Adult , Aged, 80 and over
5.
Medicine (Baltimore) ; 103(32): e39268, 2024 Aug 09.
Article in English | MEDLINE | ID: mdl-39121308

ABSTRACT

RATIONALE: The geographic spread of Japanese spotted fever (JSF) in China is gradually expanding, particularly in regions where severe fever with thrombocytopenia syndrome (SFTS) is highly prevalent, with both diseases sharing similarities in epidemiology and clinical presentation. The microbiological diagnosis of JSF is challenging, compounded by low awareness among healthcare professionals in newly affected areas. Moreover, primary healthcare facilities without polymerase chain reaction (PCR) testing capabilities for SFTS often misdiagnose JSF as SFTS. PATIENT CONCERNS: All 3 patients had a history of working in the fields, with cold like symptoms in the early fever stages, but the fever did not improve after a few days. The accompanying symptoms were also very different. Physical examination revealed enlarged lymph nodes, different forms of rash, with or without eschar. Laboratory tests showed thrombocytopenia, eosinophilia, elevated lactate dehydrogenase, and transaminase, with 1 patient experiencing renal damage. It is worth noting that these 3 patients reside in an area where SFTS is endemic, and there have been no prior reports of JSF. They exhibited clinical symptoms and laboratory test results closely resembling those of SFTS. Therefore, they were initially misdiagnosed with SFTS in their local hospitals. DIAGNOSES: The 3 patients who arrived at our hospital 7 days after symptom onset and were subsequently diagnosed with JSF by metagenomic next-generation sequencing (mNGS). INTERVENTIONS: Doxycycline treatment for 1 week. OUTCOMES: The patients' symptoms quickly improved with no side effects, and the results of laboratory tests went back to normal. LESSONS: By comparing the clinical characteristics of JSF patients and SFTS patients comprehensively, we found that APTT and procalcitonin levels may be valuable in assisting in the identification of SFTS and JSF. In all areas where tick-borne diseases are endemic, include SFTS-epidemic areas, we recommend using the Weil-Felix test to screen for potential rickettsiosis in patients presenting with fever and thrombocytopenia with or without rash in primary healthcare settings, as well as simultaneous testing for the SFTS virus and spotted fever group rickettsioses sequence. Additionally, mNGS sequencing should be used to confirm the diagnosis and provide information for epidemiological investigations in patients who are suspected of having spotted fever group rickettsiosis.


Subject(s)
Phlebovirus , Humans , Male , Phlebovirus/isolation & purification , Middle Aged , Severe Fever with Thrombocytopenia Syndrome/diagnosis , Severe Fever with Thrombocytopenia Syndrome/epidemiology , China/epidemiology , Spotted Fever Group Rickettsiosis/diagnosis , Spotted Fever Group Rickettsiosis/epidemiology , Female , Adult , Doxycycline/therapeutic use , Endemic Diseases , Diagnostic Errors , Anti-Bacterial Agents/therapeutic use
6.
J Med Virol ; 96(8): e29854, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39135475

ABSTRACT

Severe fever with thrombocytopenia syndrome (SFTS) has a high mortality rate compared to other infectious diseases. SFTS is particularly associated with a high risk of mortality in immunocompromised individuals, while most patients who die of SFTS exhibit symptoms of severe encephalitis before death. However, the region of brain damage and mechanisms by which the SFTS virus (SFTSV) causes encephalitis remains unknown. Here, we revealed that SFTSV infects the brainstem and spinal cord, which are regions of the brain associated with respiratory function, and motor nerves in IFNAR1-/- mice. Further, we show that A1-reactive astrocytes are activated, causing nerve cell death, in infected mice. Primary astrocytes of SFTSV-infected IFNAR1-/- mice also induced neuronal cell death through the activation of A1-reactive astrocytes. Herein, we showed that SFTSV induces fatal neuroinflammation in the brain regions important for respiratory function and motor nerve, which may underlie mortality in SFTS patients. This study provides new insights for the treatment of SFTS, for which there is currently no therapeutic approach.


Subject(s)
Astrocytes , Bunyaviridae Infections , Mice, Knockout , Phlebovirus , Receptor, Interferon alpha-beta , Animals , Astrocytes/virology , Astrocytes/pathology , Mice , Receptor, Interferon alpha-beta/genetics , Receptor, Interferon alpha-beta/deficiency , Phlebovirus/genetics , Phlebovirus/physiology , Phlebovirus/pathogenicity , Bunyaviridae Infections/virology , Bunyaviridae Infections/pathology , Bunyaviridae Infections/immunology , Brain/virology , Brain/pathology , Brain/immunology , Spinal Cord/virology , Spinal Cord/pathology , Disease Models, Animal , Neurons/virology , Neurons/pathology , Mice, Inbred C57BL , Brain Stem/virology , Brain Stem/pathology , Cell Death
7.
Viruses ; 16(8)2024 Aug 20.
Article in English | MEDLINE | ID: mdl-39205306

ABSTRACT

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.


Subject(s)
Antiviral Agents , Phlebovirus , Selective Estrogen Receptor Modulators , Severe Fever with Thrombocytopenia Syndrome , Virus Replication , Animals , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Phlebovirus/drug effects , Mice , Selective Estrogen Receptor Modulators/pharmacology , Selective Estrogen Receptor Modulators/therapeutic use , Severe Fever with Thrombocytopenia Syndrome/drug therapy , Severe Fever with Thrombocytopenia Syndrome/virology , Virus Replication/drug effects , Humans , Chlorocebus aethiops , Female , Cell Line , Vero Cells , Disease Models, Animal
8.
PLoS Negl Trop Dis ; 18(8): e0012411, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39207951

ABSTRACT

Severe fever with thrombocytopenia syndrome (SFTS) is a newly identified tick-borne viral hemorrhagic fever caused by Dabie Banda virus (DBV). The virus was first discovered in eastern China in 2009 and is now considered an infectious disease with a mortality rate ranging from 6.3% to 30%. The best strategy for controlling SFTS is to develop effective vaccines. However, no approved vaccines are currently available to prevent this disease, despite the number of extensive and in-depth studies conducted on DBV in the past few years. This review focuses on the structure of DBV and the induced host immune responses which are the fundamental factors in vaccine development, and thoroughly summarizes the current research progress on DBV vaccines. The developing DBV vaccines include protein subunit vaccines, live attenuated vaccines, recombinant virus vector vaccines, and DNA vaccines. At present, almost all candidate vaccines for DBV are in the laboratory development or preclinical stages. There remain challenges in successfully developing clinically approved DBV vaccines.


Subject(s)
Viral Vaccines , Humans , Viral Vaccines/immunology , Animals , Vaccines, Attenuated/immunology , Vaccine Development , Severe Fever with Thrombocytopenia Syndrome/prevention & control , Severe Fever with Thrombocytopenia Syndrome/immunology , Phlebovirus/immunology , Phlebovirus/genetics , Vaccines, DNA/immunology , Vaccines, Subunit/immunology
9.
Front Cell Infect Microbiol ; 14: 1419015, 2024.
Article in English | MEDLINE | ID: mdl-39165922

ABSTRACT

Introduction: Severe fever with thrombocytopenia syndrome (SFTS) is prevalent in East Asia. However, the use of glucocorticoids (GCs) in the treatment of SFTS remains controversial. Methods: In this retrospective cohort study, we collected the data from patients with SFTS at Wuhan Union Hospital to evaluate the effect of GC therapy. Mortality and secondary infections were compared as outcomes. After searching public databases, we also included articles that examined GC use in patients with SFTS for meta-analysis. Results: Patients treated with GC had higher fatality rates (21.1% vs. 11.9%, respectively; P=0.006) and a longer length of stay (10.6 ± 5.1 vs. 9.5 ± 4.2, respectively; P=0.033). In cohorts adjusted using propensity score matching and inverse probability of treatment weighting, no significant differences in fatality rates and length of stay were observed. A meta-analysis of 4243 SFTS patient revealed that those treated with GCs had significantly higher mortality (OR=3.46, 95% CI =2.12-5.64, P<0.00001) and secondary infection rate (OR=1.97, 95% CI=1.45-2.67, P<0.0001). Discussion: GC should be used cautiously when treating SFTS. No significant differences were identified in terms of mortality and secondary infection rates between patients with SFTS treated with or without GC.


Subject(s)
Glucocorticoids , Severe Fever with Thrombocytopenia Syndrome , Humans , Retrospective Studies , Severe Fever with Thrombocytopenia Syndrome/drug therapy , Severe Fever with Thrombocytopenia Syndrome/mortality , Glucocorticoids/therapeutic use , Male , Middle Aged , Female , Aged , Phlebovirus/drug effects , Treatment Outcome , Length of Stay , Adult , China/epidemiology
10.
Mol Biol Evol ; 41(8)2024 Aug 02.
Article in English | MEDLINE | ID: mdl-39191515

ABSTRACT

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a tick-borne virus recognized by the World Health Organization as an emerging infectious disease of growing concern. Utilizing phylodynamic and phylogeographic methods, we have reconstructed the origin and transmission patterns of SFTSV lineages and the roles demographic, ecological, and climatic factors have played in shaping its emergence and spread throughout Asia. Environmental changes and fluctuations in tick populations, exacerbated by the widespread use of pesticides, have contributed significantly to its geographic expansion. The increased adaptability of Lineage L2 strains to the Haemaphysalis longicornis vector has facilitated the dispersal of SFTSV through Southeast Asia. Increased surveillance and proactive measures are needed to prevent further spread to Australia, Indonesia, and North America.


Subject(s)
Phlebovirus , Phylogeography , Severe Fever with Thrombocytopenia Syndrome , Phlebovirus/genetics , Animals , Asia, Southeastern , Severe Fever with Thrombocytopenia Syndrome/virology , Severe Fever with Thrombocytopenia Syndrome/transmission , Humans , Phylogeny , Arachnid Vectors/virology , Ticks/virology , Ixodidae/virology , Introduced Species
11.
Virulence ; 15(1): 2384563, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39072499

ABSTRACT

Phenuiviruses are a class of segmented negative-sense single-stranded RNA viruses, typically consisting of three RNA segments that encode four distinct proteins. The emergence of pathogenic phenuivirus strains, such as Rift Valley fever phlebovirus (RVFV) in sub-Saharan Africa, Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) in East and Southeast Asia, and Heartland Virus (HRTV) in the United States has presented considerable challenges to global public health in recent years. The innate immune system plays a crucial role as the initial defense mechanism of the host against invading pathogens. In addition to continued research aimed at elucidating the epidemiological characteristics of phenuivirus, significant advancements have been made in investigating its viral virulence factors (glycoprotein, non-structural protein, and nucleoprotein) and potential host-pathogen interactions. Specifically, efforts have focused on understanding mechanisms of viral immune evasion, viral assembly and egress, and host immune networks involving immune cells, programmed cell death, inflammation, nucleic acid receptors, etc. Furthermore, a plethora of technological advancements, including metagenomics, metabolomics, single-cell transcriptomics, proteomics, gene editing, monoclonal antibodies, and vaccines, have been utilized to further our understanding of phenuivirus pathogenesis and host immune responses. Hence, this review aims to provide a comprehensive overview of the current understanding of the mechanisms of host recognition, viral immune evasion, and potential therapeutic approaches during human pathogenic phenuivirus infections focusing particularly on RVFV and SFTSV.


Subject(s)
Host-Pathogen Interactions , Immunity, Innate , Humans , Host-Pathogen Interactions/immunology , Phlebovirus/immunology , Phlebovirus/genetics , Phlebovirus/pathogenicity , Immune Evasion , Virulence Factors/genetics , Virulence Factors/immunology , Rift Valley fever virus/immunology , Rift Valley fever virus/genetics , Rift Valley fever virus/pathogenicity , Immune System/virology , Immune System/immunology
12.
PLoS Negl Trop Dis ; 18(7): e0012024, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39012922

ABSTRACT

Central China has been reported to be one of the most important endemic areas of zoonotic infection by spotted fever group rickettsiae (SFGR), severe fever with thrombocytopenia syndrome virus (SFTSV) and hantaan virus (HTNV). Due to similar clinical symptoms, it is challenging to make a definite diagnosis rapidly and accurately in the absence of microbiological tests. In the present study, an all-in-one real-time PCR assay was developed for the simultaneous detection of nucleic acids from SFGR, SFTSV and HTNV. Three linear standard curves for determining SFGR-ompA, SFTSV-L and HTNV-L were obtained within the range of 101-106 copies/µL, with the PCR amplification efficiencies ranging from 93.46% to 96.88% and the regression coefficients R2 of >0.99. The detection limit was 1.108 copies/µL for SFGR-ompA, 1.075 copies/µL for SFTSV-L and 1.006 copies/µL for HTNV-L, respectively. Both the within-run and within-laboratory coefficients of variation on the cycle threshold (Ct) values were within the range of 0.53%-2.15%. It was also found there was no statistical difference in the Ct values between single template and multiple templates (PSFGR-ompA = 0.186, PSFTSV-L = 0.612, PHTNV-L = 0.298). The sensitivity, specificity, positive and negative predictive value were all 100% for determining SFGR-ompA and SFTSV-L, 97%, 100%, 100% and 99.6% for HTNV-L, respectively. Therefore, the all-in-one real-time PCR assay appears to be a reliable, sensitive, rapid, high-throughput and low cost-effective method to diagnose the zoonotic infection by SFGR, SFTSV and HTNV.


Subject(s)
Hantaan virus , Phlebovirus , Real-Time Polymerase Chain Reaction , Sensitivity and Specificity , Severe Fever with Thrombocytopenia Syndrome , China/epidemiology , Hantaan virus/genetics , Hantaan virus/isolation & purification , Real-Time Polymerase Chain Reaction/methods , Phlebovirus/genetics , Phlebovirus/isolation & purification , Humans , Severe Fever with Thrombocytopenia Syndrome/diagnosis , Rickettsia/isolation & purification , Rickettsia/genetics , Spotted Fever Group Rickettsiosis/diagnosis , Animals
13.
Methods Mol Biol ; 2824: 259-280, 2024.
Article in English | MEDLINE | ID: mdl-39039418

ABSTRACT

In negative strand RNA viruses, ribonucleoproteins, not naked RNA, constitute the template used by the large protein endowed with polymerase activity for replicating and transcribing the viral genome. Here we give an overview of the structures and functions of the ribonucleoprotein from phleboviruses. The nucleocapsid monomer, which constitutes the basic structural unit, possesses a flexible arm allowing for a conformational switch between a closed monomeric state and the formation of a polymeric filamentous structure competent for viral RNA binding and encapsidation in the open state of N. The modes of N-N oligomerization as well as interactions with vRNA are described. Finally, recent advances in tomography open exciting perspectives for a more complete understanding of N-L interactions and the design of specific antiviral compounds.


Subject(s)
Phlebovirus , RNA, Viral , Ribonucleoproteins , Ribonucleoproteins/metabolism , Ribonucleoproteins/chemistry , RNA, Viral/metabolism , RNA, Viral/genetics , Phlebovirus/metabolism , Phlebovirus/genetics , Humans , Models, Molecular , Nucleocapsid/metabolism , Nucleocapsid/chemistry , Protein Multimerization , Protein Conformation , Genome, Viral
14.
Metabolomics ; 20(4): 84, 2024 Jul 27.
Article in English | MEDLINE | ID: mdl-39066899

ABSTRACT

INTRODUCTION: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by the SFTS virus (SFTSV), which has a wide geographic distribution. The primary clinical manifestations of SFTS are fever and thrombocytopenia, with multiorgan failure being the leading cause of death. While most patients recover with treatment, little is known about the potential long-term metabolic effects of SFTSV infection. OBJECTIVES: This study aimed to shed light on dysregulated metabolic pathways and cytokine responses following SFTSV infection, which pose significant risks to the short-term and long-term health of affected individuals. METHODS: Fourteen laboratory-confirmed clinical SFTS cases and thirty-eight healthy controls including 18 SFTSV IgG-positive and 20 IgG-negative individuals were recruited from Taizhou city of Zhejiang province, Eastern China. Inclusion criteria of healthy controls included residing in the study area for at least one year, absence of fever or other symptoms in the past two weeks, and no history of SFTS diagnosis. Ultrahigh-performance liquid chromatography-mass spectrometry (UHPLC-MS) was used to obtain the relative abundance of plasma metabolites. Short-term metabolites refer to transient alterations present only during SFTSV infection, while long-term metabolites persistently deviate from normal levels even after recovery from SFTSV infection. Additionally, the concentrations of 12 cytokines were quantified through fluorescence intensity measurements. Differential metabolites were screened using orthogonal projections to latent structures discriminant analysis (OPLS-DA) and the Wilcoxon rank test. Metabolic pathway analysis was performed using MetaboAnalyst. Between-group differences of metabolites and cytokines were examined using the Wilcoxon rank test. Correlation matrices between identified metabolites and cytokines were analyzed using Spearman's method. RESULTS AND CONCLUSIONS: We screened 122 long-term metabolites and 108 short-term metabolites by analytical comparisons and analyzed their correlations with 12 cytokines. Glycerophospholipid metabolism (GPL) was identified as a significant short-term metabolic pathway suggesting that the activation of GPL might be linked to the self-replication of SFTSV, whereas pentose phosphate pathway and alanine, aspartate, and glutamate metabolism were indicated as significant long-term metabolic pathways playing a role in combating long-standing oxidative stress in the patients. Furthermore, our study suggests a new perspective that α-ketoglutarate could serve as a dietary supplement to protect recovering SFTS patients.


Subject(s)
Cytokines , Phlebovirus , Severe Fever with Thrombocytopenia Syndrome , Humans , Severe Fever with Thrombocytopenia Syndrome/metabolism , Severe Fever with Thrombocytopenia Syndrome/virology , Cytokines/metabolism , Cytokines/blood , Middle Aged , Male , Female , Phlebovirus/metabolism , Aged , Adult , Chromatography, High Pressure Liquid , Metabolomics/methods , Case-Control Studies , Metabolic Networks and Pathways , Mass Spectrometry/methods , China
15.
PLoS Pathog ; 20(7): e1012348, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39008518

ABSTRACT

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.


Subject(s)
Glycoproteins , Phlebovirus , Viral Tropism , Animals , Glycosylation , Mice , Virulence , Phlebovirus/pathogenicity , Phlebovirus/genetics , Glycoproteins/metabolism , Glycoproteins/genetics , Humans , Severe Fever with Thrombocytopenia Syndrome/virology , Mice, Inbred C57BL , Bunyaviridae Infections/virology , Bunyaviridae Infections/metabolism , Ticks/virology , Mice, Knockout , Orthobunyavirus/pathogenicity , Orthobunyavirus/genetics , Orthobunyavirus/metabolism
16.
PLoS Negl Trop Dis ; 18(7): e0012306, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38976750

ABSTRACT

BACKGROUND: Rodents are recognized as major reservoirs of numerous zoonotic pathogens and are involved in the transmission and maintenance of infectious diseases. Furthermore, despite their importance, diseases transmitted by rodents have been neglected. To date, there have been limited epidemiological studies on rodents, and information regarding their involvement in infectious diseases in the Republic of Korea (ROK) is still scarce. METHODOLOGY/PRINCIPAL FINDINGS: We investigated rodent-borne pathogens using nested PCR/RT-PCR from 156 rodents including 151 Apodemus agrarius and 5 Rattus norvegicus from 27 regions in eight provinces across the ROK between March 2019 and November 2020. Spleen, kidney, and blood samples were used to detect Anaplasma phagocytophilum, Bartonella spp., Borrelia burgdorferi sensu lato group, Coxiella burnetii, Leptospira interrogans, and severe fever with thrombocytopenia syndrome virus (SFTSV). Of the 156 rodents, 73 (46.8%) were infected with Bartonella spp., 25 (16.0%) with C. burnetii, 24 (15.4%) with L. interrogans, 21 (13.5%) with A. phagocytophilum, 9 (5.8%) with SFTSV, and 5 (3.2%) with Borrelia afzelii. Co-infections with two and three pathogens were detected in 33 (21.1%) and 11 rodents (7.1%), respectively. A. phagocytophilum was detected in all regions, showing a widespread occurrence in the ROK. The infection rates of Bartonella spp. were 83.3% for B. grahamii and 16.7% for B. taylorii. CONCLUSIONS/SIGNIFICANCE: To the best of our knowledge, this is the first report of C. burnetii and SFTSV infections in rodents in the ROK. This study also provides the first description of various rodent-borne pathogens through an extensive epidemiological survey in the ROK. These results suggest that rodents harbor various pathogens that pose a potential threat to public health in the ROK. Our findings provide useful information on the occurrence and distribution of zoonotic pathogens disseminated among rodents and emphasize the urgent need for rapid diagnosis, prevention, and control strategies for these zoonotic diseases.


Subject(s)
Anaplasma phagocytophilum , Bartonella , Coxiella burnetii , Zoonoses , Animals , Republic of Korea/epidemiology , Zoonoses/epidemiology , Zoonoses/microbiology , Rats , Coxiella burnetii/isolation & purification , Coxiella burnetii/genetics , Bartonella/isolation & purification , Bartonella/genetics , Anaplasma phagocytophilum/isolation & purification , Anaplasma phagocytophilum/genetics , Rodentia/microbiology , Murinae/microbiology , Animals, Wild/microbiology , Animals, Wild/virology , Rodent Diseases/epidemiology , Rodent Diseases/microbiology , Rodent Diseases/virology , Phlebovirus/genetics , Phlebovirus/isolation & purification , Disease Reservoirs/microbiology , Leptospira interrogans/isolation & purification , Leptospira interrogans/genetics
17.
Am J Trop Med Hyg ; 111(3): 661-670, 2024 Sep 04.
Article in English | MEDLINE | ID: mdl-38981464

ABSTRACT

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infection with a high case fatality rate. The serious clinical features need to be further defined. We performed a retrospective analysis among SFTS patients in South Korea during 2016-2021 to update the current status. The basic epidemiology of all reported cases was analyzed, and the detailed clinical data of the subjects were further collected from study hospitals selected in terms of their geographic location and capability of SFTS care. Cases of SFTS were reported across the country and were greatly increased since the initial endemic phase, even under the passive surveillance system. The case fatality rate remained at approximately 16.8%. Coinfections at admission were present in 7.8% of the patients. Major complications included bleeding (15.2%), hemophagocytic lymphohistiocytosis (6.7%), bacteremia or candidemia (4.0%), and invasive pulmonary aspergillosis (1.7%). It took a median 4 days from the onset of illness to hospital admission. Rapid clinical deterioration was observed with a median 1 day for intensive care unit admission, 3 days for mechanical ventilation, 4 days for renal replacement therapy, and 5 days for death, all after the hospitalization. Multivariate analysis showed that the fatality was associated with older age, bacteremia, or candidemia during hospitalization, and the presence of several variables at admission such as fever, altered mentality, aspartate aminotransferase >200 IU/L, serum creatinine level >1.2 mg/dL, and prolonged prothrombin time and activated partial thromboplastin time. Treatment options to improve clinical outcomes are limited, despite best supportive care. Specific treatment is urgently needed to change the fatal course.


Subject(s)
Severe Fever with Thrombocytopenia Syndrome , Humans , Republic of Korea/epidemiology , Female , Male , Middle Aged , Aged , Retrospective Studies , Severe Fever with Thrombocytopenia Syndrome/epidemiology , Adult , Disease Progression , Aged, 80 and over , Hemorrhage/epidemiology , Hemorrhage/etiology , Phlebovirus , Bacteremia/epidemiology , Bacteremia/microbiology , Bacteremia/mortality
18.
Acta Trop ; 257: 107279, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38871069

ABSTRACT

The causative agent of severe fever with thrombocytopenia syndrome (SFTS) is Bandavirus dabieense, an emerging tick-borne zoonotic pathogen. Migratory birds have often been suggested as potential carriers of ticks that can transmit Bandavirus dabieense; however, their role remains unclear. The Republic of Korea (ROK) holds an important position as a stopover on the East Asian-Australasian Flyway. The present study aimed to investigate the potential involvement of migratory birds in the transmission of the SFTS virus (SFTSV) in the ROK. A total of 4,497 ticks were collected across various regions, including Heuksando and Daecheongdo, in the ROK, from bird migration seasons in 2022 and 2023. Genetic analysis of the SFTSV was performed for 96 ticks collected from 20 different species of migratory birds. Polymerase chain reaction (PCR) fragments of SFTSV were detected in one Haemaphysalis concinna nymph collected from a Black-faced Bunting (Emberiza spodocephala) and one Ixodes turdus nymph collected from an Olive-backed Pipit (Anthus hodgsoni) on Daecheongdo and Heuksando, respectively, during their northward migration in two spring seasons. This finding suggests that migratory birds can be considered as possible carriers and long-distance dispersers of ticks and associated tick-borne diseases. This study highlights the importance of clarifying the role and impact of migratory birds in the rapid expansion of tick-borne diseases, facilitating enhanced preparedness and the development of mitigation measures against emerging SFTS across and beyond East Asia.


Subject(s)
Animal Migration , Birds , Phlebovirus , Phylogeny , Animals , Republic of Korea , Phlebovirus/isolation & purification , Phlebovirus/genetics , Phlebovirus/classification , Birds/virology , Bird Diseases/virology , Bird Diseases/parasitology , Ixodes/virology , Ticks/virology , Ticks/classification , Severe Fever with Thrombocytopenia Syndrome/virology
19.
Am J Trop Med Hyg ; 111(2): 429-432, 2024 Aug 07.
Article in English | MEDLINE | ID: mdl-38889707

ABSTRACT

No specific treatment has been developed for severe fever with thrombocytopenia syndrome (SFTS). However, the prognosis can improve with early plasma exchange. Therefore, rapid and accurate detection of SFTS virus is important for diagnosis and prognosis. Direct real-time reverse transcription polymerase chain reaction (RT-PCR) testing is easier and more time-efficient than conventional real-time RT-PCR. Our study compared direct real-time RT-PCR efficiency without the RNA extraction and purification of conventional real-time RT-PCR. Samples were collected from 18 patients with SFTS and five without SFTS. A strong correlation (r = 0.774, 95% CI: 0.652-0.857, P <0.01) was found between conventional and direct real-time RT-PCR assays. Direct real-time RT-PCR showed 84.4% sensitivity and 92.0% specificity for viral detection. Direct real-time RT-PCR is an effective diagnostic tool for patients with acute phase SFTS, but further optimization is required for viral detection.


Subject(s)
Phlebovirus , RNA, Viral , Reverse Transcriptase Polymerase Chain Reaction , Sensitivity and Specificity , Severe Fever with Thrombocytopenia Syndrome , Humans , Severe Fever with Thrombocytopenia Syndrome/diagnosis , Severe Fever with Thrombocytopenia Syndrome/virology , Phlebovirus/genetics , Phlebovirus/isolation & purification , RNA, Viral/isolation & purification , RNA, Viral/genetics , Reverse Transcriptase Polymerase Chain Reaction/methods , Real-Time Polymerase Chain Reaction/methods , Male , Female , Middle Aged , Aged , Adult
20.
Am J Trop Med Hyg ; 111(2): 412-415, 2024 Aug 07.
Article in English | MEDLINE | ID: mdl-38917821

ABSTRACT

Phleboviruses are an emerging threat to public health. Recent surveillance efforts in Kenya have unveiled novel phleboviruses. Despite these efforts, there remain knowledge gaps. This study tested female sandflies from diverse ecological settings in Kenya for arboviruses. Sandfly pools were cultured in Vero-CCL cells. Pools showing reproducible cytopathic effects were subjected to next-generation sequencing, followed by phylogenetic analysis. In vitro, cell kinetics analysis was performed using both Vero-E6 cells and C6/36 mosquito cells. One pool from Baringo, Kenya, tested positive for Bogoria virus (BOGV). The BOGV genome clustered in a single clade with previously obtained BOGV genomes. No significant differences were observed between Vero and C6/36 cell growth kinetics. This study has confirmed the presence of BOGV among sandflies in Baringo Kenya and demonstrated growth in mosquito cells.


Subject(s)
Psychodidae , Animals , Kenya , Psychodidae/virology , Female , Vero Cells , Phylogeny , Phlebovirus/genetics , Phlebovirus/isolation & purification , Phlebovirus/classification , Chlorocebus aethiops , Insect Vectors/virology , Cell Line , Kinetics , Genome, Viral
SELECTION OF CITATIONS
SEARCH DETAIL