-
Microbes and Infection Feb 2015Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever in East Asia with case fatality up to 50%. SFTS is caused by SFTSV, a tick borne... (Review)
Review
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever in East Asia with case fatality up to 50%. SFTS is caused by SFTSV, a tick borne bunyavirus. In endemic area in China 1%-3% population was infected with SFTSV, but age is critical risk factor for hospitalization and death of SFTS patients.
Topics: Animals; Arthropod Vectors; Bunyaviridae Infections; China; Disease Models, Animal; Hemorrhagic Fevers, Viral; Humans; Phlebovirus; Syndrome; Thrombocytopenia; Virus Replication
PubMed: 25498868
DOI: 10.1016/j.micinf.2014.12.002 -
Missouri Medicine 2018We evaluated (lone star tick) and (American dog tick) in northeast Missouri for the presence of , , and bacteria and Heartland virus. We screened 436 individual adult...
We evaluated (lone star tick) and (American dog tick) in northeast Missouri for the presence of , , and bacteria and Heartland virus. We screened 436 individual adult lone star ticks (86% of all ticks collected) and infection rates were 6% for , 19% for , 3% for , 36% for and 1% for . In the 189 individual American dog ticks, infection rates were 19% for , 15% for , 4% for , and 5% for . In addition, we screened 20 pools of adults and 30 pools of nymphs for the Heartland virus which was not detected. Understanding the presence and epidemiology of these causative ( and ) and suspected () agents in Missouri should increase awareness of potential tick-borne disease in the medical community.
Topics: Adult; Animals; Borrelia; Bunyaviridae Infections; Ehrlichia; Ehrlichiosis; Female; Humans; Ixodidae; Male; Missouri; Phlebovirus; Prevalence; Rickettsia; Rickettsia Infections; Tick-Borne Diseases
PubMed: 30228710
DOI: No ID Found -
Journal of Virology Mar 2019Bunyaviruses have a tripartite negative-sense RNA genome. Due to the segmented nature of these viruses, if two closely related viruses coinfect the same host or vector...
Bunyaviruses have a tripartite negative-sense RNA genome. Due to the segmented nature of these viruses, if two closely related viruses coinfect the same host or vector cell, it is possible that RNA segments from either of the two parental viruses will be incorporated into progeny virions to give reassortant viruses. Little is known about the ability of tick-borne phleboviruses to reassort. The present study describes the development of minigenome assays for the tick-borne viruses Uukuniemi phlebovirus (UUKV) and Heartland phlebovirus (HRTV). We used these minigenome assays in conjunction with the existing minigenome system of severe fever with thrombocytopenia syndrome (SFTS) phlebovirus (SFTSV) to assess the abilities of viral N and L proteins to recognize, transcribe, and replicate the M segment-based minigenome of a heterologous virus. The highest minigenome activity was detected with the M segment-based minigenomes of cognate viruses. However, our findings indicate that several combinations utilizing N and L proteins of heterologous viruses resulted in M segment minigenome activity. This suggests that the M segment untranslated regions (UTRs) are recognized as functional promoters of transcription and replication by the N and L proteins of related viruses. Further, virus-like particle assays demonstrated that HRTV glycoproteins can package UUKV and SFTSV S and L segment-based minigenomes. Taken together, these results suggest that coinfection with these viruses could lead to the generation of viable reassortant progeny. Thus, the tools developed in this study could aid in understanding the role of genome reassortment in the evolution of these emerging pathogens in an experimental setting. In recent years, there has been a large expansion in the number of emerging tick-borne viruses that are assigned to the genus. Bunyaviruses have a tripartite segmented genome, and infection of the same host cell by two closely related bunyaviruses can, in theory, result in eight progeny viruses with different genome segment combinations. We used genome analogues expressing reporter genes to assess the abilities of nucleocapsid protein and RNA-dependent RNA polymerase to recognize the untranslated region of a genome segment of a related phlebovirus, and we used virus-like particle assays to assess whether viral glycoproteins can package genome analogues of related phleboviruses. Our results provide strong evidence that these emerging pathogens could reassort their genomes if they were to meet in nature in an infected host or vector. This reassortment process could result in viruses with new pathogenic properties.
Topics: Animals; Bunyaviridae Infections; Cell Line; Genome, Viral; Mesocricetus; Phlebovirus; Phylogeny; Promoter Regions, Genetic; Ticks; Viral Nonstructural Proteins
PubMed: 30567991
DOI: 10.1128/JVI.02068-18 -
Viruses May 2021Sandfly-borne phleboviruses (phylum , realm , kingdom , genus ) comprise three genome segments of ribonucleic acid (RNA) and which encode an RNA-dependent RNA...
Sandfly-borne phleboviruses (phylum , realm , kingdom , genus ) comprise three genome segments of ribonucleic acid (RNA) and which encode an RNA-dependent RNA polymerase, which they use to transcribe the viral RNA genome into messenger RNA and to replicate the genome. At least some of these viruses cause mild 3-day fevers in humans but some also have been associated with more severe illnesses in humans. The 67 recognized phleboviruses are listed here in a table composed by the authors from International Committee on Taxonomy of Viruses reports as well as the scientific literature.
Topics: Animals; Genome, Viral; Phlebovirus; Phylogeny; Psychodidae; Reassortant Viruses
PubMed: 34063467
DOI: 10.3390/v13050918 -
Euro Surveillance : Bulletin Europeen... Nov 2023BackgroundVarious pathogens, including bacteria, fungi, parasites, and viruses can lead to meningitis. Among viruses causing meningitis, Toscana virus (TOSV), a... (Observational Study)
Observational Study
BackgroundVarious pathogens, including bacteria, fungi, parasites, and viruses can lead to meningitis. Among viruses causing meningitis, Toscana virus (TOSV), a phlebovirus, is transmitted through sandfly bites. TOSV infection may be suspected if patients with enterovirus- and herpesvirus-negative aseptic (non-bacterial) meningitis recall recent insect bites. Other epidemiological factors (season, rural area) may be considered. The broad range of possible meningitis aetiologies poses considerable diagnosis challenges. Untargeted metagenomic next-generation sequencing (mNGS) can potentially identify pathogens, which are not considered or detected in routine diagnostic panels.AimIn this retrospective, single-centre observational study, we investigated mNGS usefulness to understand the cause of meningitis when conventional approaches fail.MethodsCerebrospinal fluid (CSF) samples from patients hospitalised in southern Spain in 2015-2019 with aseptic meningitis and no aetiology found by conventional testing, were subjected to mNGS. Patients' demographic characteristics had been recorded and physicians had asked them about recent insect bites. Obtained viral genome sequences were phylogenetically analysed.ResultsAmong 23 idiopathic cases, TOSV was identified in eight (all male; median age: 39 years, range: 15-78 years). Five cases lived in an urban setting, three occurred in autumn and only one recalled insect bites. Phylogenetic analysis of TOSV segment sequences supported one intra-genotype reassortment event.ConclusionsOur study highlights the usefulness of mNGS for identifying viral pathogens directly in CSF. In southern Spain, TOSV should be considered regardless of recalling of insect bites or other epidemiological criteria. Detection of a disease-associated reassortant TOSV emphasises the importance of monitoring the spread and evolution of phleboviruses in Mediterranean countries.
Topics: Humans; Male; Adult; Sandfly fever Naples virus; Insect Bites and Stings; Phylogeny; Retrospective Studies; Spain; Meningitis
PubMed: 37943504
DOI: 10.2807/1560-7917.ES.2023.28.45.2200913 -
Viruses Sep 2023The non-structural protein (NSs) and nucleoprotein (NP) of the severe fever with thrombocytopenia syndrome virus (SFTSV) encoded by the S segment are crucial for viral...
Non-Structural Protein-W61 as a Novel Target in Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV): An In-Vitro and In-Silico Study on Protein-Protein Interactions with Nucleoprotein and Viral Replication.
The non-structural protein (NSs) and nucleoprotein (NP) of the severe fever with thrombocytopenia syndrome virus (SFTSV) encoded by the S segment are crucial for viral pathogenesis. They reside in viroplasm-like structures (VLS), but their interaction and their significance in viral propagation remain unclear. Here, we investigated the significance of the association between NSs and NP during viral infection through in-silico and in-vitro analyses. Through in-silico analysis, three possible binding sites were predicted, at positions C6S (Cystein at 6th position to Serine), W61Y (Tryptophan 61st to Tyrosine), and S207T (Serine 207th to Threonine), three mutants of NSs were developed by site-directed mutagenesis and tested for NP interaction by co-immunoprecipitation. NSsW61Y failed to interact with the nucleoprotein, which was substantiated by the conformational changes observed in the structural analyses. Additionally, molecular docking analysis corroborated that the NSW61Y mutant protein does not interact well compared to wild-type NSs. Over-expression of wild-type NSs in HeLa cells increased the SFTSV replication by five folds, but NSsW61Y exhibited 1.9-folds less viral replication than wild-type. We demonstrated that the W61Y alteration was implicated in the reduction of NSs-NP interaction and viral replication. Thus, the present study identified a critical NSs site, which could be targeted for development of therapeutic regimens against SFTSV.
Topics: Humans; Severe Fever with Thrombocytopenia Syndrome; Nucleoproteins; HeLa Cells; Signal Transduction; Molecular Docking Simulation; Bunyaviridae Infections; Phlebovirus; Virus Replication; Serine; Viral Nonstructural Proteins
PubMed: 37766369
DOI: 10.3390/v15091963 -
Uirusu 2018Seven years have passed since the discovery of a novel infectious disease, severe fever with thrombocytopenia syndrome (SFTS) caused by a novel Phlebovirus, SFTS virus... (Review)
Review
Seven years have passed since the discovery of a novel infectious disease, severe fever with thrombocytopenia syndrome (SFTS) caused by a novel Phlebovirus, SFTS virus (SFTSV), in PR China. It was also confirmed that SFTS was endemic to Japan through an identification of a woman, who died of SFTSV infection in Yamaguchi prefecture in late 2012. Approximately 6 years have passed since the discovery of SFTS-endemicity in Japan. At present, SFTS is endemic to PR China, South Korea and western Japan. SFTSV is maintained between several species of ticks such as Haemaphysalis longicornis and wild and domestic animals in nature. Therefore, we cannot escape from the risk of being infected with SFTSV. Based on the similarity in the characteristics of the clinical symptoms including the high case fatality rate, mode of infection to humans, pathology and virology between SFTS and Crimean-Congo hemorrhagic fever (CCHF), SFTS should be classified as viral hemorrhagic fever. Although the time from the discovery of SFTS is still short, there have been many scientific reports on the epidemiological, clinical, and/or pathological, and virological studies on SFTS. Favipiravir was reported to show an efficacy in the prevention and treatment of SFTSV infections in an animal model. A clinical study to evaluate the efficacy of favipiravir in the treatment of SFTS patients has been initiated in Japan. Specific and effective treatment with antiviral drugs for and preventive measures of SFTS with vaccination shoued be developed through scientific, clinical, and basic research.
Topics: Animals; Antiviral Agents; Disease Outbreaks; Asia, Eastern; Humans; Phlebotomus Fever; Phlebovirus; Ticks; Viral Vaccines
PubMed: 31105134
DOI: 10.2222/jsv.68.41 -
PLoS Pathogens Nov 2021Nuclear scaffold attachment factor A (SAFA) is a novel RNA sensor involved in sensing viral RNA in the nucleus and mediating antiviral immunity. Severe fever with...
Nuclear scaffold attachment factor A (SAFA) is a novel RNA sensor involved in sensing viral RNA in the nucleus and mediating antiviral immunity. Severe fever with thrombocytopenia syndrome virus (SFTSV) is a bunyavirus that causes SFTS with a high fatality rate of up to 30%. It remains elusive whether and how cytoplasmic SFTSV can be sensed by the RNA sensor SAFA. Here, we demonstrated that SAFA was able to detect SFTSV infection and mediate antiviral interferon and inflammatory responses. Transcription and expression levels of SAFA were strikingly upregulated under SFTSV infection. SAFA was retained in the cytoplasm by interaction with SFTSV nucleocapsid protein (NP). Importantly, SFTSV genomic RNA was recognized by cytoplasmic SAFA, which recruited and promoted activation of the STING-TBK1 signaling axis against SFTSV infection. Of note, the nuclear localization signal (NLS) domain of SAFA was important for interaction with SFTSV NP and recognition of SFTSV RNA in the cytoplasm. In conclusion, our study reveals a novel antiviral mechanism in which SAFA functions as a novel cytoplasmic RNA sensor that directly recognizes RNA virus SFTSV and mediates an antiviral response.
Topics: Antiviral Agents; Bunyaviridae Infections; Cytoplasm; HEK293 Cells; Host-Pathogen Interactions; Humans; Immunity, Innate; Nuclear Matrix-Associated Proteins; Phlebovirus
PubMed: 34788350
DOI: 10.1371/journal.ppat.1010070 -
Viruses Oct 2023Fermo virus is a that is increasingly reported in sand flies from northern Italy. The natural cycle is not fully understood, but the virus has been detected by direct...
Fermo virus is a that is increasingly reported in sand flies from northern Italy. The natural cycle is not fully understood, but the virus has been detected by direct methods only in sand flies. Although there is serological evidence that it can infect vertebrates, the virus has not been directly detected in animals or humans. Here, we have developed and reported a specific real-time PCR for Fermo virus. The availability of the described method will be useful to characterize the epidemiology of the FERV, ensuring, compared to previously available protocols, a more sensitive detection in insects and the possible detection in vertebrates to evaluate the presence of reservoirs and the pathogenic potential of the virus in humans or animals.
Topics: Animals; Humans; Phlebovirus; Real-Time Polymerase Chain Reaction; Psychodidae; Italy
PubMed: 37896859
DOI: 10.3390/v15102082 -
PLoS Neglected Tropical Diseases Dec 2022Severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV) is an emerging tick-borne phlebovirus with a high fatality rate. Previous studies have demonstrated the...
BACKGROUND
Severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV) is an emerging tick-borne phlebovirus with a high fatality rate. Previous studies have demonstrated the poor prognostic role of eosinophils (EOS) and basophils (BAS) in predicting multiple viral infections. This study aimed to explore the role of EOS and BAS in predicting prognosis of patients with SFTS.
METHODOLOGY
A total of 194 patients with SFTS who were admitted to Yantai City Hospital from November 2019 to November 2021 were included. Patients' demographic and clinical data were collected. According to the clinical prognosis, they were divided into survival and non-survival groups. Independent risk factors were determined by univariate and multivariate logistic regression analyses.
FINDINGS
There were 171 (88.14%) patients in the survived group and 23 (11.86%) patients in the non-survived group. Patients' mean age was 62.39 ± 11.85 years old, and the proportion of males was 52.1%. Older age, neurological manifestations, hemorrhage, chemosis, and increased levels of laboratory variables, such as EOS% and BAS% on admission, were found in the non-survival group compared with the survival group. EOS%, BAS%, aspartate aminotransferase (AST), direct bilirubin (DBIL), and older age on admission were noted as independent risk factors for poor prognosis of SFTS patients. The combination of the EOS% and BAS% had an area under the curve (AUC) of (0.82; 95% CI: 0.725, 0.932, P = 0.000), which showed an excellent performance in predicting prognosis of patients with SFTS compared with neutrophil-to-lymphocyte ratio (NLR), and both exhibited a satisfactory performance in predicting poor prognosis compared with De-Ritis ratio (AST/alanine aminotransferase (ALT) ratio). EOS% and BAS% were positively correlated with various biomarkers of tissue damage and the incidence of neurological complications in SFTS patients.
CONCLUSION
EOS% and BAS% are effective predictors of poor prognosis of patients with early-stage SFTS. The combination of EOS% and BAS% was found as the most effective approach.
Topics: Male; Humans; Middle Aged; Aged; Severe Fever with Thrombocytopenia Syndrome; Eosinophils; Basophils; Phlebovirus; Prognosis; Risk Factors; Bunyaviridae Infections
PubMed: 36542604
DOI: 10.1371/journal.pntd.0010967