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Ticks and Tick-borne Diseases Jul 2016Since 2009, when severe fever with thrombocytopenia syndrome virus and Heartland virus have been identified and associated with disease in humans, the interest on...
Since 2009, when severe fever with thrombocytopenia syndrome virus and Heartland virus have been identified and associated with disease in humans, the interest on tick-borne phleboviruses is increasing rapidly. The aim of the present study was to investigate the presence of tick-borne phleboviruses in Greece and compare them with respective ones detected worldwide. Ticks collected from goats and sheep in 60 sites of 13 regional units of Greece were grouped in pools (1-3 ticks per pool) and tested for the presence of phleboviral RNA. Six of 210 pools were positive; they consisted of Rhipicephalus sanguineus ticks collected from sheep in 3 regional units of Greece: Pella (2/30, 6.7%), Imathia (2/21, 9.5%), and Ioannina (2/28, 7.1%). The overall tick minimum infection rate was 2.1%. The sequences of the Greek phlebovirus (provisionally named Antigone virus) form a distinct clade in the tick-borne phleboviruses, differing by >40% from the currently known phleboviruses. Any probable implication of these viruses to public health remains to be elucidated.
Topics: Animals; Ectoparasitic Infestations; Goat Diseases; Goats; Greece; Phlebovirus; Phylogeny; RNA, Viral; Sequence Analysis, DNA; Sequence Homology; Sheep; Sheep Diseases; Ticks
PubMed: 26935112
DOI: 10.1016/j.ttbdis.2016.02.017 -
Emerging Infectious Diseases Dec 2016Heartland virus (HRTV) is a recently described phlebovirus initially isolated in 2009 from 2 humans who had leukopenia and thrombocytopenia. Serologic assessment of...
Heartland virus (HRTV) is a recently described phlebovirus initially isolated in 2009 from 2 humans who had leukopenia and thrombocytopenia. Serologic assessment of domestic and wild animal populations near the residence of 1 of these persons showed high exposure rates to raccoons, white-tailed deer, and horses. To our knowledge, no laboratory-based assessments of viremic potential of animals infected with HRTV have been performed. We experimentally inoculated several vertebrates (raccoons, goats, chickens, rabbits, hamsters, C57BL/6 mice, and interferon-α/β/γ receptor-deficient [Ag129]) mice with this virus. All animals showed immune responses against HRTV after primary or secondary exposure. However, neutralizing antibody responses were limited. Only Ag129 mice showed detectable viremia and associated illness and death, which were dose dependent. Ag129 mice also showed development of mean peak viral antibody titers >8 log PFU/mL, hemorrhagic hepatic lesions, splenomegaly, and large amounts of HRTV antigen in mononuclear cells and hematopoietic cells in the spleen.
Topics: Animal Diseases; Animals; Antibodies, Neutralizing; Antibodies, Viral; Biopsy; Bunyaviridae Infections; Cricetinae; Disease Models, Animal; Disease Susceptibility; Female; Host-Pathogen Interactions; Male; Mice; Mice, Knockout; Mortality; Phlebovirus; Rabbits; Raccoons; Receptors, Interferon; Serologic Tests; Vertebrates; Viremia
PubMed: 27869591
DOI: 10.3201/eid2212.160472 -
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 -
Annals of Emergency Medicine Sep 2014
Topics: Animals; Bunyaviridae Infections; Humans; Ixodidae; Male; Phlebovirus
PubMed: 25149964
DOI: 10.1016/j.annemergmed.2014.06.012 -
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 -
Archives of Virology Feb 2024Severe fever with thrombocytopenia syndrome (SFTS) is a hemorrhagic fever caused by SFTS virus (SFTSV), which is primarily found in East Asian countries. Despite its...
Severe fever with thrombocytopenia syndrome (SFTS) is a hemorrhagic fever caused by SFTS virus (SFTSV), which is primarily found in East Asian countries. Despite its high mortality rate and increasing incidence, no vaccines or therapeutics have yet been approved for use against SFTS. Antibody drugs have shown promise in treating lethal infectious diseases that currently have no established treatments. In the case of SFTS, however, only a limited amount of research has been done on SFTSV-neutralizing antibodies targeting the transmembrane proteins Gn and Gc, which play critical roles in viral infection. This study focuses on the production and characterization of antibodies targeting the SFTSV Gc protein. Monoclonal antibodies against Gc were generated through immunization of mice, and their antiviral activity was evaluated. Three out of four anti-Gc antibody clones from this study demonstrated dose-dependent SFTSV neutralization activity, two of which exhibited a synergistic effect on the neutralization activity of the anti-Gn antibody clone Mab4-5. Further studies are necessary to identify key sites on the SFTSV glycoprotein and to develop novel agents as well as antibodies with diverse mechanisms of action against SFTSV.
Topics: Animals; Mice; Severe Fever with Thrombocytopenia Syndrome; Glycoproteins; Phlebovirus; Hemorrhagic Fevers, Viral; Bunyaviridae Infections
PubMed: 38308735
DOI: 10.1007/s00705-024-05968-x -
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 -
The Journal of General Virology Jun 2019The genus Phlebovirus (order Bunyavirales, family Phenuiviridae) comprises 57 viruses that are grouped into nine species-complexes. Sandfly-transmitted phleboviruses are...
The genus Phlebovirus (order Bunyavirales, family Phenuiviridae) comprises 57 viruses that are grouped into nine species-complexes. Sandfly-transmitted phleboviruses are found in Europe, Africa and the Americas and are responsible for febrile illness and infections of the nervous system in humans. The aim of this study was to assess the genetic diversity of sandfly-transmitted phleboviruses in connected and isolated forest habitats throughout the Panama Canal area in Central Panama. In total, we collected 13 807 sandflies comprising eight phlebotomine species. We detected several strains pertaining to five previously unknown viruses showing maximum pairwise identities of 45-78 % to the RNA-dependent RNA polymerase genes of phleboviruses. Entire coding regions were directly sequenced from infected sandflies as virus isolation in cell culture was not successful. The viruses were tentatively named La Gloria virus (LAGV), Mona Grita virus (MOGV), Peña Blanca virus (PEBV), Tico virus (TICV) and Tres Almendras virus (TRAV). Inferred phylogenies and p-distance-based analyses revealed that PEBV groups with the Bujaru phlebovirus species-complex, TRAV with the Candiru phlebovirus species-complex and MOGV belongs to the proposed Icoarci phlebovirus species-complex, whereas LAGV and TICV seem to be distant members of the Bujaru phlebovirus species-complex. No specific vector or habitat association was found for any of the five viruses. Relative abundance of sandflies was similar over habitat types. Our study shows that blood-feeding insects originating from remote and biodiverse habitats harbour multiple previously unknown phleboviruses. These viruses should be included in future surveillance studies to assess their geographic distribution and to elucidate if these viruses cause symptoms of disease in animals or humans.
Topics: Africa; Animals; Europe; Genome, Viral; Humans; Insect Vectors; Panama; Phlebotomus Fever; Phlebovirus; Phylogeny; Psychodidae
PubMed: 31050631
DOI: 10.1099/jgv.0.001260