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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 -
Archives of Virology Mar 2021Tick-borne pathogens are an emerging public health threat worldwide. However, information on tick-borne viruses is scanty in sub-Saharan Africa. Here, by RT-PCR, 363...
Tick-borne pathogens are an emerging public health threat worldwide. However, information on tick-borne viruses is scanty in sub-Saharan Africa. Here, by RT-PCR, 363 ticks (Amblyomma, Hyalomma and Rhipicephalus) in the Namwala and Livingstone districts of Zambia were screened for tick-borne phleboviruses (TBPVs). TBPVs (L gene) were detected in 19 (5.2%) Rhipicephalus ticks in Namwala. All the detected TBPVs were Shibuyunji viruses. Phylogenetically, they were closely related to American dog tick phlebovirus. This study highlights the possible role of Rhipicephalus ticks as the main host of Shibuyunji virus and suggests that these viruses may be present outside the area where they were initially discovered.
Topics: Amblyomma; Animals; Genetic Variation; Phlebotomus Fever; Phlebovirus; Phylogeny; Prevalence; Rhipicephalus; Sequence Analysis, DNA; Tick-Borne Diseases; Zambia
PubMed: 33475831
DOI: 10.1007/s00705-020-04924-9 -
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 -
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 -
Acta Medica Portuguesa Oct 2021Toscana virus (TOSV) is an emerging sandfly-borne virus within the Phlebovirus genus. Although most infections caused by this virus present as asymptomatic or with...
INTRODUCTION
Toscana virus (TOSV) is an emerging sandfly-borne virus within the Phlebovirus genus. Although most infections caused by this virus present as asymptomatic or with minimal symptomatology, TOSV may emerge as a febrile disease or sporadic cases of neurological disease such as meningitis or meningoencephalitis. This pathogen is distributed throughout the Mediterranean basin, along with the spatial distribution of its recognized sandfly vector, Phlebotomus perniciosus. Portugal, after Italy, was the second country considered endemic for this virus, with the first case of acquired infection published in 1985. Although little is known about the circulation of this virus in Portugal, the laboratory diagnosis of TOSV is available at the Centre for Vectors and Infectious Diseases Research of the National Institute of Health Dr. Ricardo Jorge (CEVDI/INSA), since 2007. The aim of this study is to report the results of the diagnosis of TOSV at the CEVDI/INSA, between 2009 and 2018.
MATERIAL AND METHODS
The diagnosis of TOSV in the CEVDI/INSA is included in the arboviruses and vector-borne neurotropic viruses panels or can be performed, when specified, for TOSV only. Direct detection is made in cerebrospinal fluid samples and is available for TOSV by specific real-time reverse transcription polymerase chain reaction followed by conventional real-time reverse transcription polymerase chain reaction for sequencing purposes, if positive. For indirect diagnosis, performed in serum samples, an in-house immunofluorescence assay for the detection of IgM and IgG antibodies against TOSV is used. A commercial immunofluorescence assay consisting in a mosaic of four phleboviruses is also available, in which, in addition to TOSV, antibody detection for sandfly fever Naples virus, sandfly fever Sicilian virus and sandfly fever Cyprus virus can be done. All diagnostic tests requested by clinicians to the CEVDI/INSA for arboviruses, neurotropic viruses and/or TOSV between January 2009 and December 2018, were included in this study.
RESULTS
During the study period, the CEVDI/INSA received samples from 608 patients with diagnostic requests for TOSV. Five acute TOSV infections and one acute sandfly fever Sicilian virus infection were confirmed in serum samples. Three other patients had serological evidence of previous contact with the virus. Two of the six patients with acute infection developed febrile syndrome, and the other four presented with neurological disease: meningitis (n = 2), meningoencephalitis (n = 1) and severe depression of consciousness (n = 1). These infections were most likely acquired in the districts of Faro (3), Lisbon (2) and Setúbal (1).
DISCUSSION
In Portugal, the number of laboratory diagnostic requests for TOSV is low when compared to the numbers of requests for other less prevalent vector-borne viruses. The Faro district presented the highest number of TOSV-specific diagnostic requests which seems to indicate a higher level of recognition by clinicians in that region. Febrile syndrome and neurological disease were the clinical manifestations that were present in acute cases. In this study, in addition to the Faro district, recent infections were also detected in the districts of Lisbon and Setúbal. It is probable that TOSV may be distributed throughout the mainland territory since its main vector is present from north to south. In 2017, the sandfly fever Sicilian virus was associated for the first time with human disease in our country, thus alerting to the circulation of this phlebovirus.
CONCLUSION
Even though the number of identified cases in Portugal is low, TOSV circulates and causes disease in our country. The diagnosis of this and other phleboviruses should not be neglected in the differential diagnosis of febrile syndrome and viral meningitis and meningoencephalitis, especially during the warmer months, when the vector's activity is higher.
Topics: Antibodies, Viral; Diagnosis, Differential; Humans; Immunoglobulin G; Portugal; Sandfly fever Naples virus
PubMed: 34051876
DOI: 10.20344/amp.13308 -
Virology Apr 2021The heartland virus (HRTV) is a novel phlebovirus that causes severe infections in the USA and closely related to the severe fever thrombocytopenia syndrome virus...
The heartland virus (HRTV) is a novel phlebovirus that causes severe infections in the USA and closely related to the severe fever thrombocytopenia syndrome virus (SFTSV), a causative agent for SFTS in Asia. The entry mechanisms of HRTV remain unclear. Here, we developed the pseudotyped vesicular stomatitis virus bearing the HRTV glycoprotein (GP) (HRTVpv), and the antigenicity and the entry mechanisms of HRTV were analyzed. HRTVpv was neutralized by anti-SFTSV Gc antibody, but not the anti-SFTSV Gn antibodies. Entry of HRTVpv to cells was inhibited by bafilomycin A1 and dynasore, and but it was enhanced in cells overexpressed with C-type lectins. Production of infectious HRTVpv and SFTSVpv was reduced by Nn-DNJ, α-glucosidase inhibitor. The entry of HRTV occurs via pH- and dynamin-dependent endocytosis. Furthermore, Nn-DNJ may be a possible therapeutic agent against HRTV and SFTSV.
Topics: 1-Deoxynojirimycin; Animals; Bunyaviridae Infections; Cell Line; Cricetinae; Haplorhini; Humans; Mice; Phlebovirus; Vesicular Stomatitis; Vesiculovirus; Viral Envelope Proteins; Virus Internalization
PubMed: 33561699
DOI: 10.1016/j.virol.2020.10.006