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Der Hautarzt; Zeitschrift Fur... Nov 2018A 45-year-old woman presented at the outpatient department of a center for tropical diseases with fever, diarrhea, headache, myalgia, malaise, and an itchy papular... (Review)
Review
A 45-year-old woman presented at the outpatient department of a center for tropical diseases with fever, diarrhea, headache, myalgia, malaise, and an itchy papular rash. She had been on holiday with her family for 11 days in a mountain village in northern Cyprus. The place was infested with a lot of small, stinging flies or mosquitoes. She and her family became sick after they returned home. The physical examination was normal apart from the rash on the inside of the extremities. Significantly elevated transaminases and a slightly increased C‑reactive protein level were found in the blood examination. Considering the country of travel, the report of the "stinging flies" and the clinical presentation, sandfly fever was also taken into account as a differential diagnosis for the hepatitis. Antibodies to the sandfly fever Sicilian virus (SFSV) were detected. They showed the typical dynamics during the course of the illness and thus "pappataci fever" was diagnosed. The case report and a short review of up-to-date literature is meant encourage consideration of phlebovirus infection as a possible differential diagnosis in travelers or refugees suffering from severe febrile hepatitis and rash or aseptic viral meningitis after their stay in the Mediterranean area.
Topics: Animals; Antibodies, Viral; Diagnosis, Differential; Exanthema; Female; Humans; Middle Aged; Phlebotomus Fever; Phlebovirus; Travel
PubMed: 30151597
DOI: 10.1007/s00105-018-4251-1 -
Viruses Nov 2023Rift Valley fever phlebovirus (RVFV) is a zoonotic pathogen that causes Rift Valley fever (RVF) in livestock and humans. Currently, there is no licensed human vaccine or...
Rift Valley fever phlebovirus (RVFV) is a zoonotic pathogen that causes Rift Valley fever (RVF) in livestock and humans. Currently, there is no licensed human vaccine or antiviral drug to control RVF. Although multiple species of animals and humans are vulnerable to RVFV infection, host factors affecting susceptibility are not well understood. To identify the host factors or genes essential for RVFV replication, we conducted CRISPR-Cas9 knockout screening in human A549 cells. We then validated the putative genes using siRNA-mediated knock-downs and CRISPR-Cas9-mediated knock-out studies. The role of a candidate gene in the virus replication cycle was assessed by measuring intracellular viral RNA accumulation, and the virus titers were analyzed using plaque assay or TCID assay. We identified approximately 900 genes with potential involvement in RVFV infection and replication. Further evaluation of the effect of six genes on viral replication using siRNA-mediated knock-downs revealed that silencing two genes ( and ) significantly impaired RVFV replication. For further analysis, we focused on the gene since the role of the gene in RVFV replication was previously described in detail. knockout A549 cell lines were generated and used to dissect the effect of on a bunyavirus, RVFV, and an orthobunyavirus, La Crosse encephalitis virus (LACV). We observed significant effects of knockout cells on both intracellular RVFV RNA levels and viral titers. At the intracellular RNA level, affected RVFV replication at a later phase of its replication cycle (24 h) when compared with the LACV replication, which was affected in an earlier replication phase (12 h). In summary, we identified as an essential host factor for the replication of two different viruses, RVFV and LACV, both of which belong to the order. Future studies will investigate the mechanistic role through which facilitates phlebovirus replication.
Topics: Animals; Humans; Rift Valley Fever; Rift Valley fever virus; Phlebovirus; Virus Replication; RNA, Small Interfering; Adaptor Proteins, Signal Transducing
PubMed: 38005928
DOI: 10.3390/v15112251 -
Enfermedades Infecciosas Y... 2021The genera Phlebovirus transmitted by Diptera belonging to the Psychodidae family are a cause of self-limited febrile syndrome in the Mediterranean basin in summer and... (Review)
Review
The genera Phlebovirus transmitted by Diptera belonging to the Psychodidae family are a cause of self-limited febrile syndrome in the Mediterranean basin in summer and autumn. Toscana virus can also cause meningitis and meningoencephalitis. In Spain, Toscana, Granada, Naples, Sicily, Arbia and Arrabida-like viruses have been detected. The almost widespread distribution of Phlebotomus genus vectors, and especially Phlebotomus perniciosus, in which several of these viruses have been detected, makes it very likely that there will be regular human infections in our country, with this risk considered moderate for Toscana virus and low for the other ones, in areas with the highest vector activity. Most of the infections would be undiagnosed, while only Toscana virus would have a greater impact due to the potential severity of the illness.
Topics: Animals; Humans; Insect Vectors; Phlebovirus; Psychodidae; Sandfly fever Naples virus; Spain
PubMed: 34353512
DOI: 10.1016/j.eimce.2021.05.001 -
European Journal of Clinical... Jan 2022Toscana virus (TOSV) is emergent in the Mediterranean region and responsible for outbreaks of encephalitis or meningoencephalitis. Sicilian phlebovirus (SFSV) cause...
Toscana virus (TOSV) is emergent in the Mediterranean region and responsible for outbreaks of encephalitis or meningoencephalitis. Sicilian phlebovirus (SFSV) cause epidemics of febrile illness during the summer. The aim of this study was to evaluate the presence of antibodies against TOSV and SFSV in humans in the southwest of Portugal. Neutralizing antibodies to TOSV and SFSV were respectively detected in 5.3% and 4.3% out of 400 human sera tested highlighting the need to increase public health awareness regarding phleboviruses and to include them in the differential diagnosis in patients presenting with fever of short duration and neurological manifestations.
Topics: Adolescent; Adult; Aged; Antibodies, Neutralizing; Antibodies, Viral; Female; Humans; Male; Middle Aged; Phlebotomus Fever; Phlebovirus; Portugal; Sandfly fever Naples virus; Seasons; Seroepidemiologic Studies; Young Adult
PubMed: 34389911
DOI: 10.1007/s10096-021-04332-0 -
Viruses Jul 2021In the last two decades, molecular surveys of arboviruses have enabled the identification of several new viruses, contributing to the knowledge of viral diversity and...
In the last two decades, molecular surveys of arboviruses have enabled the identification of several new viruses, contributing to the knowledge of viral diversity and providing important epidemiological data regarding possible new emerging viruses. A combination of diagnostic assays, Illumina sequencing and phylogenetic inference are here used to characterize two new strains isolated from sandflies collected in the Arrábida region, Portugal. Whole genome sequence analysis enabled their identification as reassortants and the recognition of genomic variants co-circulating in Portugal. Much is still unknown about the life cycle, geographic range, evolutionary forces and public health importance of these viruses in Portugal and elsewhere, and more studies are needed.
Topics: Animals; Female; Genome, Viral; High-Throughput Nucleotide Sequencing; Phlebovirus; Phylogeny; Portugal; Psychodidae; RNA, Viral; Whole Genome Sequencing
PubMed: 34372617
DOI: 10.3390/v13071412 -
Virus Research Jul 2023A newly discovered tick-borne virus called the severe fever with thrombocytopenia syndrome virus (SFTSV) can cause the severe fever with thrombocytopenia syndrome...
A newly discovered tick-borne virus called the severe fever with thrombocytopenia syndrome virus (SFTSV) can cause the severe fever with thrombocytopenia syndrome (SFTS). The mortality and incidence rate of SFTS patients remain extremely high due to the fast global dissemination of its arthropod vectors, and the mechanism of viral pathogenesis remains largely unknown. In this study, high-throughput RNA sequencing (RNA-Seq) was used to sequence HEK 293 cells treated with SFTSV at four time points. 115, 191, 259, and 660 differentially expressed genes (DEGs) were identified at 6, 12, 24, and 48 h post-infection, respectively. We found that SFTSV infection induced the expression of genes responsible for numerous cytokine-related pathways, including TNF, CXCL1, CXCL2, CXCL3, CXCL8, CXCL10, and CCL20. With the extension of infection time, the expression of most genes involved in these pathways increased significantly, indicating the host's inflammatory response to SFTSV. Moreover, the expression levels of GNA13, ARHGEF12, RHOA, ROCK1, and MYL12A, elements of the platelet activation signaling pathway, were downregulated during SFTSV infection, suggesting that the SFTSV infection may cause thrombocytopenia by inhibiting platelet activation. Our results contribute to further understanding the interaction between SFTSV and the host.
Topics: Humans; Severe Fever with Thrombocytopenia Syndrome; Bunyaviridae Infections; HEK293 Cells; Phlebovirus; Signal Transduction; rho-Associated Kinases
PubMed: 37211158
DOI: 10.1016/j.virusres.2023.199138 -
Current Opinion in Virology Apr 2018Severe Fever with Thrombocytopenia Syndrome (SFTS) is a new emerging tick-borne disease caused by the phlebovirus, SFTS virus (SFTSV). The virus was discovered in... (Review)
Review
Severe Fever with Thrombocytopenia Syndrome (SFTS) is a new emerging tick-borne disease caused by the phlebovirus, SFTS virus (SFTSV). The virus was discovered in central China in 2009 and has since been identified in both Japan and South Korea. Significant progress has been made on the molecular biology of the virus, and this has been used to develop diagnostic assays and reagents. Less progress has been made on the epidemiology, maintenance and transmission, clinical manifestations, immunological responses, and treatment regimens. A number of animal models have been investigated but, to date, none recapitulate all the clinical manifestations seen in humans. Vaccine development is at an early discovery phase.
Topics: Animals; Disease Models, Animal; Host-Pathogen Interactions; Humans; Immunity; Models, Molecular; Phlebotomus Fever; Phlebovirus; Phylogeny; Protein Conformation; RNA, Viral; Viral Proteins; Viral Vaccines
PubMed: 29642053
DOI: 10.1016/j.coviro.2018.03.005 -
Viruses Apr 2021Severe fever with thrombocytopenia syndrome (SFTS), which is caused by SFTS virus (SFTSV), is a tick-borne emerging zoonosis with a high case-fatality rate. At present,... (Review)
Review
Severe fever with thrombocytopenia syndrome (SFTS), which is caused by SFTS virus (SFTSV), is a tick-borne emerging zoonosis with a high case-fatality rate. At present, there is no approved SFTS vaccine, although the development of a vaccine would be one of the best strategies for preventing SFTS. This article focused on studies aimed at establishing small animal models of SFTS that are indispensable for evaluating vaccine candidates, developing these vaccine candidates, and establishing more practical animal models for evaluation. Innate immune-deficient mouse models, a hamster model, an immunocompetent ferret model and a cat model have been developed for SFTS. Several vaccine candidates for SFTS have been developed, and their efficacy has been confirmed using these animal models. The candidates consist of live-attenuated virus-based, viral vector-based, or DNA-based vaccines. SFTS vaccines are expected to be used for humans and companion dogs and cats. Hence for practical use, the vaccine candidates should be evaluated for efficacy using not only nonhuman primates but also dogs and cats. There is no practical nonhuman primate model of SFTS; however, the cat model is available to evaluate the efficacy of these candidate SFTS vaccines on domesticated animals.
Topics: Animals; Cat Diseases; Cats; Cricetinae; Disease Models, Animal; Dog Diseases; Dogs; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Phlebovirus; Primates; Severe Fever with Thrombocytopenia Syndrome; Viral Vaccines
PubMed: 33917632
DOI: 10.3390/v13040627 -
Reviews in Medical Virology Mar 2017Sandfly-transmitted phleboviruses are globally spread agents causing febrile diseases and central nervous system infections. The activity of pathogenic phleboviruses, as... (Review)
Review
Sandfly-transmitted phleboviruses are globally spread agents causing febrile diseases and central nervous system infections. The activity of pathogenic phleboviruses, as well as several novel strains, has been reported from Turkey, a transboundary country connecting Asia, Europe, and Africa with suitable habitats for sandflies. This study overviews all published data on phleboviruses from Turkey and evaluates the impact from the virological, epidemiological, and public health perspectives. A systematic review of Web-based global and local resources was performed. Comparison and phylogenetic analyses of particular phlebovirus sequences were also undertaken. Through the evaluation of 1693 international and regional entries, 31 manuscripts providing data on case reports or outbreaks, serological surveillance, animal infections and exposure, virus characterization, vector surveillance, and/or diagnostics were accessed. Detailed information on 5 novel phleboviruses completely or partially characterized during 2008-2015 as well as on clinical and epidemiological features of major phleboviruses established as human pathogens such as Toscana virus and sandfly fever Sicilian virus has been compiled. The ongoing activity of these agents, as indicated by consistently reported symptomatic cases and confirmed exposure in vertebrates including humans, was noted. The circulation in the Anatolian peninsula of phleboviruses with surprising diversity as well as distinct virus species is documented. Specific phlebovirus strains constitute a public health threat for local populations and travelers and must be considered in the diagnostic workup of clinically compatible cases. Human health impact and epidemiological aspects of certain viruses require further investigation via intensive surveillance.
Topics: Animals; Asia; Humans; Phlebotomus Fever; Phlebovirus; Psychodidae; Vertebrates
PubMed: 27531681
DOI: 10.1002/rmv.1898 -
Viruses Sep 2018First identified in two Missouri farmers exhibiting low white-blood-cell and platelet counts in 2009, Heartland virus (HRTV) is genetically closely related to severe... (Review)
Review
First identified in two Missouri farmers exhibiting low white-blood-cell and platelet counts in 2009, Heartland virus (HRTV) is genetically closely related to severe fever with thrombocytopenia syndrome virus (SFTSV), a tick-borne phlebovirus producing similar symptoms in China, Korea, and Japan. Field isolations of HRTV from several life stages of unfed, host-seeking , the lone star tick, implicated it as a putative vector capable of transstadial transmission. Laboratory vector competence assessments confirmed transstadial transmission of HRTV, demonstrated vertical infection, and showed co-feeding infection between . A vertical infection rate of 33% from adult females to larvae in the laboratory was observed, while only one of 386 pools of molted nymphs (1930) reared from co-feeding larvae was positive for HRTV (maximum-likelihood estimate of infection rate = 0.52/1000). Over 35 human HRTV cases, all within the distribution range of , have been documented. Serological testing of wildlife in areas near the index human cases, as well as in widely separated regions of the eastern United States where occur, indicated many potential hosts such as raccoons and white-tailed deer. Attempts, however, to experimentally infect mice, rabbits, hamsters, chickens, raccoons, goats, and deer failed to produce detectable viremia. Immune-compromised mice and hamsters are the only susceptible models. Vertical infection augmented by co-feeding transmission could play a role in maintaining the virus in nature. A more complete assessment of the natural transmission cycle of HRTV coupled with serosurveys and enhanced HRTV disease surveillance are needed to better understand transmission dynamics and human health risks.
Topics: Animals; Bunyaviridae Infections; Disease Management; Disease Models, Animal; Disease Vectors; Host-Pathogen Interactions; Humans; Phlebovirus; Phylogeny; Population Surveillance; United States
PubMed: 30223439
DOI: 10.3390/v10090498