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Emerging Infectious Diseases Apr 2020We conducted an epidemiologic study of severe fever with thrombocytopenia syndrome (SFTS) in Japan during 2013-2017. Of 303 cases reported during that period, 133 (44%)...
We conducted an epidemiologic study of severe fever with thrombocytopenia syndrome (SFTS) in Japan during 2013-2017. Of 303 cases reported during that period, 133 (44%) were included in this study. The median time between onset of illness and diagnosis of SFTS shortened, from 11.5 to 3.0 days, but the case-fatality rate remained high, at 27%. In 64 patients (48%), a close contact with companion animals was reported within 2 weeks of disease onset. Of these 64 patients, 40 were surveyed further, and we confirmed that 3 had direct contact with body fluids of ill companion animals; 2 had direct contact with the saliva of an ill feral cat or pet dog. These patients reported no history of tick bite, suggesting that ill companion animals might be a source of SFTS virus transmission. Direct contact with the body fluids of ill companion animals should be avoided.
Topics: Animals; Body Fluids; Bunyaviridae Infections; Cats; Dogs; Humans; Japan; Phlebotomus Fever; Phlebovirus; Severe Fever with Thrombocytopenia Syndrome; Tick Bites
PubMed: 32186502
DOI: 10.3201/eid2604.191011 -
Emerging Microbes & Infections May 2018Tick-borne viral diseases have attracted much attention in recent years because of their increasing incidence and threat to human health. Severe fever with...
Tick-borne viral diseases have attracted much attention in recent years because of their increasing incidence and threat to human health. Severe fever with thrombocytopenia syndrome phlebovirus (SFTSV) and Heartland virus (HRTV) were recently identified as tick-borne phleboviruses (TBPVs) in Asia and the United States, respectively, and are associated with severe human diseases with similar clinical manifestations. In this study, we report the first identification and isolation of a novel TBPV named Guertu virus (GTV) from Dermacentor nuttalli ticks in Xinjiang Province, China, where TBPVs had not been previously discovered. Genome sequence and phylogenetic analyses showed that GTV is closely related to SFTSV and HRTV and was classified as a member of the genus Phlebovirus, family Phenuiviridae, order Bunyavirales. In vitro and in vivo investigations of the properties of GTV demonstrated that it was able to infect animal and human cell lines and can suppress type I interferon signaling, similar to SFTSV, that GTV nucleoprotein (NP) can rescue SFTSV replication by replacing SFTSV NP, and that GTV infection can cause pathological lesions in mice. Moreover, a serological survey identified antibodies against GTV from serum samples of individuals living in Guertu County, three of which contained neutralizing antibodies, suggesting that GTV can infect humans. Our findings suggested that this virus is a potential pathogen that poses a threat to animals and humans. Further studies and surveillance of GTV are recommended to be carried out in Xinjiang Province as well as in other locations.
Topics: Animals; Cell Line, Tumor; Chlorocebus aethiops; Dermacentor; Genome, Viral; HEK293 Cells; Hep G2 Cells; Humans; Interferon Type I; Mice; Mice, Inbred C57BL; Nucleoproteins; Phlebotomus Fever; Phlebovirus; Phylogeny; Vero Cells; Virus Replication
PubMed: 29802259
DOI: 10.1038/s41426-018-0093-2 -
Viruses Apr 2021Viral infections are one of the leading causes in human mortality and disease. Broad-spectrum antiviral drugs are a powerful weapon against new and re-emerging viruses....
Viral infections are one of the leading causes in human mortality and disease. Broad-spectrum antiviral drugs are a powerful weapon against new and re-emerging viruses. However, viral resistance to existing broad-spectrum antivirals remains a challenge, which demands development of new broad-spectrum therapeutics. In this report, we showed that fludarabine, a fluorinated purine analogue, effectively inhibited infection of RNA viruses, including Zika virus, Severe fever with thrombocytopenia syndrome virus, and Enterovirus A71, with all IC values below 1 μM in Vero, BHK21, U251 MG, and HMC3 cells. We observed that fludarabine has shown cytotoxicity to these cells only at high doses indicating it could be safe for future clinical use if approved. In conclusion, this study suggests that fludarabine could be developed as a potential broad-spectrum anti-RNA virus therapeutic agent.
Topics: Animals; Antiviral Agents; Cell Line; Cell Survival; Cells, Cultured; Enterovirus A, Human; Humans; Phlebovirus; RNA Viruses; Vidarabine; Virus Replication; Zika Virus
PubMed: 33925713
DOI: 10.3390/v13050774 -
Virologica Sinica Feb 2024Severe fever with thrombocytopenia syndrome (SFTS) caused by the SFTS virus (SFTSV) is an emerging disease in East Asia with a fatality rate of up to 30%. However, the...
Severe fever with thrombocytopenia syndrome (SFTS) caused by the SFTS virus (SFTSV) is an emerging disease in East Asia with a fatality rate of up to 30%. However, the viral-host interaction of SFTSV remains largely unknown. The heat-shock protein 90 (Hsp90) family consists of highly conserved chaperones that fold and remodel proteins and has a broad impact on the infection of many viruses. Here, we showed that Hsp90 is an important host factor involved in SFTSV infection. Hsp90 inhibitors significantly reduced SFTSV replication, viral protein expression, and the formation of inclusion bodies consisting of nonstructural proteins (NSs). Among viral proteins, NSs appeared to be the most reduced when Hsp90 inhibitors were used, and further analysis showed that their translation was affected. Co-immunoprecipitation of NSs with four isomers of Hsp90 showed that Hsp90 β specifically interacted with them. Knockdown of Hsp90 β expression also inhibited replication of SFTSV. These results suggest that Hsp90 β plays a critical role during SFTSV infection and could be a potential target for the development of drugs against SFTS.
Topics: Humans; Severe Fever with Thrombocytopenia Syndrome; Phlebovirus; Host Microbial Interactions; Bunyaviridae Infections
PubMed: 38008382
DOI: 10.1016/j.virs.2023.11.008 -
Emerging Infectious Diseases Apr 2022Report of a human death and exposure of white-tailed deer to Heartland virus (HRTV) in Georgia, USA, prompted the sampling of questing ticks during 2018-2019 in 26 sites...
Report of a human death and exposure of white-tailed deer to Heartland virus (HRTV) in Georgia, USA, prompted the sampling of questing ticks during 2018-2019 in 26 sites near where seropositive deer were captured and the residence of the human case-patient. We processed 9,294 Amblyomma americanum ticks in pools by virus isolation in Vero E6 cells and reverse transcription PCR. Positive pools underwent whole-genome sequencing. Three pools were positive for HRTV (minimum infection rate 0.46/1,000 ticks) and none for Bourbon virus. Cell cultures confirmed HRTV presence in 2 pools. Genome sequencing, achieved for the 3 HRTV isolates, showed high similarity among samples but marked differences with previously sequenced HRTV isolates. The isolation and genomic characterization of HRTV from A. americanum ticks in Georgia confirm virus presence in the state. Clinicians and public health professionals should be aware of this emerging tickborne pathogen.
Topics: Amblyomma; Animals; Deer; Georgia; Humans; Phlebovirus; Ticks
PubMed: 35318917
DOI: 10.3201/eid2804.211540 -
Journal of Virological Methods May 2023Rift Valley fever phlebovirus (RVFV) is an emerging, mosquito-borne, zoonotic pathogen. Real time RT-qPCR genotyping (GT) assays were developed to differentiate between...
Rift Valley fever phlebovirus (RVFV) is an emerging, mosquito-borne, zoonotic pathogen. Real time RT-qPCR genotyping (GT) assays were developed to differentiate between two RVFV wild-type strains (128B-15 and SA01-1322) and a vaccine strain (MP-12). The GT assay uses a one-step RT-qPCR mix, with two different RVFV strain-specific primers (either forward or reverse) with long or short G/C tags and a common primer (either forward or reverse) for each of the 3 genomic segments. The GT assay produces PCR amplicons with unique melting temperatures that are resolved in a post PCR melt curve analysis for strain identification. Furthermore, a strain specific RT-qPCR (SS-PCR) assay was developed to allow for specific detection of low titer RVFV strains in mixed RVFV samples. Our data shows that the GT assays are capable of differentiating L, M, and S segments of RVFV strains 128B-15 versus MP-12, and 128B-15 versus SA01-1322. The SS-PCR assay results revealed that it can specifically amplify and detect a low titer MP-12 strain in mixed RVFV samples. Overall, these two novel assays are useful as screening tools for determining reassortment of the segmented RVFV genome during co-infections, and could be adapted and applied for other segmented pathogens of interest.
Topics: Animals; Humans; Rift Valley Fever; Rift Valley fever virus; Genotype; Phlebovirus; Polymerase Chain Reaction
PubMed: 36801236
DOI: 10.1016/j.jviromet.2023.114693 -
Frontiers in Public Health 2022To explore the influence of climatic, environmental and socioeconomic factors on SFTS occurrence in Shandong Province, China.
OBJECTIVE
To explore the influence of climatic, environmental and socioeconomic factors on SFTS occurrence in Shandong Province, China.
METHODS
We used generalized additive model to estimate the association between SFTS cases and climatic factors, environmental factors and socioeconomic factors, including annual average temperature, precipitation, land cover, normalized difference vegetation index, altitude, population density, meat production, milk production, and gross domestic product (GDP).
RESULTS
There were a total of 4,830 cases reported in 100 (70.9%) counties and districts in Shandong Province from 2010 to 2020. The results showed that the annual average temperature, precipitation, forest and grassland coverage rate, altitude and meat production (square root transform) had a reversed "V" relationship with SFTS occurrence, with the inflection points around 12.5-13.0°C in temperature, around 650 mm in precipitation, around 0.3 in forest and grassland coverage rate, around 300 m in altitude, and around 200-300 tons in meat production (square root transform), respectively. SFTS occurrence had a "V" relationship with milk production (square root transform) and GDP (square root transform), with the inflection points around 100-200 tons in milk production (square root transform), and around 150,000-200,000 yuan in GDP (square root transform), respectively.
CONCLUSIONS
Climatic, environmental, and socioeconomic factors contributed to the heterogeneous distribution of SFTS in Shandong Province, and the influence of these factors on SFTS occurrence was nonlinear.
Topics: China; Humans; Phlebovirus; Severe Fever with Thrombocytopenia Syndrome; Temperature; Thrombocytopenia
PubMed: 35284401
DOI: 10.3389/fpubh.2022.844220 -
MSphere Sep 2020Sandfly-transmitted phleboviruses (family , order ) are associated with febrile illness and infections of the nervous system in humans. These viruses are almost...
Sandfly-transmitted phleboviruses (family , order ) are associated with febrile illness and infections of the nervous system in humans. These viruses are almost exclusively found in tropical areas of the New World and restricted to semiarid and temperate zones in the Old World. Here, we discovered seven strains of four previously unknown phleboviruses, named Bogoria virus (BOGV), Embossos virus (EMRV), Kiborgoch virus (KBGV), and Perkerra virus (PERV), as well as the recently discovered Ntepes virus, in sandflies collected in the Kenyan Rift Valley. The genomes have a tripartite organization with conserved termini typical of phleboviruses. LOBV, PERV, and EMBV showed low similarity to known phleboviruses, with less than 55% pairwise amino acid identities in the RNA-directed RNA polymerase (RdRp) proteins, and defined a highly diversified monophyletic clade in sister relationship to the sandfly fever Sicilian serocomplex. All three viruses failed to react with sandfly fever Sicilian virus antisera in recombinant immunofluorescence assays (rIFA), suggesting that the viruses belong to a yet-unknown serogroup. In contrast, KBGV was closely related to Toscana virus (84% identity of RdRp proteins) and shared a most recent common ancestor with the clade comprising sandfly fever Naples and Toscana viruses. KBGV reacted with sandfly fever Naples and Toscana virus antisera in rIFA. The genetic diversity of the detected viruses and their phylogenetic positions implies that the Old World sandfly-borne phleboviruses originated from sub-Saharan Africa. Importantly, our findings suggest that diseases associated with sandfly-borne phlebovirus infections may also affect the Kenyan population. Studies on the genetic diversity of arthropod-borne viruses circulating in rural regions can provide critical early indications on new emerging viruses essential for global epidemic preparedness. In this study, we describe the discovery of four phleboviruses in sandflies from the Kenyan Rift Valley. The novel viruses are related to the two medically important serocomplexes, sandfly fever Naples and sandfly fever Sicilian, that are associated with febrile illness and neuroinvasive infections and which were previously not known to occur in sub-Saharan Africa. Knowledge on the occurrence of sandfly-borne phleboviruses in Kenya and elsewhere in Africa can help to decipher their contributions in the etiologies of fevers of unknown origin in patients. Our findings on five genetically diverse phleboviruses detected in Kenya suggest that the common ancestor of Old World phleboviruses existed in sub-Saharan Africa, a hot spot for emerging arboviruses.
Topics: Animals; Evolution, Molecular; Genetic Variation; Humans; Kenya; Phlebotomus Fever; Phlebovirus; Phylogeny; Psychodidae; Sandfly fever Naples virus; Viral Proteins
PubMed: 32878929
DOI: 10.1128/mSphere.00598-20 -
Viruses Jul 2021The detection of phleboviruses (family: ) in human samples is challenged by the overall diversity and genetic complexity of clinically relevant strains, their...
The detection of phleboviruses (family: ) in human samples is challenged by the overall diversity and genetic complexity of clinically relevant strains, their predominantly nondescript clinical associations, and a related lack of awareness among some clinicians and laboratorians. Here, we seek to inform the detection of human phlebovirus infections by providing a brief introduction to clinically relevant phleboviruses, as well as key targets and approaches for their detection. Given the diversity of pathogens within the genus, this report focuses on diagnostic attributes that are generally shared among these agents and should be used as a complement to, rather than a replacement of, more detailed discussions on the detection of phleboviruses at the individual virus level.
Topics: Animals; Antibodies, Viral; Genetic Variation; Humans; Phlebotomus Fever; Phlebovirus; Phylogeny; Psychodidae; Viremia
PubMed: 34452365
DOI: 10.3390/v13081500 -
Parasites & Vectors Jul 2018High throughput sequencing (HTS) boosted the discovery of novel viruses and new variants of known viruses. Here we investigated the presence of viruses in 12 pools of...
BACKGROUND
High throughput sequencing (HTS) boosted the discovery of novel viruses and new variants of known viruses. Here we investigated the presence of viruses in 12 pools of sand flies captured in three climatic periods in RAPELD grids at Rio Claro, Chapada dos Guimarães and at Pirizal, North Pantanal, Mato Grosso State, Midwestern Brazil by HTS, viral isolation of a putative Phlebovirus positive pool in Vero cells, RT-PCR and transmission electron microscopy (TEM).
RESULTS
One pool containing three Lutzomyia (Lutzomyia) longipalpis sand flies captured in the transitional climatic period in North Pantanal showed a tripartite genomic sequence of a putative novel Phlebovirus belonging to the phlebotomus fever serogroup. Phylogenetic analysis revealed this virus is closely related and share a common ancestor with phleboviruses included in the same clade: Chagres, Urucuri and Uriurana virus. RNA-dependent RNA polymerase (RdRP) presented 60%, 59% and 58% of amino-acid (aa) similarity with these phleboviruses, respectively. Similarity of Nucleoprotein and NSs protein codified by ambissense strategy of segment S was of 49% and 37%, respectively, with the proteins of the closest phlebovirus, Uriurana virus. Glycoproteins (G1, G2) and NSm protein presented 49% and 48% aa similarity with Chagres and Uriurana virus, respectively. Uriurana virus was isolated from sand flies in Brazilian Amazon and Urucuri from rodents in Utinga forest, Pará State. Chagres virus is an arbovirus responsible for outbreaks of febrile illness in Panama. This phlebovirus was isolated in Vero cells, confirmed by TEM and RT-PCR for the L segment of the virus, and named Viola phlebovirus.
CONCLUSIONS
HTS, viral isolation, RT-PCR and TEM showed the presence of one virus in sand flies from North Pantanal with identity to a putative novel Phlebovirus from phlebotomus fever serogroup, named Viola phlebovirus.
Topics: Animals; Brazil; Chlorocebus aethiops; Phlebovirus; Phylogeny; Psychodidae; Vero Cells
PubMed: 29996902
DOI: 10.1186/s13071-018-2985-3