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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 -
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 -
Emerging Infectious Diseases May 2021We describe a series of severe neuroinvasive infections caused by Toscana virus, identified by real-time reverse transcription PCR testing, in 8 hospitalized patients in...
We describe a series of severe neuroinvasive infections caused by Toscana virus, identified by real-time reverse transcription PCR testing, in 8 hospitalized patients in Bucharest, Romania, during the summer seasons of 2017 and 2018. Of 8 patients, 5 died. Sequencing showed that the circulating virus belonged to lineage A.
Topics: Bunyaviridae Infections; Humans; Romania; Sandfly fever Naples virus
PubMed: 33900182
DOI: 10.3201/eid2705.204598 -
The American Journal of Tropical... Oct 2017Severe fever with thrombocytopenia syndrome (SFTS) is a newly recognized hemorrhagic fever disease found throughout Asia with a case fatality rate between 12% and 30%.... (Review)
Review
Severe fever with thrombocytopenia syndrome (SFTS) is a newly recognized hemorrhagic fever disease found throughout Asia with a case fatality rate between 12% and 30%. Since 2009, SFTS has been reported in China throughout 14 Chinese Provinces. In addition, SFTS has been recognized in South Korea and Japan with the first confirmed cases reported in 2012. A similar disease, caused by the closely related Heartland virus, was also reported in the United States in 2009. SFTS is caused by SFTS virus, a novel tick-borne virus in the family , genus . Unlike other mosquito- and sandfly-borne bunyaviruses, SFTS virus has not been extensively studied due to its recent emergence and many unknowns regarding its pathogenesis, life cycle, transmission, and options for therapeutics remains. In this review, we report the most current findings in SFTS virus research.
Topics: Animals; Arthropod Vectors; Asia; Bunyaviridae Infections; Communicable Diseases, Emerging; Humans; Phlebotomus Fever; Phlebovirus; Thrombocytopenia; Tick-Borne Diseases; Ticks; Zoonoses
PubMed: 28820686
DOI: 10.4269/ajtmh.16-0967 -
Microbiology Spectrum Oct 2022Blood-sucking ticks are obligate parasites and vectors of a variety of human and animal viruses. Some tick-borne viruses have been identified as pathogens of infectious...
Blood-sucking ticks are obligate parasites and vectors of a variety of human and animal viruses. Some tick-borne viruses have been identified as pathogens of infectious diseases in humans or animals, potentially imposing significant public health burdens and threats to the husbandry industry. Therefore, identifying the profiles of tick-borne viruses will provide valuable information about the evolution and pathogen ecology of tick-borne viruses. In this study, we investigated the viromes of parasitic ticks collected from the body surfaces of herbivores in Xinjiang Uyghur Autonomous Region and Inner Mongolia Autonomous Region of China, two regions in northwest China. By using a metatranscriptomic approach, 17 RNA viruses with high diversity in genomic organization and evolution were identified. Among them, nine are proposed to be novel species. The classified viruses belonged to six viral families, including , , , , , and , and unclassified viruses were also identified. In addition, although some viruses from different sampling locations shared significant similarities, the abundance and diversity of viruses notably varied among the different collection locations. This study demonstrates the diversity of tick-borne viruses in Xinjiang and Inner Mongolia and provides informative data for further study of the evolution and pathogenicity of these RNA viruses. Ticks are widely distributed in pastoral areas in northwestern China and act as vectors that carry and transmit a variety of pathogens, especially viruses. Our study revealed the diversity of tick viruses in Xinjiang and Inner Mongolia and uncovered the phylogenetic relationships of some RNA viruses, especially the important zoonotic tick-borne severe fever with thrombocytopenia syndrome virus in Inner Mongolia. These data suggest a complex and diverse evolutionary history and potential ecological factors associated with pathogenic viruses. The pathogenicity of these tick-borne viruses currently remains unclear. Therefore, future research should focus on evaluating the transmissability and pathogenicity of these tick-borne viruses.
Topics: Humans; Animals; Ticks; Phylogeny; Virome; Phlebovirus; RNA Viruses; China; Viruses; Tick-Borne Diseases
PubMed: 36214702
DOI: 10.1128/spectrum.01115-22 -
The Journal of Biological Chemistry Jun 2023Severe fever with thrombocytopenia syndrome virus (SFTSV), which has been reported in China, Korea, Japan, Vietnam, and Taiwan, is a causative agent of severe fever...
Severe fever with thrombocytopenia syndrome virus (SFTSV), which has been reported in China, Korea, Japan, Vietnam, and Taiwan, is a causative agent of severe fever thrombocytopenia syndrome. This virus has a high mortality and induces thrombocytopenia and leukocytopenia in humans, cats, and aged ferrets, whereas immunocompetent adult mice infected with SFTSV never show symptoms. Anti-SFTSV antibodies have been detected in several animals-including goats, sheep, cattle, and pigs. However, there are no reports of severe fever thrombocytopenia syndrome in these animals. Previous studies have reported that the nonstructural protein NSs of SFTSV inhibits the type I interferon (IFN-I) response through the sequestration of human signal transducer and activator of transcription (STAT) proteins. In this study, comparative analysis of the function of NSs as IFN antagonists in human, cat, dog, ferret, mouse, and pig cells revealed a correlation between pathogenicity of SFTSV and the function of NSs in each animal. Furthermore, we found that the inhibition of IFN-I signaling and phosphorylation of STAT1 and STAT2 by NSs depended on the binding ability of NSs to STAT1 and STAT2. Our results imply that the function of NSs in antagonizing STAT2 determines the species-specific pathogenicity of SFTSV.
Topics: Aged; Animals; Cattle; Dogs; Humans; Mice; Ferrets; Interferon Type I; Phlebovirus; Severe Fever with Thrombocytopenia Syndrome; Sheep; Signal Transduction; Swine; Thrombocytopenia; Viral Nonstructural Proteins
PubMed: 37187292
DOI: 10.1016/j.jbc.2023.104819 -
Nucleic Acids Research Feb 2023Severe fever with thrombocytopenia syndrome virus (SFTSV) is a phenuivirus that has rapidly become endemic in several East Asian countries. The large (L) protein of...
Severe fever with thrombocytopenia syndrome virus (SFTSV) is a phenuivirus that has rapidly become endemic in several East Asian countries. The large (L) protein of SFTSV, which includes the RNA-dependent RNA polymerase (RdRp), is responsible for catalysing viral genome replication and transcription. Here, we present 5 cryo-electron microscopy (cryo-EM) structures of the L protein in several states of the genome replication process, from pre-initiation to late-stage elongation, at a resolution of up to 2.6 Å. We identify how the L protein binds the 5' viral RNA in a hook-like conformation and show how the distal 5' and 3' RNA ends form a duplex positioning the 3' RNA terminus in the RdRp active site ready for initiation. We also observe the L protein stalled in the early and late stages of elongation with the RdRp core accommodating a 10-bp product-template duplex. This duplex ultimately splits with the template binding to a designated 3' secondary binding site. The structural data and observations are complemented by in vitro biochemical and cell-based mini-replicon assays. Altogether, our data provide novel key insights into the mechanism of viral genome replication by the SFTSV L protein and will aid drug development against segmented negative-strand RNA viruses.
Topics: Humans; Severe Fever with Thrombocytopenia Syndrome; Cryoelectron Microscopy; RNA, Viral; RNA-Dependent RNA Polymerase; Phlebovirus; Virus Replication; Genome, Viral
PubMed: 36651274
DOI: 10.1093/nar/gkac1249 -
Viruses Jan 2021Phleboviruses transmitted by phlebotomine sandflies are endemic in the Mediterranean basin. (TOSV), (SFSV), and (SFNV) are responsible of summer fever, with...
Phleboviruses transmitted by phlebotomine sandflies are endemic in the Mediterranean basin. (TOSV), (SFSV), and (SFNV) are responsible of summer fever, with well-known pathogenic potential for humans ranging from asymptomatic to mild fever, in addition to neuro-invasive infections during summer. Although TOSV, in particular, is a significant and well-known human pathogen, SFVs remain neglected, with many gaps in the relevant knowledge. Sero-epidemiological studies and case reports recently showed a geographical wider distribution than previously considered, although the real incidence of phleboviruses infections in the Mediterranean area is still unknown. Here we retrospectively evaluated the circulation of phleboviruses during summer seasons between 2007 and 2019 in 649 patients showing neurological symptoms using both molecular and serological approaches. We found that 42/649 (6.5%) subjects experienced phlebovirus infection and only 10/42 cases were detected by molecular assays, whereas the other 32/42 were identified using serological approaches, including neutralization assays. During the 2013 summer, an outbreak in the Lombardy region is described because the prevalence of phlebovirus infection reached 37.2% (19/51 subjects). Interestingly, only 5/19 (26.5%) reported traveling in endemic areas. Of note, no cross-neutralization was observed between different strains tested, showing the possibility to be reinfected by newly discovered phlebovirus strains. In conclusion, phlebovirus infections are still inadequately considered by physicians and are generally underestimated. However, based on our results, sandfly fever viruses should be routinely included in diagnostic panels during summer period, including in Northern Italy.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Animals; Antibodies, Neutralizing; Female; Humans; Immunoglobulin G; Immunoglobulin M; Italy; Male; Middle Aged; Phlebotomus Fever; Phlebovirus; RNA, Viral; Retrospective Studies; Seasons; Young Adult
PubMed: 33573092
DOI: 10.3390/v13020209 -
Protein & Cell Dec 2023
Topics: Humans; Severe Fever with Thrombocytopenia Syndrome; Phlebovirus
PubMed: 37038326
DOI: 10.1093/procel/pwad019 -
Scientific Reports Mar 2018Autophagy is essential for eukaryotic cell homeostasis and can perform both anti-viral and pro-viral roles depending on the kinds of viruses, cell types and cell...
Autophagy is essential for eukaryotic cell homeostasis and can perform both anti-viral and pro-viral roles depending on the kinds of viruses, cell types and cell environment. Severe fever with thrombocytopenia syndrome phlebovirus (SFTSV) is a newly discovered tick-borne virus in the Phenuiviridae family that causes a severe hemorrhagic fever disease in East Asia. In this study we determined interactions between SFTSV and autophagy. Our results showed that LC3-II (microtubule associated protein 1 light chain 3-II) protein accumulated from 4 h to 24 h after SFTSV infection compared to mock-infected Vero cells, and the use of E64d and pepstatin A did not affect the expression of LC3-II protein, which indicated that the increased LC3-II may be the result of inhibition of autophagic degradation caused by SFTSV infection. However, knockdown of LC3B promotes SFTSV replication, which indicated a negative role of LC3B protein in SFTSV replication. We also detected co-localization of SFTSV non-structure (NSs) protein with LC3B, p62 and Lamp2b respectively in SFTSV infected Vero cells, which indicated the possibility of selective autophagy or chaperone-mediated autophagy involving in SFTSV infection. Our results indicated that SFTSV infection promotes LC3 accumulation and several proteins of the autophagy pathway co-localize with NSs protein during SFTSV infection.
Topics: Animals; Autophagy; Chlorocebus aethiops; Host-Pathogen Interactions; Humans; Mice, Inbred BALB C; Microtubule-Associated Proteins; Phlebotomus Fever; Phlebovirus; Vero Cells; Viral Nonstructural Proteins; Virus Replication
PubMed: 29588492
DOI: 10.1038/s41598-018-23610-0