-
Infection, Genetics and Evolution :... Aug 2024Toscana Virus (TosV) was firstly isolated from phlebotomine in our Institute about fifty years ago. Later, in 1984-1985, TosV infection, although asymptomatic in most...
Toscana Virus (TosV) was firstly isolated from phlebotomine in our Institute about fifty years ago. Later, in 1984-1985, TosV infection, although asymptomatic in most cases, was shown to cause disease in humans, mainly fever and meningitis. By means of genetic analysis of part of M segment, we describe 3 new viral isolates obtained directly from cerebrospinal fluid or sera samples of patients diagnosed with TosV infection in July 2020 in Tuscany region. Phylogenesis was used to propose the clustering of TosV lineage A strains in 3 main groups, whereas deep mutational analysis based on 12 amino acid positions, allowed the identification of 9 putative strains. We discuss deep mutational analysis as a method to identify molecular signature of host adaptation and/or pathogenesis.
Topics: Humans; Italy; Phylogeny; Sandfly fever Naples virus; Genome, Viral; Evolution, Molecular; Genomics; Male
PubMed: 38830443
DOI: 10.1016/j.meegid.2024.105601 -
Proceedings of the National Academy of... Jun 2024Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with a high fatality rate of up to 30% caused by SFTS virus (SFTSV). However, no...
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with a high fatality rate of up to 30% caused by SFTS virus (SFTSV). However, no specific vaccine or antiviral therapy has been approved for clinical use. To develop an effective treatment, we isolated a panel of human monoclonal antibodies (mAbs). SF5 and SF83 are two neutralizing mAbs that recognize two viral glycoproteins (Gn and Gc), respectively. We found that their epitopes are closely located, and we then engineered them as several bispecific antibodies (bsAbs). Neutralization and animal experiments indicated that bsAbs display more potent protective effects than the parental mAbs, and the cryoelectron microscopy structure of a bsAb3 Fab-Gn-Gc complex elucidated the mechanism of protection. In vivo virus passage in the presence of antibodies indicated that two bsAbs resulted in less selective pressure and could efficiently bind to all single parental mAb-escape mutants. Furthermore, epitope analysis of the protective mAbs against SFTSV and RVFV indicated that they are all located on the Gn subdomain I, where may be the hot spots in the phleboviruses. Collectively, these data provide potential therapeutic agents and molecular basis for the rational design of vaccines against SFTSV infection.
Topics: Animals; Antibodies, Bispecific; Mice; Antibodies, Neutralizing; Phlebovirus; Humans; Antibodies, Viral; Glycoproteins; Antibodies, Monoclonal; Epitopes; Disease Models, Animal; Severe Fever with Thrombocytopenia Syndrome
PubMed: 38830098
DOI: 10.1073/pnas.2400163121 -
Scientific Reports May 2024Hard ticks are known vectors of various pathogens, including the severe fever with thrombocytopenia syndrome virus, Rickettsia spp., Coxiella burnetii, Borrelia spp.,...
Hard ticks are known vectors of various pathogens, including the severe fever with thrombocytopenia syndrome virus, Rickettsia spp., Coxiella burnetii, Borrelia spp., Anaplasma phagocytophilum, and Ehrlichia spp. This study aims to investigate the distribution and prevalence of tick-borne pathogens in southwestern Korea from 2019 to 2022. A total of 13,280 ticks were collected during the study period, with H. longicornis accounting for 86.1% of the collected ticks. H. flava, I. nipponensis and A. testudinarium comprised 9.4%, 3.6%, and 0.8% of the ticks, respectively. Among 983 pools tested, Rickettsia spp. (216 pools, 1.6% MIR) were the most prevalent pathogens across all tick species, with R. japonica and R. monacensis frequently detected in I. nipponensis and Haemaphysalis spp., respectively. Borrelia spp. (28 pools, 0.2% MIR) were predominantly detected in I. nipponensis (27 pools, 13.8% MIR, P < 0.001). Co-infections, mainly involving Rickettsia monacensis and Borrelia afzelii, were detected in I. nipponensis. Notably, this study identified R. monacensis for the first time in A. testudinarium in South Korea. These findings offer valuable insights into the tick population and associated pathogens in the region, underscoring the importance of tick-borne disease surveillance and prevention measures.
Topics: Animals; Republic of Korea; Rickettsia; Ticks; Tick-Borne Diseases; Prevalence; Borrelia; Anaplasma phagocytophilum; Ehrlichia; Coxiella burnetii; Phlebovirus
PubMed: 38811622
DOI: 10.1038/s41598-024-61126-y -
Frontiers in Cellular and Infection... 2024The mosquito-borne Rift Valley fever virus (RVFV) from the family is a single-stranded RNA virus that causes the re-emerging zoonotic disease Rift Valley fever (RVF)....
HSP90 is part of a protein complex with the L polymerase of Rift Valley fever phlebovirus and prevents its degradation by the proteasome during the viral genome replication/transcription stage.
The mosquito-borne Rift Valley fever virus (RVFV) from the family is a single-stranded RNA virus that causes the re-emerging zoonotic disease Rift Valley fever (RVF). Classified as a Category A agent by the NIH, RVFV infection can cause debilitating disease or death in humans and lead to devastating economic impacts by causing abortion storms in pregnant cattle. In a previous study, we showed that the host chaperone protein HSP90 is an RVFV-associated host factor that plays a critical role post viral entry, during the active phase of viral genome replication/transcription. In this study, we have elucidated the molecular mechanisms behind the regulatory effect of HSP90 during infection with RVFV. Our results demonstrate that during the early infection phase, host HSP90 associates with the viral RNA-dependent RNA polymerase (L protein) and prevents its degradation through the proteasome, resulting in increased viral replication.
Topics: Virus Replication; HSP90 Heat-Shock Proteins; Rift Valley fever virus; Proteasome Endopeptidase Complex; Animals; Proteolysis; Genome, Viral; Humans; RNA-Dependent RNA Polymerase; Host-Pathogen Interactions; Viral Proteins; Transcription, Genetic; Rift Valley Fever; Cell Line
PubMed: 38800833
DOI: 10.3389/fcimb.2024.1331755 -
Viruses Apr 2024This study aimed to analyze the correlation between the cycle threshold (Ct) values of severe fever with thrombocytopenia syndrome (SFTS) virus small (S) and middle (M)...
Correlation between the Cycle Threshold Values in Detection of Severe Fever with Thrombocytopenia Syndrome Virus Using PowerChek SFTSV Real-Time PCR Kit and Viral Load: Prognostic Implications.
BACKGROUND
This study aimed to analyze the correlation between the cycle threshold (Ct) values of severe fever with thrombocytopenia syndrome (SFTS) virus small (S) and middle (M) segments and the SFTS viral load, aiming to estimate the initial viral load and predict prognosis in the early clinical course.
METHOD
A retrospective study was conducted with confirmed SFTS patients at Jeju National University Hospital (2016-2022). Patients were categorized into non-fatal and fatal groups.
RESULTS
This study included 49 patients with confirmed SFTS (non-fatal group, = 42; fatal group, = 7). A significant negative correlation (-0.783) was observed between the log SFTS viral load and Ct values ( < 0.001). This negative correlation was notably stronger in the fatal group (correlation coefficient -0.940) than in the non-fatal group (correlation coefficient -0.345).
CONCLUSION
In this study, we established a correlation between SFTS viral load and Ct values for estimating the initial viral load and early predicting prognosis. These results are expected to offer valuable insights for SFTS patient treatment and prognosis prediction.
Topics: Humans; Viral Load; Phlebovirus; Severe Fever with Thrombocytopenia Syndrome; Male; Female; Prognosis; Retrospective Studies; Aged; Middle Aged; Real-Time Polymerase Chain Reaction; Aged, 80 and over; Adult; RNA, Viral
PubMed: 38793582
DOI: 10.3390/v16050700 -
Emerging Infectious Diseases Jun 2024We isolated severe fever with thrombocytopenia syndrome virus (SFTSV) from farmed minks in China, providing evidence of natural SFTSV infection in farmed minks. Our...
We isolated severe fever with thrombocytopenia syndrome virus (SFTSV) from farmed minks in China, providing evidence of natural SFTSV infection in farmed minks. Our findings support the potential role of farmed minks in maintaining SFTSV and are helpful for the development of public health interventions to reduce human infection.
Topics: Phlebovirus; China; Disease Outbreaks; Severe Fever with Thrombocytopenia Syndrome; Animals; Mink; Phylogeny; Humans; Farms
PubMed: 38781980
DOI: 10.3201/eid3006.240283 -
Antiviral Research Jul 2024The severe fever with thrombocytopenia syndrome virus (SFTSV) is a novel phlebovirus, recently being officially renamed as Dabie bandavirus, and a causative agent for an...
The severe fever with thrombocytopenia syndrome virus (SFTSV) is a novel phlebovirus, recently being officially renamed as Dabie bandavirus, and a causative agent for an emerging infectious disease associated with high fatality. Effective therapeutics and vaccines are lacking and disease pathogenesis is yet to be fully elucidated. In our effort to identify new SFTSV inhibitory molecules, 6-Thioguanine (6-TG) was found to potently inhibit SFTSV infection. 6-TG has been widely used as therapeutic agent since the approval of the Food and Drug Administration in the 1960s. In the current study, we showed that 6-TG was a potent inhibitor of SFTSV infection with 50% effective concentrations (EC) of 3.465 μM in VeroE6 cells, and 1.848 μM in HUVEC cells. The selectivity index (SI) was >57 in VeroE6 cells and >108 in HUVEC cells, respectively. The SFTSV RNA transcription, protein synthesis, and progeny virions were reduced in a dose dependent manner by the presence of 6-TG in the in vitro infection assay. Further study on the mechanism of the anti-SFTSV activity showed that 6-TG downregulated the production of early growth response gene-1 (EGR1). Using gene silencing and overexpression, we further confirmed that EGR1 was a host restriction factor against SFTSV. Meanwhile, treatment of infected experimental animals with 6-TG inhibited SFTSV infection and alleviated multi-organ dysfunction. In conclusion, we have identified 6-TG as an effective inhibitor of SFTSV replication via the inhibition of EGR1 expression. Further studies are needed to evaluate of 6-TG as a potential therapeutic for treating SFTS.
Topics: Animals; Phlebovirus; Humans; Virus Replication; Thioguanine; Human Umbilical Vein Endothelial Cells; Mice; Vero Cells; Antiviral Agents; Chlorocebus aethiops; Early Growth Response Protein 1; Severe Fever with Thrombocytopenia Syndrome; Cell Line
PubMed: 38777095
DOI: 10.1016/j.antiviral.2024.105916 -
Yi Chuan = Hereditas Nov 2023Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease, caused by severe fever with thrombocytopenia syndrome virus (SFTSV), which is...
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease, caused by severe fever with thrombocytopenia syndrome virus (SFTSV), which is primarily transmitted via tick bites. Clusters of SFTS caused by human-to-human transmission have been reported both at home and abroad, mainly focused on the transmission or exposure modes. However, the correlation between SFTS clusters and viral genotypes has not been investigated. This study mainly reported two clusters of SFTS in Xinyang City, Henan Province, from 2022 to 2023, discussed the possible route of person-to-person transmission of SFTSV infection and analyzed the association between SFTS clusters and virus genotypes. We found that two groups of SFTSV in two clusters were clustered separately into different genotypes through viral sequence analysis of 4 confirmed patients. We also performed phylogenetic analysis, after including SFTSV sequences obtained from SFTS clusters deposited in the GenBank. Three SFTSV genotypes have been reported among cases of human-to-human transmission, suggesting that the occurrence of SFTS clusters may not be related to SFTSV genotypes. This study provided genetic evidence for revealing the chain of human-to-human transmission of SFTS clusters, indicating that contact with patients' blood is an important transmission route of SFTSV. The findings laid the foundation for preventing and controlling human-to-human transmission of SFTS.
Topics: Humans; Phlebovirus; Severe Fever with Thrombocytopenia Syndrome; Phylogeny; Genotype; China; Male; Female
PubMed: 38764271
DOI: 10.16288/j.yczz.23-176 -
Diagnostic Microbiology and Infectious... Aug 2024Severe Fever with Thrombocytopenia Syndrome (SFTS) is a tick-borne disease caused by the SFTS virus (SFTSV) which has the potential to become a pandemic and is currently... (Review)
Review
The first diagnosis of Severe Fever with Thrombocytopenia Syndrome caused by tick-borne Severe Fever with Thrombocytopenia Syndrome virus in Chongqing, China: A case report and literature review.
BACKGROUND
Severe Fever with Thrombocytopenia Syndrome (SFTS) is a tick-borne disease caused by the SFTS virus (SFTSV) which has the potential to become a pandemic and is currently a major public health concern.
CASE PRESENTATION
We present the case of a 74-year-old female from an urban area of Chongqing, with leukocytopenia, thrombocytopenia, organ function, inflammatory, blood coagulation, and immune abnormalities. SFTSV infection was confirmed through molecular detection and metagenomic next-generation sequencing (mNGS) analysis, indicating a diagnosis of SFTS due to the patient's history of tick bites. The patient received symptomatic and supportive therapy, including antibiotics, antiviral treatment, and antifungal therapy, and finally discharged from the hospital on day 18.
CONCLUSIONS
This study highlights the need for increased awareness, early diagnosis, and prompt treatment for tick-borne SFTS. It also provides a comprehensive understanding of the disease's characteristics, pathogenesis, detection methods, and available treatments.
Topics: Humans; Female; Phlebovirus; Severe Fever with Thrombocytopenia Syndrome; Aged; China; High-Throughput Nucleotide Sequencing; Tick Bites; Tick-Borne Diseases; Antiviral Agents
PubMed: 38761614
DOI: 10.1016/j.diagmicrobio.2024.116350 -
Virology Journal May 2024Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease. SFTS virus (SFTSV) is transmitted by tick bites and contact with the blood or body...
BACKGROUND
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease. SFTS virus (SFTSV) is transmitted by tick bites and contact with the blood or body fluids of SFTS patients. Animal-to-human transmission of SFTS has been reported in Japan, but not in China. In this study, the possible transmission route of two patients who fed and cared for farm-raised fur animals in a mink farm was explored.
METHOD
An epidemiological investigation and a genetic analysis of patients, animals and working environment were carried out.
RESULTS
It was found that two patients had not been bitten by ticks and had no contact with patients infected with SFTS virus, but both of them had skinned the dying animals. 54.55% (12/22) of the farm workers were positive for SFTS virus antibody. By analyzing the large, medium and small segments sequences, the viral sequences from the two patients, animals and environments showed 99.9% homology.
CONCLUSION
It is suspected that the two patients may be directly infected by farm-raised animals, and that the virus may have been transmitted by aerosols when skinning dying animals. Transmission by direct blood contacts or animal bites cannot be ignored.
Topics: Animals; Humans; Antibodies, Viral; China; Farmers; Farms; Mink; Phlebovirus; Phylogeny; RNA, Viral; Severe Fever with Thrombocytopenia Syndrome
PubMed: 38760812
DOI: 10.1186/s12985-024-02387-x