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PLoS Neglected Tropical Diseases Sep 2023Severe fever with thrombocytopenia syndrome virus (SFTSV), an etiological agent causing febrile human disease was identified as an emerging tick-borne bunyavirus. The...
Severe fever with thrombocytopenia syndrome virus (SFTSV), an etiological agent causing febrile human disease was identified as an emerging tick-borne bunyavirus. The clinical disease characteristics and case fatality rates of SFTSV may vary across distinct regions and among different variant genotypes. From 2018 to 2022, we surveyed and recruited 202 severe fever with thrombocytopenia syndrome (SFTS) patients in Hubei Province, a high-incidence area of the epidemic, and conducted timely and systematic research on the disease characteristics, SFTSV diversity, and the correlation between virus genome variation and clinical diseases. Our study identified at least 6 genotypes of SFTSV prevalent in Hubei Province based on the analysis of the S, M, and L genome sequences of 88 virus strains. Strikingly, the dominant genotype of SFTSV was found to change during the years, indicating a dynamic shift in viral genetic diversity in the region. Phylogenetic analysis revealed the genetic exchange of Hubei SFTSV strains was relatively frequent, including 3 reassortment strains and 8 recombination strains. Despite the limited sample size, SFTSV C1 genotype may be associated with higher mortality compared to the other four genotypes, and the serum amyloid A (SAA) level, an inflammatory biomarker, was significantly elevated in these patients. Overall, our data summarize the disease characteristics of SFTSV in Hubei Province, highlight the profound changes in viral genetic diversity, and indicate the need for in-depth monitoring and exploration of the relationship between viral mutations and disease severity.
Topics: Humans; Severe Fever with Thrombocytopenia Syndrome; Bunyaviridae Infections; Phylogeny; Phlebovirus; China; Genetic Variation
PubMed: 37721962
DOI: 10.1371/journal.pntd.0011654 -
International Journal of Infectious... Sep 2023Severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV) is an emerging tick-borne bunyavirus with a high pathogenicity. Little is known about the longitudinal...
OBJECTIVES
Severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV) is an emerging tick-borne bunyavirus with a high pathogenicity. Little is known about the longitudinal dynamics of the SFTSV-specific neutralizing antibody (NAb) and the related factors in patients with SFTS.
METHODS
A prospective cohort study of patients with laboratory-confirmed SFTS were conducted. Antiglomerulonephritis-immunoglobulin G (anti-Gn-IgG) and NAb titers were examined in serially collected serum samples, and their dynamic features were analyzed.
RESULTS
NAb was initially detected at 15 days after symptom onset in surviving patients with SFTS, with positive rates of 37.21% (16/43), whereas neither anti-Gn-IgG antibody nor NAb was detected in patients with fatal SFTS during their hospitalization. The NAb levels reached the peak at 2 months after symptom onset, and then gradually declined, with a rapid downward trend from 6 months to 4 years and a relatively slow downward trend from 5 to 10 years. There was a positive correlation between NAb and anti-Gn-IgG titers in surviving patients with SFTS (r = 0.699, P <0.001). Patients with a mild illness or low viral load experienced early NAb seroconversion. Six different dynamic patterns of NAb were noted in surviving patients.
CONCLUSION
These data provide useful information regarding the dynamic changes in NAb in patients with SFTS during the acute and convalescent phases and the follow-up period.
Topics: Humans; Severe Fever with Thrombocytopenia Syndrome; Antibodies, Neutralizing; Prospective Studies; Bunyaviridae Infections; Antibodies, Viral; Phlebovirus; Immunoglobulin G
PubMed: 37247691
DOI: 10.1016/j.ijid.2023.05.018 -
Frontiers in Cellular and Infection... 2023The study aimed to comprehensively describe and evaluate the pathogenic and clinical characteristics of severe fever with thrombocytopenia syndrome (SFTS) patients with...
OBJECTIVE
The study aimed to comprehensively describe and evaluate the pathogenic and clinical characteristics of severe fever with thrombocytopenia syndrome (SFTS) patients with co-infections.
METHODS
We retrospectively collected clinical data and laboratory indicators of the SFTS patients at Tongji Hospital from October 2021 to July 2023.
RESULTS
A total of 157 patients with SFTS virus (SFTSV) infection were involved in the analysis, including 43 co-infection and 114 non-co-infection patients. The pathogens responsible for co-infection were primarily isolated from respiratory specimens. Fungal infections, primarily , were observed in 22 cases. Bacterial infections, with and carbapenem-resistant as the main pathogens, were identified in 20 cases. SFTS patients with co-infection exhibited higher mortality (=0.011) compared to non-co-infection patients. Among SFTS patients co-infected with both bacteria and fungi (8 cases) or specific drug-resistant strains (11 cases), the mortality rate was as high as 70% (14/19). In comparison with the non-co-infection group, SFTS patients with co-infection displayed significant alteration in inflammatory markers, coagulation function, and liver function indicators.
CONCLUSION
The mortality rate of SFTS patients with co-infection is relatively high, underscoring the need for enhanced monitoring and timely, appropriate treatment to minimize the mortality rate.
Topics: Humans; Severe Fever with Thrombocytopenia Syndrome; Coinfection; Retrospective Studies; Phlebovirus; Bunyaviridae Infections; Thrombocytopenia
PubMed: 38106473
DOI: 10.3389/fcimb.2023.1298050 -
PLoS Pathogens Aug 2023Toscana virus is a major cause of arboviral disease in humans in the Mediterranean basin during summer. However, early virus-host cell interactions and entry mechanisms...
Toscana virus is a major cause of arboviral disease in humans in the Mediterranean basin during summer. However, early virus-host cell interactions and entry mechanisms remain poorly characterized. Investigating iPSC-derived human neurons and cell lines, we found that virus binding to the cell surface was specific, and 50% of bound virions were endocytosed within 10 min. Virions entered Rab5a+ early endosomes and, subsequently, Rab7a+ and LAMP-1+ late endosomal compartments. Penetration required intact late endosomes and occurred within 30 min following internalization. Virus entry relied on vacuolar acidification, with an optimal pH for viral membrane fusion at pH 5.5. The pH threshold increased to 5.8 with longer pre-exposure of virions to the slightly acidic pH in early endosomes. Strikingly, the particles remained infectious after entering late endosomes with a pH below the fusion threshold. Overall, our study establishes Toscana virus as a late-penetrating virus and reveals an atypical use of vacuolar acidity by this virus to enter host cells.
Topics: Humans; Sandfly fever Naples virus; Endocytosis; Endosomes; Vacuoles; Virus Internalization; Hydrogen-Ion Concentration
PubMed: 37578957
DOI: 10.1371/journal.ppat.1011562 -
Virology Journal Sep 2023Severe fever with thrombocytopenia syndrome (SFTS) is a common tick-borne, natural focal disease. SFTS virus (SFTSV) transmission can occur between family members...
BACKGROUND
Severe fever with thrombocytopenia syndrome (SFTS) is a common tick-borne, natural focal disease. SFTS virus (SFTSV) transmission can occur between family members through close contact with an infected patient. In this study, we explored the possible transmission route of an outbreak cluster in east China.
METHOD
A case-control study was carried out to analyze the potential risk factors for person-to-person transmission. Bunia virus was detected by IgM antibody, enzyme-linked immunosorbent assay, and reverse transcription polymerase chain reaction. Chi-square, univariate, and multivariate analyses were performed to calculate the association of possible risk factors for SFTSV transmission.
RESULTS
Two patients had a clear history of blood and aerosols contact, and one may be exposed to aerosols in a closed environment. Five close contacts of the Index patient were IgM-positive and three were IgM and SFTSV RNA positive. Exposure to a poorly ventilated space where the corpse was stored (χ = 5.49, P = 0.019) and contact with the Index patient's contaminated items (χ = 15.77, P < 0.001) significantly associated with SFTSV infection.
CONCLUSION
We suspect that the cluster outbreak was possibly a person-to-person transmission of SFTSV, which may have been transmitted by directly contacting with blood of SFTS patient. The propagation of aerosols in closed environments is also an undeniable transmission.
Topics: Humans; Severe Fever with Thrombocytopenia Syndrome; Case-Control Studies; China; Immunoglobulin M
PubMed: 37658435
DOI: 10.1186/s12985-023-02155-3 -
Journal of Comparative Pathology Feb 2024Phlebotomine sand flies (Diptera: Phlebotominae) are vectors of human and animal pathogens, including Leishmania species protozoan parasites and viruses of the genus... (Review)
Review
Phlebotomine sand flies (Diptera: Phlebotominae) are vectors of human and animal pathogens, including Leishmania species protozoan parasites and viruses of the genus Phlebovirus. In Europe, visceral zoonotic leishmaniasis caused by Leishmania infantum, a deadly disease when left untreated, is endemic in southern countries, and dogs are the main reservoir hosts for human infection. Most phleboviruses cause asymptomatic infections or flu-like syndromes in humans, but Toscana phlebovirus can cause meningitis and encephalitis. These diseases are likely to re-emerge, posing a growing threat to public and animal health. Potential triggers include the movement of humans and dogs, increasing numbers of immunosuppressive conditions, climate change and other human-mediated environmental changes. An overview of the main epidemiological characteristics of the pathogens transmitted by sand flies in Europe and the potential triggers involved in their emergence and re-emergence are reviewed here. There is a need to implement mandatory notification of human and canine leishmaniases and human phleboviruses and coordinated epidemiological surveillance programmes at a European level, and to raise awareness among healthcare professionals and citizens about sand fly-borne diseases, following a One Health approach.
Topics: Animals; Dogs; Humans; Psychodidae; Europe; Leishmaniasis, Visceral; Encephalitis; Leishmania infantum; Dog Diseases
PubMed: 38320331
DOI: 10.1016/j.jcpa.2024.01.001 -
Protein & Cell Dec 2023
Topics: Humans; Severe Fever with Thrombocytopenia Syndrome; Phlebovirus
PubMed: 37038326
DOI: 10.1093/procel/pwad019 -
Nature Communications Jul 2023Rift Valley fever virus (RVFV) is an emerging mosquito-transmitted virus that circulates in livestock and humans in Africa and the Middle East. Outbreaks lead to high...
Rift Valley fever virus (RVFV) is an emerging mosquito-transmitted virus that circulates in livestock and humans in Africa and the Middle East. Outbreaks lead to high rates of miscarriages in domesticated livestock. Women are also at risk of vertical virus transmission and late-term miscarriages. MAb RVFV-268 is a highly potent recombinant neutralizing human monoclonal antibody that targets RVFV. Here we show that mAb RVFV-268 reduces viral replication in rat placenta explant cultures and prevents vertical transmission in a rat model of congenital RVF. Passive transfer of mAb RVFV-268 from mother to fetus occurs as early as 6 h after administration and persists through 24 h. Administering mAb RVFV-268 2 h prior to RVFV challenge or 24 h post-challenge protects the dams and offspring from RVFV infection. These findings support mAb RVFV-268 as a pre- and post-infection treatment to subvert RVFV infection and vertical transmission, thus protecting the mother and offspring.
Topics: Pregnancy; Animals; Humans; Rats; Female; Rift Valley fever virus; Antibodies, Neutralizing; Rift Valley Fever; Abortion, Spontaneous; Antibodies, Viral; Livestock
PubMed: 37495594
DOI: 10.1038/s41467-023-40187-z -
Viruses Dec 2023Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne zoonotic disease caused by the SFTS virus (SFTSV). In Thailand, three human cases of SFTS...
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne zoonotic disease caused by the SFTS virus (SFTSV). In Thailand, three human cases of SFTS were reported in 2019 and 2020, but there was no report of SFTSV infection in animals. Our study revealed that at least 16.6% of dogs in Thailand were seropositive for SFTSV infection, and the SFTSV-positive dogs were found in several districts in Thailand. Additionally, more than 70% of the serum samples collected at one shelter possessed virus-neutralization antibodies against SFTSV and the near-complete genome sequences of the SFTSV were determined from one dog in the shelter. The dog SFTSV was genetically close to those from Thailand and Chinese patients and belonged to genotype J3. These results indicated that SFTSV has already spread among animals in Thailand.
Topics: Animals; Humans; Dogs; Severe Fever with Thrombocytopenia Syndrome; Bunyaviridae Infections; Seroepidemiologic Studies; Thailand; Antibodies, Viral; Phlebovirus; Tick-Borne Diseases
PubMed: 38140644
DOI: 10.3390/v15122403 -
BioRxiv : the Preprint Server For... Sep 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...
BACKGROUND
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.
METHODOLOGY
To identify the host factors or genes essential for RVFV replication, we conducted a CRISPR-Cas9 knock-out screen in human A549 cells. We then validated the putative genes using siRNA-mediated knockdowns and CRISPR-Cas9-mediated knockout studies, respectively. The role of a candidate gene in the virus replication cycle was assessed by measuring intracellular viral RNA accumulation, and the virus titers by plaque assay or TCID assay.
FINDINGS
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 knockdowns found that silencing two genes (WDR7 and LRP1) significantly impaired RVFV replication. For further analysis, we focused on the gene since the role of in RVFV replication was previously described in detail. Knock-out A549 cell lines were generated and used to dissect the effect of on RVFV and another bunyavirus, La Crosse encephalitis virus (LACV). We observed significant effects of knock-out 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 (24h) when compared to LACV which was affected an earlier replication phase (12h).
CONCLUSION
In summary, we have identified as an essential host factor for the replication of two relevant bunyaviruses, RVFV and LACV. Future studies will investigate the mechanistic role by which facilitates Phlebovirus replication.
PubMed: 37808812
DOI: 10.1101/2023.09.28.559935