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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 -
Microorganisms Dec 2023Vector-borne viral diseases (VBVDs) continue to pose a considerable public health risk to animals and humans globally. Vectors have integral roles in autochthonous... (Review)
Review
Vector-borne viral diseases (VBVDs) continue to pose a considerable public health risk to animals and humans globally. Vectors have integral roles in autochthonous circulation and dissemination of VBVDs worldwide. The interplay of agricultural activities, population expansion, urbanization, host/pathogen evolution, and climate change, all contribute to the continual flux in shaping the epidemiology of VBVDs. In recent decades, VBVDs, once endemic to particular countries, have expanded into new regions such as Iran and its neighbors, increasing the risk of outbreaks and other public health concerns. Both Iran and its neighboring countries are known to host a number of VBVDs that are endemic to these countries or newly circulating. The proximity of Iran to countries hosting regional diseases, along with increased global socioeconomic activities, e.g., international trade and travel, potentially increases the risk for introduction of new VBVDs into Iran. In this review, we examined the epidemiology of numerous VBVDs circulating in Iran, such as Chikungunya virus, Dengue virus, Sindbis virus, West Nile virus, Crimean-Congo hemorrhagic fever virus, Sandfly-borne phleboviruses, and Hantavirus, in relation to their vectors, specifically mosquitoes, ticks, sandflies, and rodents. In addition, we discussed the interplay of factors, e.g., urbanization and climate change on VBVD dissemination patterns and the consequent public health risks in Iran, highlighting the importance of a One Health approach to further surveil and to evolve mitigation strategies.
PubMed: 38138150
DOI: 10.3390/microorganisms11123006 -
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 -
Global Change Biology Dec 2023Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with increasing incidence and geographic extent. The extent to which global climate...
Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with increasing incidence and geographic extent. The extent to which global climate change affects the incidence of SFTS disease remains obscure. We use an integrated multi-model, multi-scenario framework to assess the impact of global climate change on SFTS disease in China. The spatial distribution of habitat suitability for the tick Haemaphysalis longicornis was predicted by applying a boosted regression tree model under four alternative climate change scenarios (RCP2.6, RCP4.5, RCP6.0, and RCP8.5) for the periods 2030-2039, 2050-2059, and 2080-2089. We incorporate the SFTS cases in the mainland of China from 2010 to 2019 with environmental variables and the projected distribution of H. longicornis into a generalized additive model to explore the current and future spatiotemporal dynamics of SFTS. Our results demonstrate an expanded geographic distribution of H. longicornis toward Northern and Northwestern China, showing a more pronounced change under the RCP8.5 scenario. In contrast, the environmental suitability of H. longicornis is predicted to be reduced in Central and Eastern China. The SFTS incidence in three time periods (2030-2039, 2050-2059, and 2080-2089) is predicted to be increased as compared to the 2010s in the context of various RCPs. A heterogeneous trend across provinces, however, was observed, when an increased incidence in Liaoning and Shandong provinces, while decreased incidence in Henan province is predicted. Notably, we predict possible outbreaks in Xinjiang and Yunnan in the future, where only sporadic cases have been reported previously. These findings highlight the need for tick control and population awareness of SFTS in endemic regions, and enhanced monitoring in potential risk areas.
Topics: Animals; Severe Fever with Thrombocytopenia Syndrome; Phlebovirus; China; Ecosystem; Ixodidae
PubMed: 37846616
DOI: 10.1111/gcb.16969 -
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 -
The Journal of General Virology Sep 2023The family comprises viruses with 2-8 segments of negative-sense or ambisense RNA, comprising 8.1-25.1 kb in total. Virions are typically enveloped with spherical or...
The family comprises viruses with 2-8 segments of negative-sense or ambisense RNA, comprising 8.1-25.1 kb in total. Virions are typically enveloped with spherical or pleomorphic morphology but can also be non-enveloped filaments. Phenuivirids infect animals including livestock and humans, birds, plants or fungi, as well as arthropods that serve as single hosts or act as biological vectors for transmission to animals or plants. Phenuivirids include important pathogens of humans, livestock, seafood and agricultural crops. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family , which is available at ictv.global/report/phenuiviridae.
Topics: Animals; Humans; RNA Viruses; Virion; Arthropods; RNA
PubMed: 37702592
DOI: 10.1099/jgv.0.001893 -
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