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Journal of Virology Jun 2023Rift Valley fever virus (RVFV) (family ) can cause severe disease, and outbreaks of this mosquito-borne pathogen pose a significant threat to public and animal health....
Rift Valley fever virus (RVFV) (family ) can cause severe disease, and outbreaks of this mosquito-borne pathogen pose a significant threat to public and animal health. Yet many molecular aspects of RVFV pathogenesis remain incompletely understood. Natural RVFV infections are acute, characterized by a rapid onset of peak viremia during the first days post-infection, followed by a rapid decline. Although studies identified a major role of interferon (IFN) responses in counteracting the infection, a comprehensive overview of the specific host factors that play a role in RVFV pathogenesis is still lacking. Here, the host transcriptional profiles in the liver and spleen tissues of lambs exposed to RVFV are studied using RNA sequencing (RNA-seq) technology. We validate that IFN-mediated pathways are robustly activated in response to infection. We also link the observed hepatocellular necrosis with severely compromised organ function, which is reflected as a marked downregulation of multiple metabolic enzymes essential for homeostasis. Furthermore, we associate the elevated basal expression of in the liver with RVFV tissue tropism. Collectively, the results of this study deepen the knowledge of the host response during RVFV infection and reveal new insights into the gene regulation networks underlying pathogenesis in a natural host. Rift Valley fever virus (RVFV) is a mosquito-transmitted pathogen capable of causing severe disease in animals and humans. Outbreaks of RVFV pose a significant threat to public health and can result in substantial economic losses. Little is known about the molecular basis of RVFV pathogenesis , particularly in its natural hosts. We employed RNA-seq technology to investigate genome-wide host responses in the liver and spleen of lambs during acute RVFV infection. We show that RVFV infection drastically decreases the expression of metabolic enzymes, which impairs normal liver function. Moreover, we highlight that basal expression levels of the host factor may be a determinant of RVFV tissue tropism. This study links the typical pathological phenotype induced by RVFV infection with tissue-specific gene expression profiles, thereby improving our understanding of RVFV pathogenesis.
Topics: Animals; Homeostasis; Rift Valley Fever; Rift Valley fever virus; Sheep; Transcriptome; Low Density Lipoprotein Receptor-Related Protein-1; Liver; Host-Pathogen Interactions; Interferons
PubMed: 37306574
DOI: 10.1128/jvi.00415-23 -
Viruses Nov 2023Mudanjiang phlebovirus (MJPV) is a newly discovered phlebovirus, initially detected from ticks in China in 2022. In this study, by next-generation sequencing (NGS) on a...
Mudanjiang phlebovirus (MJPV) is a newly discovered phlebovirus, initially detected from ticks in China in 2022. In this study, by next-generation sequencing (NGS) on a wide variety of ticks and wild small animals in China, we detected MJPV from and . Additionally, we conducted RT-PCR and sequencing on 1815 adult ticks and 805 wild small mammals collected from eight provinces in China between 2017 and 2021. MJPV RNA-positive results were found in 0.22% (4/1815) of tick samples, as well as in 0.12% (1/805) of rodent samples. All positive detections were obtained from Heilongjiang and Inner Mongolia. Sequencing analysis revealed nucleotide similarities ranging from 98.23% to 99.11%, as well as amino acid similarities ranging from 99.12% to100%, between the current MJPV strain and previously reported strains of MJPV. Phylogenetic tree analysis demonstrated that the previously reported MJPV strain along with our two variants clustered together with other tick-borne phenuiviruses, indicating their close relationship within this viral group. This study represents the first detection of MJPV infection in wild rodents, expanding the known host range for this virus in the endemic regions.
Topics: Animals; Phlebovirus; Phylogeny; Ixodes; Animals, Wild; Viruses; Rodentia; China
PubMed: 38140594
DOI: 10.3390/v15122353 -
The Journal of Veterinary Medical... Feb 2024Severe fever with thrombocytopenia syndrome (SFTS) is an infectious disease caused by a tick-borne virus called severe fever with thrombocytopenia syndrome virus...
Severe fever with thrombocytopenia syndrome (SFTS) is an infectious disease caused by a tick-borne virus called severe fever with thrombocytopenia syndrome virus (SFTSV). In recent years, human infections through contact with ticks and through contact with the bodily fluids of infected dogs and cats have been reported; however, no vaccine is currently available. SFTSV has two glycoproteins (Gn and Gc) on its envelope, which are vaccine-target antigens involved in immunogenicity. In the present study, we constructed novel SFTS vaccine candidates using an adeno-associated virus (AAV) vector to transport the SFTSV glycoprotein genome. AAV vectors are widely used in gene therapy and their safety has been confirmed in clinical trials. Recently, AAV vectors have been used to develop influenza and SARS-CoV-2 vaccines. Two types of vaccines (AAV9-SFTSV Gn and AAV9-SFTSV Gc) carrying SFTSV Gn and Gc genes were produced. The expression of Gn and Gc proteins in HEK293T cells was confirmed by infection with vaccines. These vaccines were inoculated into mice, and the collected sera produced anti-SFTS antibodies. Furthermore, sera from AAV9-SFTSV Gn infected mice showed a potent neutralizing ability, similar to previously reported SFTS vaccine candidates that protected animals from SFTSV infection. These findings suggest that this vaccine is a promising candidate for a new SFTS vaccine.
Topics: Animals; Humans; Cats; Mice; Dogs; Severe Fever with Thrombocytopenia Syndrome; Dependovirus; Phlebovirus; Bunyaviridae Infections; COVID-19 Vaccines; Cat Diseases; HEK293 Cells; Dog Diseases; Glycoproteins; Thrombocytopenia; Rodent Diseases
PubMed: 38143087
DOI: 10.1292/jvms.23-0375 -
Emerging Microbes & Infections Dec 2023Rift Valley fever (RVF) is an arboviral disease of zoonotic origin that causes recurrent epidemics in Africa, the Arabic Peninsula, and islands of the South West of the...
Rift Valley fever (RVF) is an arboviral disease of zoonotic origin that causes recurrent epidemics in Africa, the Arabic Peninsula, and islands of the South West of the Indian Ocean. RVF occurs mainly in livestock but also affects humans with severe clinical manifestations, including neurological disorders. However, human neuropathogenesis of Rift Valley fever virus (RVFV) is still poorly characterized. To study the interactions between RVFV and the central nervous system (CNS), we focused on RVFV infection of astrocytes, the major glial cells of the CNS that have several supporting roles including immune response regulation. We confirmed the permissiveness of astrocytes to RVFV infection and highlighted a strain-dependent infectivity. We showed that RVFV infection of astrocytes induced cell apoptosis and observed that the RVFV Non-Structural protein NSs, a known virulence factor, potentially delayed apoptosis by sequestrating activated-caspase 3 in the nucleus. Our study also showed that RVFV-infected astrocytes upregulated expression of genes associated with inflammatory and type I interferon responses at the mRNA level, but not at the protein level. This inhibition of immune response is potentially due to a NSs-dependent mechanism of mRNA nuclear export inhibition. Together, these results highlighted the direct impact of RVFV infection on the human CNS through the induction of apoptosis and a possible inhibition of early-onset immune responses that are crucial for the host survival.
Topics: Animals; Humans; Rift Valley fever virus; Astrocytes; Rift Valley Fever; Immunity; RNA, Messenger
PubMed: 37306630
DOI: 10.1080/22221751.2023.2207672 -
The Journal of Infectious Diseases Dec 2023Severe fever with thrombocytopenia syndrome (SFTS) virus was first isolated in China in 2009 and has since spread to several Asian countries. SFTS is closely related to... (Observational Study)
Observational Study
BACKGROUND
Severe fever with thrombocytopenia syndrome (SFTS) virus was first isolated in China in 2009 and has since spread to several Asian countries. SFTS is closely related to environmental factors that accelerate vector growth. We evaluated the associations of SFTS and deforestation with environmental variables.
METHODS
For this observational study, we generated multiple Poisson models using national SFTS outbreak data (2013-2018) and official environmental data for Korea. We included established risk factors as variables. Deforestation was used as the main variable. All variables were analyzed according to their spatial characteristics using the R-INLA package.
RESULTS
SFTS cases increased over time and peaked in 2017, at 272, followed by a decrease in 2018. Disease mapping showed a high incidence of SFTS nationwide, with particular risks in Gangwon and Gyeonggi Provinces in the north, and Jeju in the south of South Korea. Deforestation was significantly associated with a higher risk of SFTS in the final model (relative risk, 1.751 [95% confidence interval, 1.125-2.743]).
CONCLUSIONS
SFTS outbreaks are associated with deforestation. Therefore, deforestation in Gyeonggi, Gangwon, and Jeju provinces of South Korea needs to be considered in vector-control strategies and active surveillance of SFTS occurrence.
Topics: Humans; Severe Fever with Thrombocytopenia Syndrome; Bunyaviridae Infections; Conservation of Natural Resources; Phlebovirus; China
PubMed: 37265042
DOI: 10.1093/infdis/jiad196 -
Euro Surveillance : Bulletin Europeen... Nov 2023BackgroundVarious pathogens, including bacteria, fungi, parasites, and viruses can lead to meningitis. Among viruses causing meningitis, Toscana virus (TOSV), a... (Observational Study)
Observational Study
BackgroundVarious pathogens, including bacteria, fungi, parasites, and viruses can lead to meningitis. Among viruses causing meningitis, Toscana virus (TOSV), a phlebovirus, is transmitted through sandfly bites. TOSV infection may be suspected if patients with enterovirus- and herpesvirus-negative aseptic (non-bacterial) meningitis recall recent insect bites. Other epidemiological factors (season, rural area) may be considered. The broad range of possible meningitis aetiologies poses considerable diagnosis challenges. Untargeted metagenomic next-generation sequencing (mNGS) can potentially identify pathogens, which are not considered or detected in routine diagnostic panels.AimIn this retrospective, single-centre observational study, we investigated mNGS usefulness to understand the cause of meningitis when conventional approaches fail.MethodsCerebrospinal fluid (CSF) samples from patients hospitalised in southern Spain in 2015-2019 with aseptic meningitis and no aetiology found by conventional testing, were subjected to mNGS. Patients' demographic characteristics had been recorded and physicians had asked them about recent insect bites. Obtained viral genome sequences were phylogenetically analysed.ResultsAmong 23 idiopathic cases, TOSV was identified in eight (all male; median age: 39 years, range: 15-78 years). Five cases lived in an urban setting, three occurred in autumn and only one recalled insect bites. Phylogenetic analysis of TOSV segment sequences supported one intra-genotype reassortment event.ConclusionsOur study highlights the usefulness of mNGS for identifying viral pathogens directly in CSF. In southern Spain, TOSV should be considered regardless of recalling of insect bites or other epidemiological criteria. Detection of a disease-associated reassortant TOSV emphasises the importance of monitoring the spread and evolution of phleboviruses in Mediterranean countries.
Topics: Humans; Male; Adult; Sandfly fever Naples virus; Insect Bites and Stings; Phylogeny; Retrospective Studies; Spain; Meningitis
PubMed: 37943504
DOI: 10.2807/1560-7917.ES.2023.28.45.2200913 -
Viruses Sep 2023The non-structural protein (NSs) and nucleoprotein (NP) of the severe fever with thrombocytopenia syndrome virus (SFTSV) encoded by the S segment are crucial for viral...
Non-Structural Protein-W61 as a Novel Target in Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV): An In-Vitro and In-Silico Study on Protein-Protein Interactions with Nucleoprotein and Viral Replication.
The non-structural protein (NSs) and nucleoprotein (NP) of the severe fever with thrombocytopenia syndrome virus (SFTSV) encoded by the S segment are crucial for viral pathogenesis. They reside in viroplasm-like structures (VLS), but their interaction and their significance in viral propagation remain unclear. Here, we investigated the significance of the association between NSs and NP during viral infection through in-silico and in-vitro analyses. Through in-silico analysis, three possible binding sites were predicted, at positions C6S (Cystein at 6th position to Serine), W61Y (Tryptophan 61st to Tyrosine), and S207T (Serine 207th to Threonine), three mutants of NSs were developed by site-directed mutagenesis and tested for NP interaction by co-immunoprecipitation. NSsW61Y failed to interact with the nucleoprotein, which was substantiated by the conformational changes observed in the structural analyses. Additionally, molecular docking analysis corroborated that the NSW61Y mutant protein does not interact well compared to wild-type NSs. Over-expression of wild-type NSs in HeLa cells increased the SFTSV replication by five folds, but NSsW61Y exhibited 1.9-folds less viral replication than wild-type. We demonstrated that the W61Y alteration was implicated in the reduction of NSs-NP interaction and viral replication. Thus, the present study identified a critical NSs site, which could be targeted for development of therapeutic regimens against SFTSV.
Topics: Humans; Severe Fever with Thrombocytopenia Syndrome; Nucleoproteins; HeLa Cells; Signal Transduction; Molecular Docking Simulation; Bunyaviridae Infections; Phlebovirus; Virus Replication; Serine; Viral Nonstructural Proteins
PubMed: 37766369
DOI: 10.3390/v15091963 -
Viruses Oct 2023Fermo virus is a that is increasingly reported in sand flies from northern Italy. The natural cycle is not fully understood, but the virus has been detected by direct...
Fermo virus is a that is increasingly reported in sand flies from northern Italy. The natural cycle is not fully understood, but the virus has been detected by direct methods only in sand flies. Although there is serological evidence that it can infect vertebrates, the virus has not been directly detected in animals or humans. Here, we have developed and reported a specific real-time PCR for Fermo virus. The availability of the described method will be useful to characterize the epidemiology of the FERV, ensuring, compared to previously available protocols, a more sensitive detection in insects and the possible detection in vertebrates to evaluate the presence of reservoirs and the pathogenic potential of the virus in humans or animals.
Topics: Animals; Humans; Phlebovirus; Real-Time Polymerase Chain Reaction; Psychodidae; Italy
PubMed: 37896859
DOI: 10.3390/v15102082 -
Viruses Sep 2023Sandfly-borne phleboviruses are endemic in countries around the Mediterranean Basin and pose a significant health threat for populations, with symptoms spanning from...
Sandfly-borne phleboviruses are endemic in countries around the Mediterranean Basin and pose a significant health threat for populations, with symptoms spanning from febrile diseases to central nervous system involvement. We carried out a comprehensive cross-sectional screening via microneutralization (MN) assays for a quantitative assessment of neutralizing antibodies (NAs) to seven phleboviruses representing three distinct serocomplexes, using samples previously screened via immunofluorescence assays (IFAs) in Turkey, an endemic region with various phleboviruses in circulation. We detected NAs to three phleboviruses: Toscana virus (TOSV), sandfly fever Naples virus (SFNV), and sandfly fever Sicilian virus (SFSV), while assays utilizing Adana virus, Punique virus, Massilia virus, and Zerdali virus remained negative. The most frequently observed virus exposure was due to TOSV, with a total prevalence of 22.6%, followed by SFNV (15.3%) and SFSV (12.1%). For each virus, IFA reactivity was significantly associated with NA detection, and further correlated with NA titers. TOSV and SFSV seroreactivities were co-detected, suggesting exposure to multiple pathogenic viruses presumably due to shared sandfly vectors. In 9.6% of the samples, multiple virus exposure was documented. In conclusion, our findings demonstrate widespread exposure to distinct pathogenic phleboviruses, for which diagnostic testing and serological screening efforts should be directed.
PubMed: 37766308
DOI: 10.3390/v15091902 -
Experimental Biology and Medicine... 2024Bunyamwera virus (BUNV) () has been found in Sub-Saharan Africa and demonstrated recently as cocirculating with Rift Valley Fever Virus (RVFV). Little is known regarding...
Bunyamwera virus (BUNV) () has been found in Sub-Saharan Africa and demonstrated recently as cocirculating with Rift Valley Fever Virus (RVFV). Little is known regarding the breadth of transmission modalities of Bunyamwera. Given its co-occurence with RVFV, we hypothesized the transmission system of BUNV shared similarities to the RVFV system including transmission by mosquitoes and environmentally mediated transmission through fomites and environmental contamination. We exposed mosquitoes to BUNV and evaluated their ability to transmit both vertically and horizontally. Further, we investigated the potential for a novel transmission modality via environmental contamination. We found that the LSU colony of was not competent for the virus for either horizontal or vertical transmission; but, 20% of larva exposed to virus via contaminated aquatic habitat were positive. However, transstadial clearance of the virus was absolute. Finally, under simulated temperature conditions that matched peak transmission in Rwanda, we found that BUNV was stable in both whole blood and serum for up to 28 days at higher total volume in tubes at moderate quantities (10 genome copies/mL). In addition, infectiousness of these samples was demonstrated in 80% of the replicates. At lower volume samples (in plates), infectiousness was retained out to 6-8 days with a maximum infectious titer of 10 PFU/mL. Thus, the potential for contamination of the environment and/or transmission via contaminated fomites exists. Our findings have implications for biosafety and infection control, especially in the context of food animal production.
Topics: Animals; Bunyamwera virus; Aedes; Rift Valley fever virus
PubMed: 38510492
DOI: 10.3389/ebm.2024.10114