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PloS One 2022Rift Valley fever virus (RVFV) is a veterinary and human pathogen and is an agent of bioterrorism concern. Currently, RVFV treatment is limited to supportive care, so...
Rift Valley fever virus (RVFV) is a veterinary and human pathogen and is an agent of bioterrorism concern. Currently, RVFV treatment is limited to supportive care, so new drugs to control RVFV infection are urgently needed. RVFV is a member of the order Bunyavirales, whose replication depends on the enzymatic activity of the viral L protein. Screening for RVFV inhibitors among compounds with divalent cation-coordinating motifs similar to known viral nuclease inhibitors identified 47 novel RVFV inhibitors with selective indexes from 1.1-103 and 50% effective concentrations of 1.2-56 μM in Vero cells, primarily α-Hydroxytropolones and N-Hydroxypyridinediones. Inhibitor activity and selective index was validated in the human cell line A549. To evaluate specificity, select compounds were tested against a second Bunyavirus, La Crosse Virus (LACV), and the flavivirus Zika (ZIKV). These data indicate that the α-Hydroxytropolone and N-Hydroxypyridinedione chemotypes should be investigated in the future to determine their mechanism(s) of action allowing further development as therapeutics for RVFV and LACV, and these chemotypes should be evaluated for activity against related pathogens, including Hantaan virus, severe fever with thrombocytopenia syndrome virus, Crimean-Congo hemorrhagic fever virus.
Topics: Animals; Cations, Divalent; Chlorocebus aethiops; Humans; La Crosse virus; Rift Valley fever virus; Vero Cells; Zika Virus; Zika Virus Infection
PubMed: 36112605
DOI: 10.1371/journal.pone.0274266 -
PLoS Neglected Tropical Diseases Mar 2022Rift Valley fever (RVF) is an emerging, neglected, mosquito-borne viral zoonosis associated with significant morbidity, mortality and expanding geographical scope. The... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Rift Valley fever (RVF) is an emerging, neglected, mosquito-borne viral zoonosis associated with significant morbidity, mortality and expanding geographical scope. The clinical signs and symptoms in humans are non-specific and case definitions vary. We reviewed and analysed the clinical manifestations of RVF in humans.
METHODS
In this systematic review and meta-analysis we searched on different dates, the Embase (from 1947 to 13th October 2019), Medline (1946 to 14th October 2019), Global Health (1910 to 15th October 2019), and Web of Science (1970 to 15th October 2019) databases. Studies published in English, reporting frequency of symptoms in humans, and laboratory confirmed RVF were included. Animal studies, studies among asymptomatic volunteers, and single case reports for which a proportion could not be estimated, were excluded. Quality assessment was done using a modified Hoy and Brooks et al tool, data was extracted, and pooled frequency estimates calculated using random effects meta-analysis.
RESULTS
Of the 3765 articles retrieved, less than 1% (32 articles) were included in the systematic review and meta-analysis. Nine RVF clinical syndromes were reported including the general febrile, renal, gastrointestinal, hepatic, haemorrhagic, visual, neurological, cardio-pulmonary, and obstetric syndromes. The most common clinical manifestations included fever (81%; 95% Confidence Interval (CI) 69-91; [26 studies, 1286 patients]), renal failure (41%; 23-59; [4, 327]), nausea (38%; 12-67; [6, 325]), jaundice (26%; 16-36; [15, 393]), haemorrhagic disease (26%; 17-36; [16, 277]), partial blindness (24%; 7-45; [11, 225]), encephalitis (21%; 11-33; [4, 327]), cough (4%; 0-17; [4, 11]), and miscarriage (54%) respectively. Death occurred in 21% (95% CI 14-29; [16 studies, 328 patients]) of cases, most of whom were hospitalised.
DISCUSSION
This study delineates the complex symptomatology of human RVF disease into syndromes. This approach is likely to improve case definitions and detection rates, impact outbreak control, increase public awareness about RVF, and subsequently inform 'one-health' policies. This study provides a pooled estimate of the proportion of RVF clinical manifestations alongside a narrative description of clinical syndromes. However, most studies reviewed were case series with small sample sizes and enrolled mostly in-patients and out-patients, and captured symptoms either sparsely or using broad category terms.
Topics: Animals; Disease Outbreaks; Humans; One Health; Rift Valley Fever; Rift Valley fever virus; Syndrome; Zoonoses
PubMed: 35333856
DOI: 10.1371/journal.pntd.0010233 -
Life Science Alliance Jul 2023Viruses with an RNA genome are often the cause of zoonotic infections. In order to identify novel pro-viral host cell factors, we screened a haploid...
Viruses with an RNA genome are often the cause of zoonotic infections. In order to identify novel pro-viral host cell factors, we screened a haploid insertion-mutagenized mouse embryonic cell library for clones that are resistant to Rift Valley fever virus (RVFV). This screen returned the low-density lipoprotein receptor-related protein 1 (LRP1) as a top hit, a plasma membrane protein involved in a wide variety of cell activities. Inactivation of in human cells reduced RVFV RNA levels already at the attachment and entry stages of infection. Moreover, the role of LRP1 in promoting RVFV infection was dependent on physiological levels of cholesterol and on endocytosis. In the human cell line HuH-7, LRP1 also promoted early infection stages of sandfly fever Sicilian virus and La Crosse virus, but had a minor effect on late infection by vesicular stomatitis virus, whereas encephalomyocarditis virus was entirely LRP1-independent. Moreover, siRNA experiments in human Calu-3 cells demonstrated that also SARS-CoV-2 infection benefitted from LRP1. Thus, we identified LRP1 as a host factor that supports infection by a spectrum of RNA viruses.
Topics: Animals; Humans; Mice; Low Density Lipoprotein Receptor-Related Protein-1; COVID-19; SARS-CoV-2; Rift Valley fever virus; RNA, Small Interfering; Lipoproteins, LDL
PubMed: 37072184
DOI: 10.26508/lsa.202302005 -
Emerging Infectious Diseases Dec 2021Toscana virus (TOSV) is an emerging pathogen in the Mediterranean area and is neuroinvasive in its most severe form. Basic knowledge on TOSV biology is limited. We...
Toscana virus (TOSV) is an emerging pathogen in the Mediterranean area and is neuroinvasive in its most severe form. Basic knowledge on TOSV biology is limited. We conducted a systematic review on travel-related infections to estimate the TOSV incubation period. We estimated the incubation period at 12.1 days.
Topics: Antibodies, Viral; Bunyaviridae Infections; Humans; Infectious Disease Incubation Period; Sandfly fever Naples virus; Travel; Travel-Related Illness; Virus Diseases
PubMed: 34808074
DOI: 10.3201/eid2712.203172 -
Clinical Differentiation of Severe Fever with Thrombocytopenia Syndrome from Japanese Spotted Fever.Viruses Aug 2022Severe fever with thrombocytopenia syndrome (SFTS) and Japanese spotted fever (JSF; a spotted fever group rickettsiosis) are tick-borne zoonoses that are becoming a...
Severe fever with thrombocytopenia syndrome (SFTS) and Japanese spotted fever (JSF; a spotted fever group rickettsiosis) are tick-borne zoonoses that are becoming a significant public health threat in Japan and East Asia. Strategies for treatment and infection control differ between the two; therefore, initial differential diagnosis is important. We aimed to compare the clinical characteristics of SFTS and JSF based on symptomology, physical examination, laboratory data, and radiography findings at admission. This retrospective study included patients with SFTS and JSF treated at five hospitals in Nagasaki Prefecture, western Japan, between 2013 and 2020. Data from 23 patients with SFTS and 38 patients with JSF were examined for differentiating factors and were divided by 7:3 into a training cohort and a validation cohort. Decision tree analysis revealed leukopenia (white blood cell [WBC] < 4000/μL) and altered mental status as the best differentiating factors (AUC 1.000) with 100% sensitivity and 100% specificity. Using only physical examination factors, absence of skin rash and altered mental status resulted in the best differentiating factors with AUC 0.871, 71.4% sensitivity, and 90.0% specificity. When treating patients with suspected tick-borne infection, WBC < 4000/µL, absence of skin rash, and altered mental status are very useful to differentiate SFTS from JSF.
Topics: Animals; Exanthema; Humans; Japan; Leukopenia; Phlebovirus; Retrospective Studies; Severe Fever with Thrombocytopenia Syndrome; Spotted Fever Group Rickettsiosis
PubMed: 36016429
DOI: 10.3390/v14081807 -
Clinical Microbiology and Infection :... Aug 2020Toscana virus is an arbovirus transmitted by sand flies within the Mediterranean area where it can cause febrile illness and neuroinvasive infections during the seasonal... (Review)
Review
BACKGROUND
Toscana virus is an arbovirus transmitted by sand flies within the Mediterranean area where it can cause febrile illness and neuroinvasive infections during the seasonal circulation period of the vector. Although it is an important cause of meningitis and encephalitis, it remains a neglected virus with limited published data, as demonstrated by <250 peer-reviewed articles since the 1970s.
OBJECTIVE
The last review article on Toscana virus was published in 2012. The aim was to compile peer-reviewed articles to provide an updated review highlighting recent findings to complement previous review articles.
SOURCES
PubMed database was searched using the 'Toscana virus' keyword from 2010 to present. A total of 152 articles were retrieved and identified studies were assessed for novel information on virus genetics, and geographic and medical aspects compared with existing knowledge reported in previous review articles.
CONTENT
Studies addressing medical, veterinary and entomological aspects have provided evidence that Toscana virus is present in North Africa, in the Balkan Peninsula, and in most of the Mediterranean islands. Besides the two previously recognized genetic lineages, a novel evolutionary lineage has been identified in the Balkan Peninsula. Co-circulation of two genetic lineages has been demonstrated in France, in Turkey and in Croatia. In addition to meningitis and meningo-encephalitis, which have been reported for 40 years, various neuroinvasive forms have been recently reported such as Guillain-Barré syndrome, hydrocephalus, myositis, fasciitis, polymyeloradiculopathy, deafness and facial paralysis.
IMPLICATION
Because it is endemic in countries bordering the Mediterranean, physicians should include Toscana virus in the differential diagnosis of patients presenting with febrile illness and/or neurological manifestations.
Topics: Africa, Northern; Animals; Balkan Peninsula; Bunyaviridae Infections; Diagnosis, Differential; Endemic Diseases; Humans; Insect Vectors; Mediterranean Region; Phylogeography; Psychodidae; Sandfly fever Naples virus
PubMed: 31904562
DOI: 10.1016/j.cmi.2019.12.015 -
Microbiome Feb 2024Haemaphysalis longicornis is drawing attentions for its geographic invasion, extending population, and emerging disease threat. However, there are still substantial gaps...
BACKGROUND
Haemaphysalis longicornis is drawing attentions for its geographic invasion, extending population, and emerging disease threat. However, there are still substantial gaps in our knowledge of viral composition in relation to genetic diversity of H. longicornis and ecological factors, which are important for us to understand interactions between virus and vector, as well as between vector and ecological elements.
RESULTS
We conducted the meta-transcriptomic sequencing of 136 pools of H. longicornis and identified 508 RNA viruses of 48 viral species, 22 of which have never been reported. Phylogenetic analysis of mitochondrion sequences divided the ticks into two genetic clades, each of which was geographically clustered and significantly associated with ecological factors, including altitude, precipitation, and normalized difference vegetation index. The two clades showed significant difference in virome diversity and shared about one fifth number of viral species that might have evolved to "generalists." Notably, Bandavirus dabieense, the pathogen of severe fever with thrombocytopenia syndrome was only detected in ticks of clade 1, and half number of clade 2-specific viruses were aquatic-animal-associated.
CONCLUSIONS
These findings highlight that the virome diversity is shaped by internal genetic evolution and external ecological landscape of H. longicornis and provide the new foundation for promoting the studies on virus-vector-ecology interaction and eventually for evaluating the risk of H. longicornis for transmitting the viruses to humans and animals. Video Abstract.
Topics: Animals; Humans; Ixodidae; Haemaphysalis longicornis; Virome; Phylogeny; Phlebovirus; Ticks
PubMed: 38378577
DOI: 10.1186/s40168-024-01753-9 -
Journal of Medical Virology Aug 2021Severe fever with thrombocytopenia syndrome (SFTS) is recognized as an emerging infectious disease. This study aimed to investigate the pathogenic mechanism of SFTS. A...
Severe fever with thrombocytopenia syndrome (SFTS) is recognized as an emerging infectious disease. This study aimed to investigate the pathogenic mechanism of SFTS. A total of 100 subjects were randomly included in the study. Cytokine levels were detected by enzyme-linked immunosorbent assay and the viral load was detected by micro drop digital PCR. The results showed that levels of interleukin-6 (IL-6), IL-8, IL-10, IFN-inducible protein-10 (IP-10), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α), transforming growth factor-β1 (TGF-β1), and regulated upon activation normal T cell expressed and secreted factor (RANTES) differed significantly among the SFTS patient group, healthy people group, and asymptomatic infection group (p < .05). Compared to the healthy people group, the patient group had increased cytokine levels (IL-6, IL-10, IP-10, MCP-1, and IFN-γ) but reduced levels of IL-8, TGF-β1, and RANTES (p < .0167). IL-6, IL-8, IL-10, IP-10, MCP-1, MIP-1α, TGF-β1, and the RANTES levels had different trends after the onset of the disease. IL-6, IL-10, IP-10, and MCP-1 levels in severe patients were higher than those in mild patients (p < .05). There was a positive correlation between viral load and IL-6 and IP-10 but a negative correlation between viral load and RANTES. SFTSV could cause a cytokine change: the cytokine levels of patients had different degrees of fluctuation after the onset of the disease. The levels of IL-6 and IL-8 in the asymptomatic infection group were found between the SFTS patients group and the healthy people group. The levels of IL-6, IL-10, IP-10, and MCP-1 in the serum could reflect the severity of the disease, and the levels of IL-6, IP-10, and RANTES were correlated with the viral load.
Topics: Aged; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Humans; Male; Middle Aged; Phlebovirus; Severe Fever with Thrombocytopenia Syndrome; Severity of Illness Index; Viral Load
PubMed: 33590892
DOI: 10.1002/jmv.26877 -
Parasites & Vectors Aug 2019Phleboviruses are mainly transmitted by sand flies and infections can result in various symptoms, including meningitis and meningoencephalitis. In endemic regions,...
BACKGROUND
Phleboviruses are mainly transmitted by sand flies and infections can result in various symptoms, including meningitis and meningoencephalitis. In endemic regions, seroprevalences in humans and animals are high. Military personnel on missions in endemic areas are at increased risk of infection, however, for soldiers from central European countries, data are scarce. The aims of this study were to determine the exposure to phleboviruses of Austrian soldiers returning from missions abroad and to assess potential risk factors. A retrospective serological study was performed with sera of 753 healthy Austrian soldiers returning from missions in Bosnia and Herzegovina (BIH, n = 61), Kosovo (n = 261), Syria (n = 101) and Lebanon (n = 63) and of soldiers prior to their missions (n = 267).
RESULTS
Altogether, 119 sera (15.8%, 119/753) were positive for anti-Phlebovirus IgG antibodies, with highest seroprevalences found in soldiers returning from Kosovo (20.69%, 54/261), followed by Syria (17.82%, 18/101), Lebanon (14.29%, 9/63) and BIH (11.48%, 7/61). Of the soldiers tested prior to their missions 11.61% (31/267) were positive. Of the 119 seropositive individuals, 30 (25.2%, 30/119) also had anti-Phlebovirus IgM antibodies. Phlebovirus seropositivity significantly correlated with symptoms of febrile illness during the respective mission (OR: 1.9, 95% CI: 1.1-3.4, P = 0.03) and with Leishmania seropositivity (OR: 2.7, 95% CI: 1.2-5.8, P = 0.009). Also, the outdoor activity "running" during the mission showed a strong trend towards an association with Phlebovirus seropositivity (OR: 1.9, 95% CI: 0.9-4.4, P = 0.08), and seropositivity generally increased with the duration of a mission (OR: 2.5, 95% CI: 0.9-7.5, P = 0.07).
CONCLUSIONS
This study indicates that soldiers are exposed to sand flies and at significant risk for Phlebovirus infection during missions in the Mediterranean area and the Middle East. Adequate prevention measures should be applied particularly during vespertine outdoor activities.
Topics: Adolescent; Adult; Animals; Antibodies, Viral; Austria; Bosnia and Herzegovina; Bunyaviridae Infections; Endemic Diseases; Female; Humans; Immunoglobulin G; Insect Vectors; Male; Middle Aged; Middle East; Military Personnel; Phlebovirus; Psychodidae; Retrospective Studies; Risk Factors; Seroepidemiologic Studies; Young Adult
PubMed: 31445517
DOI: 10.1186/s13071-019-3674-6 -
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