immunogeno: protective mechanism for rift valley fever in the democratic republic of congo.rift valley fever (rvf) is an acute, fever causing viral disease that affects domestic animals and humans. in democratic republic of congo (drc), this pathology is not well documented. no epidemic of the rvf has not been reported but sera samples collected in six provinces surveyed from 2005 to 2006 revealed 14% of apparent prevalence and, high apparent prevalence (20%) of antibodies against rvf virus was reported in katanga province during the same survey; this serological evidence was associat ...201223327406
interferon-inducible cholesterol-25-hydroxylase broadly inhibits viral entry by production of 25-hydroxycholesterol.interferons (ifn) are essential antiviral cytokines that establish the cellular antiviral state through upregulation of hundreds of interferon-stimulated genes (isgs), most of which have uncharacterized functions and mechanisms. we identified cholesterol-25-hydroxylase (ch25h) as a broadly antiviral isg. ch25h converts cholesterol to a soluble antiviral factor, 25-hydroxycholesterol (25hc). 25hc treatment in cultured cells broadly inhibited growth of enveloped viruses including vsv, hsv, hiv, an ...201223273844
the use of nanotrap particles in the enhanced detection of rift valley fever virus nucleoprotein.rift valley fever virus (rvfv) is a highly pathogenic arthropod-borne virus that has a detrimental effect on both livestock and human populations. while there are several diagnostic methodologies available for rvfv detection, many are not sensitive enough to diagnose early infections. furthermore, detection may be hindered by high abundant proteins such as albumin. previous findings have shown that nanotrap particles can be used to significantly enhance detection of various small analytes of low ...201526020252
assessing the mandatory bovine abortion notification system in france using unilist capture-recapture approach.the mandatory bovine abortion notification system in france aims to detect as soon as possible any resurgence of bovine brucellosis. however, under-reporting seems to be a major limitation of this system. we used a unilist capture-recapture approach to assess the sensitivity, i.e. the proportion of farmers who reported at least one abortion among those who detected such events, and representativeness of the system during 2006-2011. we implemented a zero-inflated poisson model to estimate the pro ...201323691004
serosurvey for zoonotic viral and bacterial pathogens among slaughtered livestock in egypt.zoonotic diseases are an important cause of human morbidity and mortality. animal populations at locations with high risk of transmission of zoonotic pathogens offer an opportunity to study viral and bacterial pathogens of veterinary and public health concern.201425198525
development of a panel of recombinase polymerase amplification assays for detection of biothreat agents.syndromic panels for infectious disease have been suggested to be of value in point-of-care diagnostics for developing countries and for biodefense. to test the performance of isothermal recombinase polymerase amplification (rpa) assays, we developed a panel of 10 rpas for biothreat agents. the panel included rpas for francisella tularensis, yersinia pestis, bacillus anthracis, variola virus, and reverse transcriptase rpa (rt-rpa) assays for rift valley fever virus, ebola virus, sudan virus, and ...201323345286
differences in aerosolization of rift valley fever virus resulting from choice of inhalation exposure chamber: implications for animal challenge studies.the aerosol characteristics of rift valley fever virus (rvfv) were evaluated to achieve reproducible infection of experimental animals with aerosolized rvfv suitable for animal efficacy studies. spray factor (sf), the ratio between the concentrations of the aerosolized agent to the agent in the aerosol generator, is used to compare performance differences between aerosol exposures. sf indicates the efficiency of the aerosolization process; a higher sf means a lower nebulizer concentration is nee ...201424532259
repurposing fda-approved drugs as therapeutics to treat rift valley fever virus infection.there are currently no fda-approved therapeutics available to treat rift valley fever virus (rvfv) infection. in an effort to repurpose drugs for rvfv treatment, a library of fda-approved drugs was screened to determine their ability to inhibit rvfv. several drugs from varying compound classes, including inhibitors of growth factor receptors, microtubule assembly/disassembly, and dna synthesis, were found to reduce rvfv replication. the hepatocellular and renal cell carcinoma drug, sorafenib, wa ...201526217313
multiplex degenerate primer design for targeted whole genome amplification of many viral genomes.background. targeted enrichment improves coverage of highly mutable viruses at low concentration in complex samples. degenerate primers that anneal to conserved regions can facilitate amplification of divergent, low concentration variants, even when the strain present is unknown. results. a tool for designing multiplex sets of degenerate sequencing primers to tile overlapping amplicons across multiple whole genomes is described. the new script, run_tiled_primers, is part of the primux software. ...201425157264
development of a taqman array card for acute-febrile-illness outbreak investigation and surveillance of emerging pathogens, including ebola virus.acute febrile illness (afi) is associated with substantial morbidity and mortality worldwide, yet an etiologic agent is often not identified. convalescent-phase serology is impractical, blood culture is slow, and many pathogens are fastidious or impossible to cultivate. we developed a real-time pcr-based taqman array card (tac) that can test six to eight samples within 2.5 h from sample to results and can simultaneously detect 26 afi-associated organisms, including 15 viruses (chikungunya, crime ...201526491176
enhanced arbovirus surveillance with deep sequencing: identification of novel rhabdoviruses and bunyaviruses in australian mosquitoes.viral metagenomics characterizes known and identifies unknown viruses based on sequence similarities to any previously sequenced viral genomes. a metagenomics approach was used to identify virus sequences in australian mosquitoes causing cytopathic effects in inoculated mammalian cell cultures. sequence comparisons revealed strains of liao ning virus (reovirus, seadornavirus), previously detected only in china, livestock-infecting stretch lagoon virus (reovirus, orbivirus), two novel dimarhabdov ...201324314645
serosurveillance of viral pathogens circulating in west africa.sub-saharan africa is home to a variety of pathogens, but disease surveillance and the healthcare infrastructure necessary for proper management and control are severely limited. lassa virus, the cause of lassa fever, a severe hemorrhagic fever in humans is endemic in west africa. in sierra leone at the kenema government hospital lassa diagnostic laboratory, up to 70 % of acute patient samples suspected of lassa fever test negative for lassa virus infection. this large amount of acute undiagnose ...201627716429
epithelial cell lines of the cotton rat (sigmodon hispidus) are highly susceptible in vitro models to zoonotic bunya-, rhabdo-, and flaviviruses.small mammals such as bats and rodents have been increasingly recognized as reservoirs of novel potentially zoonotic pathogens. however, few in vitro model systems to date allow assessment of zoonotic viruses in a relevant host context. the cotton rat (sigmodon hispidus) is a new world rodent species that has a long-standing history as an experimental animal model due to its unique susceptibility to human viruses. furthermore, wild cotton rats are associated with a large variety of known or pote ...201627142375
bat airway epithelial cells: a novel tool for the study of zoonotic viruses.bats have been increasingly recognized as reservoir of important zoonotic viruses. however, until now many attempts to isolate bat-borne viruses in cell culture have been unsuccessful. further, experimental studies on reservoir host species have been limited by the difficulty of rearing these species. the epithelium of the respiratory tract plays a central role during airborne transmission, as it is the first tissue encountered by viral particles. although several cell lines from bats were estab ...201424454736
modeling the distribution of the west nile and rift valley fever vector culex pipiens in arid and semi-arid regions of the middle east and north africa.the middle east north africa (mena) region is under continuous threat of the re-emergence of west nile virus (wnv) and rift valley fever virus (rvf), two pathogens transmitted by the vector species culex pipiens. predicting areas at high risk for disease transmission requires an accurate model of vector distribution, however, most cx. pipiens distribution modeling has been confined to temperate, forested habitats. modeling species distributions across a heterogeneous landscape structure requires ...201424962735
a fusion-inhibiting peptide against rift valley fever virus inhibits multiple, diverse viruses.for enveloped viruses, fusion of the viral envelope with a cellular membrane is critical for a productive infection to occur. this fusion process is mediated by at least three classes of fusion proteins (class i, ii, and iii) based on the protein sequence and structure. for rift valley fever virus (rvfv), the glycoprotein gc (class ii fusion protein) mediates this fusion event following entry into the endocytic pathway, allowing the viral genome access to the cell cytoplasm. here, we show that p ...201324069485
a mechanistic paradigm for broad-spectrum antivirals that target virus-cell fusion.lj001 is a lipophilic thiazolidine derivative that inhibits the entry of numerous enveloped viruses at non-cytotoxic concentrations (ic50 ≤ 0.5 µm), and was posited to exploit the physiological difference between static viral membranes and biogenic cellular membranes. we now report on the molecular mechanism that results in lj001's specific inhibition of virus-cell fusion. the antiviral activity of lj001 was light-dependent, required the presence of molecular oxygen, and was reversed by singlet ...201323637597
dicer-2 processes diverse viral rna species.rna silencing pathways play critical roles in gene regulation, virus infection, and transposon control. rna interference (rnai) is mediated by small interfering rnas (sirnas), which are liberated from double-stranded (ds)rna precursors by dicer and guide the rna-induced silencing complex (risc) to targets. although principles governing small rna sorting into risc have been uncovered, the spectrum of rna species that can be targeted by dicer proteins, particularly the viral rnas present during an ...201323424633
an assembly model of rift valley fever virus.rift valley fever virus (rvfv) is a bunyavirus endemic to africa and the arabian peninsula that infects humans and livestock. the virus encodes two glycoproteins, gn and gc, which represent the major structural antigens and are responsible for host cell receptor binding and fusion. both glycoproteins are organized on the virus surface as cylindrical hollow spikes that cluster into distinct capsomers with the overall assembly exhibiting an icosahedral symmetry. currently, no experimental three-di ...201222837754
amp-activated kinase restricts rift valley fever virus infection by inhibiting fatty acid synthesis.the cell intrinsic innate immune responses provide a first line of defense against viral infection, and often function by targeting cellular pathways usurped by the virus during infection. in particular, many viruses manipulate cellular lipids to form complex structures required for viral replication, many of which are dependent on de novo fatty acid synthesis. we found that the energy regulator ampk, which potently inhibits fatty acid synthesis, restricts infection of the bunyavirus, rift valle ...201222532801
structure of a phleboviral envelope glycoprotein reveals a consolidated model of membrane emergent viral pathogen termed severe fever with thrombocytopenia syndrome virus (sftsv) is responsible for thousands of clinical cases and associated fatalities in china, japan, and south korea. akin to other phleboviruses, sftsv relies on a viral glycoprotein, gc, to catalyze the merger of endosomal host and viral membranes during cell entry. here, we describe the postfusion structure of sftsv gc, revealing that the molecular transformations the phleboviral gc undergoes upon host cell entry ...201627325770
interplay between the virus and host in rift valley fever pathogenesis.rift valley fever virus (rvfv) belongs to the genus phlebovirus, family bunyaviridae, and carries single-stranded tripartite rna segments. the virus is transmitted by mosquitoes and has caused large outbreaks among ruminants and humans in sub-saharan african and middle east countries. the disease is characterized by a sudden onset of fever, headache, muscle pain, joint pain, photophobia, and weakness. in most cases, patients recover from the disease after a period of weeks, but some also develop ...201525766761
seroepidemiology of selected arboviruses in febrile patients visiting selected health facilities in the lake/river basin areas of lake baringo, lake naivasha, and tana river, kenya.arboviruses cause emerging and re-emerging infections affecting humans and animals. they are spread primarily by blood-sucking insects such as mosquitoes, ticks, midges, and sandflies. changes in climate, ecology, demographic, land-use patterns, and increasing global travel have been linked to an upsurge in arboviral disease. outbreaks occur periodically followed by persistent low-level circulation.025700043
undiagnosed acute viral febrile illnesses, sierra leone.sierra leone in west africa is in a lassa fever-hyperendemic region that also includes guinea and liberia. each year, suspected lassa fever cases result in submission of ≈500-700 samples to the kenema government hospital lassa diagnostic laboratory in eastern sierra leone. generally only 30%-40% of samples tested are positive for lassa virus (lasv) antigen and/or lasv-specific igm; thus, 60%-70% of these patients have acute diseases of unknown origin. to investigate what other arthropod-borne an ...024959946
a genome-wide rnai screen reveals that mrna decapping restricts bunyaviral replication by limiting the pools of dcp2-accessible targets for cap-snatching.bunyaviruses are an emerging group of medically important viruses, many of which are transmitted from insects to mammals. to identify host factors that impact infection, we performed a genome-wide rnai screen in drosophila and identified 131 genes that impacted infection of the mosquito-transmitted bunyavirus rift valley fever virus (rvfv). dcp2, the catalytic component of the mrna decapping machinery, and two decapping activators, ddx6 and lsm7, were antiviral against disparate bunyaviruses in ...023824541
dicer-2- and piwi-mediated rna interference in rift valley fever virus-infected mosquito cells.rift valley fever virus (rvfv) is a phlebovirus (bunyaviridae family) transmitted by mosquitoes. it infects humans and ruminants, causing dramatic epidemics and epizootics in africa, yemen, and saudi arabia. while recent studies demonstrated the importance of the nonstructural protein nss as a major component of virulence in vertebrates, little is known about infection of mosquito vectors. here we studied rvfv infection in three different mosquito cell lines, aag2 cells from aedes aegypti and u4 ...201223175368
crystal structure of glycoprotein c from rift valley fever virus.rift valley fever virus (rvfv), like many other bunyaviridae family members, is an emerging human and animal pathogen. bunyaviruses have an outer lipid envelope bearing two glycoproteins, g(n) and g(c), required for cell entry. bunyaviruses deliver their genome into the host-cell cytoplasm by fusing their envelope with an endosomal membrane. the molecular mechanism of this key entry step is unknown. the crystal structure of rvfv g(c) reveals a class ii fusion protein architecture found previousl ...201323319635
crystal structure of glycoprotein c from a hantavirus in the post-fusion conformation.hantaviruses are important emerging human pathogens and are the causative agents of serious diseases in humans with high mortality rates. like other members in the bunyaviridae family their m segment encodes two glycoproteins, gn and gc, which are responsible for the early events of infection. hantaviruses deliver their tripartite genome into the cytoplasm by fusion of the viral and endosomal membranes in response to the reduced ph of the endosome. unlike phleboviruses (e.g. rift valley fever vi ...201627783673
the role of phlebovirus glycoproteins in viral entry, assembly and release.bunyaviruses are enveloped viruses with a tripartite rna genome that can pose a serious threat to animal and human health. members of the phlebovirus genus of the family bunyaviridae are transmitted by mosquitos and ticks to humans and include highly pathogenic agents like rift valley fever virus (rvfv) and severe fever with thrombocytopenia syndrome virus (sftsv) as well as viruses that do not cause disease in humans, like uukuniemi virus (uukv). phleboviruses and other bunyaviruses use their e ...201627455305
serum levels of inflammatory cytokines in rift valley fever patients are indicative of severe disease.rift valley fever (rvf) is a mosquito-borne viral zoonosis affecting domestic and wild ruminants, camels and humans. outbreaks of rvf are characterized by a sudden onset of abortions and high mortality amongst domestic ruminants. humans develop disease ranging from a mild flu-like illness to more severe complications including hemorrhagic syndrome, ocular and neurological lesions and death. during the rvf outbreak in south africa in 2010/11, a total of 278 human cases were laboratory confirmed, ...201526437779
rnasek is required for internalization of diverse acid-dependent viruses.viruses must gain entry into cells to establish infection. in general, viruses enter either at the plasma membrane or from intracellular endosomal compartments. viruses that use endosomal pathways are dependent on the cellular factors that control this process; however, these genes have proven to be essential for endogenous cargo uptake, and thus are of limited value for therapeutic intervention. the identification of genes that are selectively required for viral uptake would make appealing drug ...201526056282
virus-induced translational arrest through 4ebp1/2-dependent decay of 5'-top mrnas restricts viral infection.the mosquito-transmitted bunyavirus, rift valley fever virus (rvfv), is a highly successful pathogen for which there are no vaccines or therapeutics. translational arrest is a common antiviral strategy used by hosts. in response, rvfv inhibits two well-known antiviral pathways that attenuate translation during infection, pkr and type i ifn signaling. despite this, translational arrest occurs during rvfv infection by unknown mechanisms. here, we find that rvfv infection triggers the decay of core ...201526038567
stem-loop recognition by ddx17 facilitates mirna processing and antiviral defense.dead-box helicases play essential roles in rna metabolism across species, but emerging data suggest that they have additional functions in immunity. through rnai screening, we identify an evolutionarily conserved and interferon-independent role for the dead-box helicase ddx17 in restricting rift valley fever virus (rvfv), a mosquito-transmitted virus in the bunyavirus family that causes severe morbidity and mortality in humans and livestock. loss of drosophila ddx17 (rm62) in cells and flies enh ...025126784
rift valley fever virus encephalitis is associated with an ineffective systemic immune response and activated t cell infiltration into the cns in an immunocompetent mouse model.rift valley fever virus (rvfv) causes outbreaks of severe disease in livestock and humans throughout africa and the arabian peninsula. in people, rvfv generally causes a self-limiting febrile illness but in a subset of individuals, it progresses to more serious disease. one manifestation is a delayed-onset encephalitis that can be fatal or leave the afflicted with long-term neurologic sequelae. in order to design targeted interventions, the basic pathogenesis of rvfv encephalitis must be better ...201424922480
the role of ikkβ in venezuelan equine encephalitis virus infection.venezuelan equine encephalitis virus (veev) belongs to the genus alphavirus, family togaviridae. veev infection is characterized by extensive inflammation and studies from other laboratories implicated an involvement of the nf-κb cascade in the in vivo pathology. initial studies indicated that at early time points of veev infection, the nf-κb complex was activated in cells infected with the tc-83 strain of veev. one upstream kinase that contributes to the phosphorylation of p65 is the ikkβ compo ...201424586253
antiviral autophagy restrictsrift valley fever virus infection and is conserved from flies to mammals.autophagy has been implicated as a component of host defense, but the significance of antimicrobial autophagy in vivo and the mechanism by which it is regulated during infection are poorly defined. here we found that antiviral autophagy was conserved in flies and mammals during infection with rift valley fever virus (rvfv), a mosquito-borne virus that causes disease in humans and livestock. in drosophila, toll-7 limited rvfv replication and mortality through activation of autophagy. rvfv infecti ...201324374193
protein kinase r degradation is essential for rift valley fever virus infection and is regulated by skp1-cul1-f-box (scf)fbxw11-nss e3 ligase.activated protein kinase r (pkr) plays a vital role in antiviral defense primarily by inhibiting protein synthesis and augmenting interferon responses. many viral proteins have adopted unique strategies to counteract the deleterious effects of pkr. the nss (non-structural s) protein which is encoded by rift valley fever virus (rvfv) promotes early pkr proteasomal degradation through a previously undefined mechanism. in this study, we demonstrate that nss carries out this activity by assembling t ...201626837067
β-catenin upregulates the constitutive and virus-induced transcriptional capacity of the interferon beta promoter through t-cell factor binding sites.rapid upregulation of interferon beta (ifn-β) expression following virus infection is essential to set up an efficient innate antiviral response. biological roles related to the antiviral and immune response have also been associated with the constitutive production of ifn-β in naive cells. however, the mechanisms capable of modulating constitutive ifn-β expression in the absence of infection remain largely unknown. in this work, we demonstrate that inhibition of the kinase glycogen synthase kin ...201526459757
nonspreading rift valley fever virus infection of human dendritic cells results in downregulation of cd83 and full maturation of bystander cells.vaccines based on nonspreading rift valley fever virus (nsr) induce strong humoral and robust cellular immune responses with pronounced th1 polarisation. the present work was aimed to gain insight into the molecular basis of nsr-mediated immunity. recent studies have demonstrated that wild-type rift valley fever virus efficiently targets and replicates in dendritic cells (dcs). we found that nsr infection of cultured human dcs results in maturation of dcs, characterized by surface upregulation o ...201526575844
high content image-based screening of a protease inhibitor library reveals compounds broadly active against rift valley fever virus and other highly pathogenic rna viruses.high content image-based screening was developed as an approach to test a protease inhibitor small molecule library for antiviral activity against rift valley fever virus (rvfv) and to determine their mechanism of action. rvfv is the causative agent of severe disease of humans and animals throughout africa and the arabian peninsula. of the 849 compounds screened, 34 compounds exhibited ≥ 50% inhibition against rvfv. all of the hit compounds could be classified into 4 distinct groups based on the ...201425144302
single-dose immunization with virus replicon particles confers rapid robust protection against rift valley fever virus challenge.rift valley fever virus (rvfv) causes outbreaks of severe disease in people and livestock throughout africa and the arabian peninsula. the potential for rvfv introduction outside the area of endemicity highlights the need for fast-acting, safe, and efficacious vaccines. here, we demonstrate a robust system for the reverse genetics generation of a rvf virus replicon particle (vrp(rvf)) vaccine candidate. using a mouse model, we show that vrp(rvf) immunization provides the optimal balance of safet ...201222345465
vaccines for viral hemorrhagic fevers--progress and shortcomings.with a few exceptions, vaccines for viruses that cause hemorrhagic fever remain unavailable or lack well-documented efficacy. in the past decade this has not been due to a lack of the ability to develop vaccine platforms against highly pathogenic viruses, but rather the lack of will/interest to invest in platforms that have the potential to become successful vaccines. the two exceptions to this are vaccines against dengue virus (denv) and rift valley fever virus (rvfv), which recently have seen ...201323773330
rift valley fever virus clearance and protection from neurologic disease are dependent on cd4+ t cell and virus-specific antibody responses.rift valley fever virus (rvfv) causes outbreaks of severe disease in people and livestock throughout africa and the arabian peninsula. human rvfv infections generally manifest as a self-limiting febrile illness, but in some individuals, the disease can progress to a fatal encephalitis or hemorrhagic syndrome. little is known about the host characteristics that predispose development of more severe disease. early in infection, interferon-mediated antiviral responses are critical for controlling r ...201323536675
novel approaches to develop rift valley fever vaccines.rift valley fever (rvf) is endemic to sub-saharan africa, and has spread into madagascar, egypt, saudi arabia, and yemen. rift valley fever virus (rvfv) of the family bunyaviridae, genus phlebovirus causes hemorrhagic fever, neurological disorders or blindness in humans, and high rate abortion and fetal malformation in ruminants. rvfv is classified as a category a priority pathogen and overlap select agent by cdc/usda due to its potential impact on public health and agriculture. there is a gap i ...201223112960
favipiravir (t-705), a novel viral rna polymerase inhibitor.favipiravir (t-705; 6-fluoro-3-hydroxy-2-pyrazinecarboxamide) is an antiviral drug that selectively inhibits the rna-dependent rna polymerase of influenza virus. it is phosphoribosylated by cellular enzymes to its active form, favipiravir-ribofuranosyl-5'-triphosphate (rtp). its antiviral effect is attenuated by the addition of purine nucleic acids, indicating the viral rna polymerase mistakenly recognizes favipiravir-rtp as a purine nucleotide. favipiravir is active against a broad range of inf ...201324084488
outbreak of viral hemorrhagic fever caused by dengue virus type 3 in al-mukalla, yemen.investigations were conducted by the authors to explore an outbreak of viral hemorrhagic fever (vhf) reported in 2010 from al-mukalla city, the capital of hadramout in yemen.201323497142
predicting the mosquito species and vertebrate species involved in the theoretical transmission of rift valley fever virus in the united states.rift valley fever virus (rvfv) is a mosquito-borne virus in the family bunyaviridiae that has spread throughout continental africa to madagascar and the arabian peninsula. the establishment of rvfv in north america would have serious consequences for human and animal health in addition to a significant economic impact on the livestock industry. published and unpublished data on rvfv vector competence, vertebrate host competence, and mosquito feeding patterns from the united states were combined ...201425211133
ecological niche modeling and land cover risk areas for rift valley fever vector, culex tritaeniorhynchus giles in jazan, saudi arabia.the mosquito, culex tritaeniorhynchus giles is a prevalent and confirmed rift valley fever virus (rvfv) vector. this vector, in association with aedimorphus arabiensis (patton), was responsible for causing the outbreak of 2000 in jazan province, saudi arabia.201323762424
seroepidemiological study of west nile virus and rift valley fever virus in some of mammalian species (herbivores) in northern turkey.west nile virus (wnv) and rift valley fever virus (rvfv) are mosquito-borne viral diseases. the objective of this study was to investigate the rvfv and wnv infections as serologically in different mammalian species (cattle, horse, goat, sheep and water buffalo) in the northern turkey.201323785699
a multiplex pcr/ldr assay for the simultaneous identification of category a infectious pathogens: agents of viral hemorrhagic fever and variola virus.cdc designated category a infectious agents pose a major risk to national security and require special action for public health preparedness. they include viruses that cause viral hemorrhagic fever (vhf) syndrome as well as variola virus, the agent of smallpox. vhf is characterized by hemorrhage and fever with multi-organ failure leading to high morbidity and mortality. smallpox, a prior scourge, has been eradicated for decades, making it a particularly serious threat if released nefariously in ...201526381398
the risk of rift valley fever virus introduction and establishment in the united states and european union.rift valley fever virus (rvfv) is an arthropod-borne disease resulting in severe morbidity and mortality in both human and ruminant populations. first identified in kenya in 1930, the geographical range of rvfv has been largely constrained to the african continent, yet has recently spread to new regions, and is identified as a priority disease with potential for geographic emergence. we present a systematic literature review assessing the potential for rvfv introduction and establishment in the ...201326038446
temperature-sensitive mutations for live-attenuated rift valley fever vaccines: implications from other rna viruses.rift valley fever (rvf) is a mosquito-borne zoonotic disease endemic to the african continent. rvf is characterized by high rate of abortions in ruminants and hemorrhagic fever, encephalitis, or blindness in humans. rvf is caused by the rift valley fever virus (rvfv: genus phlebovirus, family bunyaviridae). vaccination is the only known effective strategy to prevent the disease, but there are no licensed rvf vaccines available for humans. a live-attenuated vaccine candidate derived from the wild ...201526322023
ecological niche modelling of rift valley fever virus vectors in baringo, kenya.rift valley fever (rvf) is a vector-borne zoonotic disease that has an impact on human health and animal productivity. here, we explore the use of vector presence modelling to predict the distribution of rvf vector species under climate change scenario to demonstrate the potential for geographic spread of rift valley fever virus (rvfv).201627863533
ebola vp40 in exosomes can cause immune cell dysfunction.ebola virus (ebov) is an enveloped, ssrna virus from the family filoviridae capable of causing severe hemorrhagic fever with up to 80-90% mortality rates. the most recent outbreak of ebov in west africa starting in 2014 resulted in over 11,300 deaths; however, long-lasting persistence and recurrence in survivors has been documented, potentially leading to further transmission of the virus. we have previously shown that exosomes from cells infected with hiv-1, htlv-1 and rift valley fever virus a ...201627872619
recent weather extremes and impacts on agricultural production and vector-borne disease outbreak patterns.we document significant worldwide weather anomalies that affected agriculture and vector-borne disease outbreaks during the 2010-2012 period. we utilized 2000-2012 vegetation index and land surface temperature data from nasa's satellite-based moderate resolution imaging spectroradiometer (modis) to map the magnitude and extent of these anomalies for diverse regions including the continental united states, russia, east africa, southern africa, and australia. we demonstrate that shifts in temperat ...201424658301
data-driven modeling to assess receptivity for rift valley fever virus.rift valley fever virus (rvfv) is an enzootic virus that causes extensive morbidity and mortality in domestic ruminants in africa, and it has shown the potential to invade other areas such as the arabian peninsula. here, we develop methods for linking mathematical models to real-world data that could be used for continent-scale risk assessment given adequate data on local host and vector populations. we have applied the methods to a well-studied agricultural region of california with [formula: s ...201324244769
seroprevalence of infections with dengue, rift valley fever and chikungunya viruses in kenya, 2007.arthropod-borne viruses are a major constituent of emerging infectious diseases worldwide, but limited data are available on the prevalence, distribution, and risk factors for transmission in kenya and east africa. in this study, we used 1,091 hiv-negative blood specimens from the 2007 kenya aids indicator survey (kais 2007) to test for the presence of igg antibodies to dengue virus (denv), chikungunya virus (chikv) and rift valley fever virus (rvfv).the kais 2007 was a national population-based ...201526177451
a stochastic model to study rift valley fever persistence with different seasonal patterns of vector abundance: new insights on the endemicity in the tropical island of mayotte.rift valley fever (rvf) is a zoonotic vector-borne disease causing abortion storms in cattle and human epidemics in africa. our aim was to evaluate rvf persistence in a seasonal and isolated population and to apply it to mayotte island (indian ocean), where the virus was still silently circulating four years after its last known introduction in 2007. we proposed a stochastic model to estimate rvf persistence over several years and under four seasonal patterns of vector abundance. firstly, the mo ...201526147799
comparison of rift valley fever virus replication in north american livestock and wildlife cell lines.rift valley fever virus (rvfv) causes disease outbreaks across africa and the arabian peninsula, resulting in high morbidity and mortality among young domestic livestock, frequent abortions in pregnant animals, and potentially severe or fatal disease in humans. the possibility of rvfv spreading to the united states or other countries worldwide is of significant concern to animal and public health, livestock production, and trade. the mechanism for persistence of rvfv during inter-epidemic period ...201526175725
first report of l1014f-kdr mutation in culex pipiens complex from morocco.mosquitoes of the culex pipiens complex, competent vectors for west nile virus (wnv) and rift valley fever virus (rvfv) are widely targeted by insecticide treatments. the intensive application of chemical insecticides led to the development of resistance in many insects including culex pipiens mosquitoes. the absence of data on resistance mechanisms in morocco allow us to assess the levels of lambda-cyhalothrin resistance and the frequency of the mutated gene l1014f kdr in different forms of cx. ...201627986090
serological evidence of contrasted exposure to arboviral infections between islands of the union of comoros (indian ocean).a cross sectional serological survey of arboviral infections in humans was conducted on the three islands of the union of comoros, indian ocean, in order to test a previously suggested contrasted exposure of the three neighboring islands to arthropod-borne epidemics. four hundred human sera were collected on ngazidja (grande comore), mwali (mohéli) and ndzouani (anjouan), and were tested by elisa for igm and/or igg antibodies to dengue (denv), chikungunya (chikv), rift valley fever (rvfv), west ...201627977670
rift valley fever virus mp-12 vaccine encoding toscana virus nss retains neuroinvasiveness in mice.rift valley fever is a mosquito-borne zoonotic disease endemic to sub-saharan africa. rift valley fever virus (rvfv; genus phlebovirus, family bunyaviridae) causes high rates of abortion and fetal malformation in pregnant ruminants, and haemorrhagic fever, neurological disorders or blindness in humans. the mp-12 strain is a highly efficacious and safe live-attenuated vaccine candidate for both humans and ruminants. however, mp-12 lacks a marker to differentiate infected from vaccinated animals. ...201323515022
aedes mosquito saliva modulates rift valley fever virus pathogenicity.rift valley fever (rvf) is a severe mosquito-borne disease affecting humans and domestic ruminants. mosquito saliva contains compounds that counteract the hemostatic, inflammatory, and immune responses of the host. modulation of these defensive responses may facilitate virus infection. indeed, aedes mosquito saliva played a crucial role in the vector's capacity to effectively transfer arboviruses such as the cache valley and west nile viruses. the role of mosquito saliva in the transmission of r ...201323785528
culex pipiens, an experimental efficient vector of west nile and rift valley fever viruses in the maghreb region.west nile fever (wnf) and rift valley fever (rvf) are emerging diseases causing epidemics outside their natural range of distribution. west nile virus (wnv) circulates widely and harmlessly in the old world among birds as amplifying hosts, and horses and humans as accidental dead-end hosts. rift valley fever virus (rvfv) re-emerges periodically in africa causing massive outbreaks. in the maghreb, eco-climatic and entomologic conditions are favourable for wnv and rvfv emergence. both viruses are ...201222693557
factors associated with severe human rift valley fever in sangailu, garissa county, kenya.mosquito-borne rift valley fever virus (rvfv) causes acute, often severe, disease in livestock and humans. to determine the exposure factors and range of symptoms associated with human rvf, we performed a population-based cross-sectional survey in six villages across a 40 km transect in northeastern kenya.201525764399
serologic evidence of exposure to rift valley fever virus detected in tunisia.rift valley fever virus (rvfv) is capable of causing dramatic outbreaks amongst economically important animal species and is capable of causing severe symptoms and mortality in humans. rvfv is known to circulate widely throughout east africa; serologic evidence of exposure has also been found in some northern african countries, including mauritania. this study aimed to ascertain whether rvfv is circulating in regions beyond its known geographic range. samples from febrile patients (n = 181) and ...201526740887
emerging infections of cns: avian influenza a virus, rift valley fever virus and human parechovirus.history is replete with emergent pandemic infections that have decimated the human population. given the shear mass of humans that now crowd the earth, there is every reason to suspect history will repeat itself. we describe three rna viruses that have recently emerged in the human population to mediate severe neurological disease. these new diseases are results of new mutations in the infectious agents or new exposure pathways to the agents or both. to appreciate their pathogenesis, we summariz ...026276027
ifitms restrict the replication of multiple pathogenic viruses.the interferon-inducible transmembrane protein (ifitm) family inhibits a growing number of pathogenic viruses, among them influenza a virus, dengue virus, hepatitis c virus, and ebola virus. this review covers recent developments in our understanding of the ifitm's molecular determinants, potential mechanisms of action, and impact on pathogenesis.201324076421
ifitm-2 and ifitm-3 but not ifitm-1 restrict rift valley fever virus.we show that interferon-induced transmembrane protein 1 (ifitm-1), ifitm-2, and ifitm-3 exhibit a broad spectrum of antiviral activity against several members of the bunyaviridae family, including rift valley fever virus (rvfv), la crosse virus, andes virus, and hantaan virus, all of which can cause severe disease in humans and animals. we found that rvfv was restricted by ifitm-2 and -3 but not by ifitm-1, whereas the remaining viruses were equally restricted by all ifitms. indeed, at low doses ...201323720721
a sero-epidemiological study of arboviral fevers in djibouti, horn of africa.arboviral infections have repeatedly been reported in the republic of djibouti, consistent with the fact that essential vectors for arboviral diseases are endemic in the region. however, there is a limited recent information regarding arbovirus circulation, and the associated risk predictors to human exposure are largely unknown. we performed, from november 2010 to february 2011 in the djibouti city general population, a cross-sectional elisa and sero-neutralisation-based sero-epidemiological an ...201425502692
a spatially explicit metapopulation model and cattle trade analysis suggests key determinants for the recurrent circulation of rift valley fever virus in a pilot area of madagascar highlands.rift valley fever (rvf) is a vector-borne zoonotic disease that causes high morbidity and mortality in ruminants. in 2008-2009, a rvf outbreak affected the whole madagascar island, including the anjozorobe district located in madagascar highlands. an entomological survey showed the absence of aedes among the potential rvf virus (rvfv) vector species identified in this area, and an overall low abundance of mosquitoes due to unfavorable climatic conditions during winter. no serological nor virolog ...201425474116
a hierarchical network approach for modeling rift valley fever epidemics with applications in north america.rift valley fever is a vector-borne zoonotic disease which causes high morbidity and mortality in livestock. in the event rift valley fever virus is introduced to the united states or other non-endemic areas, understanding the potential patterns of spread and the areas at risk based on disease vectors and hosts will be vital for developing mitigation strategies. presented here is a general network-based mathematical model of rift valley fever. given a lack of empirical data on disease vector spe ...201323667453
rna helicase signaling is critical for type i interferon production and protection against rift valley fever virus during mucosal challenge.rift valley fever virus (rvfv) is an emerging rna virus with devastating economic and social consequences. clinically, rvfv induces a gamut of symptoms ranging from febrile illness to retinitis, hepatic necrosis, hemorrhagic fever, and death. it is known that type i interferon (ifn) responses can be protective against severe pathology; however, it is unknown which innate immune receptor pathways are crucial for mounting this response. using both in vitro assays and in vivo mucosal mouse challeng ...201323408632
inter-epidemic and between-season persistence of rift valley fever: vertical transmission or cryptic cycling?rift valley fever (rvf) is an emerging zoonotic mosquito-borne infectious disease that has been identified as a risk for spread to other continents and can cause mass livestock mortality. in equatorial africa, outbreaks of rvf are associated with high rainfall, when vector populations are at their highest. it is, however, unclear how rvf virus persists during the inter-epidemic periods and between seasons. understanding inter-epidemic persistence as well as the role of vectors and hosts is param ...201323551913
rift valley fever virus incorporates the 78 kda glycoprotein into virions matured in mosquito c6/36 cells.rift valley fever virus (rvfv), genus phlebovirus, family bunyaviridae is a zoonotic arthropod-borne virus able to transition between distant host species, causing potentially severe disease in humans and ruminants. viral proteins are encoded by three genomic segments, with the medium m segment coding for four proteins: nonstructural nsm protein, two glycoproteins gn and gc and large 78 kda glycoprotein (lgp) of unknown function. goat anti-rvfv polyclonal antibody and mouse monoclonal antibody, ...201424489907
rift valley fever virus infection in golden syrian hamsters.rift valley fever virus (rvfv) is a formidable pathogen that causes severe disease and abortion in a variety of livestock species and a range of disease in humans that includes hemorrhagic fever, fulminant hepatitis, encephalitis and blindness. the natural transmission cycle involves mosquito vectors, but exposure can also occur through contact with infected fluids and tissues. the lack of approved antiviral therapies and vaccines for human use underlies the importance of small animal models for ...201525607955
multi-faceted proteomic characterization of host protein complement of rift valley fever virus virions and identification of specific heat shock proteins, including hsp90, as important viral host factors.rift valley fever is a potentially fatal disease of humans and domestic animals caused by rift valley fever virus (rvfv). infection with rvfv in ruminants can cause near 100% abortion rates and recent outbreaks in naïve human populations have suggested case fatality rates of greater than thirty percent. to elucidate the roles that host proteins play during rvfv infection, proteomic analysis of rvfv virions was conducted using complementary analytical approaches, followed by functional validation ...201424809507
ecological differentiation of members of the culex pipiens complex, potential vectors of west nile virus and rift valley fever virus in algeria.we investigated the ecological differentiation of two members of the culex pipiens complex, cx. p. pipiens form pipiens and cx. p. pipiens form molestus in three sites, el-kala, m'sila and tinerkouk in algeria. these two forms are the most widespread mosquito vectors in temperate regions exhibiting important behavioural and physiological differences. nevertheless, this group of potential vectors has been poorly studied, particularly in north africa.201627534938
development of real-time reverse transcriptase qpcr assays for the detection of punta toro virus and pichinde virus.research with high biocontainment pathogens such as rift valley fever virus (rvfv) and lassa virus (lasv) is expensive, potentially hazardous, and limited to select institutions. surrogate pathogens such as punta toro virus (ptv) for rvfv infection and pichinde virus (picv) for lasv infection allow research to be performed under more permissive bsl-2 conditions. although used as infection models, ptv and picv have no standard real-time rt-qpcr assays to detect and quantify pathogenesis. ptv is a ...201627029488
transmission dynamics of rift valley fever virus: effects of live and killed vaccines on epizootic outbreaks and enzootic maintenance.rift valley fever virus (rvfv) is an arthropod-borne viral pathogen that causes significant morbidity and mortality in small ruminants throughout africa and the middle east. due to the sporadic and explosive nature of rvf outbreaks, vaccination has proved challenging to reduce rvfv infection in the ruminant population. currently, there are two available types of vaccines, live and killed, in endemic areas. in this study, two mathematical models have been developed to explore the impact of live a ...201626869999
inflammatory biomarkers associated with lethal rift valley fever encephalitis in the lewis rat model.rift valley fever (rvf) is an emerging viral disease that causes significant human and veterinary illness in africa and the arabian peninsula. encephalitis is one of the severe complications arising from rvf virus (rvfv) infection of people, and the pathogenesis of this form of rvf is completely unknown. we use a novel reproducible encephalitic disease model in rats to identify biomarkers of lethal infection. lewis rats were infected with rvfv strain zh501 by aerosol exposure, then sacrificed da ...201626779164
a genome-wide rna interference screen identifies a role for wnt/β-catenin signaling during rift valley fever virus infection.rift valley fever virus (rvfv) is an arbovirus within the bunyaviridae family capable of causing serious morbidity and mortality in humans and livestock. to identify host factors involved in bunyavirus replication, we employed genome-wide rna interference (rnai) screening and identified 381 genes whose knockdown reduced infection. the wnt pathway was the most represented pathway when gene hits were functionally clustered. with further investigation, we found that rvfv infection activated wnt sig ...201627226375
has rift valley fever virus evolved with increasing severity in human populations in east africa?rift valley fever (rvf) outbreaks have occurred across eastern africa from 1912 to 2010 approximately every 4-15 years, most of which have not been accompanied by significant epidemics in human populations. however, human epidemics during rvf outbreaks in eastern africa have involved 478 deaths in 1998, 1107 reported cases with 350 deaths from 2006 to 2007 and 1174 cases with 241 deaths in 2008. we review the history of rvf outbreaks in eastern africa to identify the epidemiological factors that ...201627329846
biochemical and biophysical characterization of cell-free synthesized rift valley fever virus nucleoprotein capsids enables in vitro screening to identify novel antivirals.viral capsid assembly involves the oligomerization of the capsid nucleoprotein (np), which is an essential step in viral replication and may represent a potential antiviral target. an in vitro transcription-translation reaction using a wheat germ (wg) extract in combination with a sandwich elisa assay has recently been used to identify small molecules with antiviral activity against the rabies virus.201627179769
sheep skin odor improves trap captures of mosquito vectors of rift valley recent years, the east african region has seen an increase in arboviral diseases transmitted by blood-feeding arthropods. effective surveillance to monitor and reduce incidence of these infections requires the use of appropriate vector sampling tools. here, trapped skin volatiles on fur from sheep, a known preferred host of mosquito vectors of rift valley fever virus (rvfv), were used with a standard cdc light trap to improve catches of mosquito vectors. we tested the standard cdc light trap ...201223133687
skip the alignment: degenerate, multiplex primer and probe design using k-mer matching instead of alignments.primux is a new software package for selecting multiplex compatible, degenerate primers and probes to detect diverse targets such as viruses. it requires no multiple sequence alignment, instead applying k-mer algorithms, hence it scales well for large target sets and saves user effort from curating sequences into alignable groups. primux has the capability to predict degenerate primers as well as probes suitable for taqman or other primer/probe triplet assay formats, or simply probes for microar ...201222485178
community knowledge and attitudes and health workers' practices regarding non-malaria febrile illnesses in eastern tanzania.although malaria has been the leading cause of fever for many years, with improved control regimes malaria transmission, morbidity and mortality have decreased. recent studies have increasingly demonstrated the importance of non-malaria fevers, which have significantly improved our understanding of etiologies of febrile illnesses. a number of non-malaria febrile illnesses including rift valley fever, dengue fever, chikungunya virus infection, leptospirosis, tick-borne relapsing fever and q-fever ...201424852787
blood meal analysis and virus detection in blood-fed mosquitoes collected during the 2006-2007 rift valley fever outbreak in kenya.rift valley fever (rvf) is a zoonosis of domestic ruminants in africa. blood-fed mosquitoes collected during the 2006-2007 rvf outbreak in kenya were analyzed to determine the virus infection status and animal source of the blood meals.025229704
reemergence of rift valley fever, mauritania, 2010.a rift valley fever (rvf) outbreak in humans and animals occurred in mauritania in 2010. thirty cases of rvf in humans and 3 deaths were identified. rvfv isolates were recovered from humans, camels, sheep, goats, and culex antennatus mosquitoes. phylogenetic analysis of isolates indicated a virus origin from western africa.024447381
rift valley fever vector diversity and impact of meteorological and environmental factors on culex pipiens dynamics in the okavango delta, northern botswana, rural communities, livestock, wildlife and large numbers of mosquitoes cohabitate around permanent waters of the okavango delta. as in other regions of sub-saharan africa, rift valley fever (rvf) virus is known to circulate in that area among wild and domestic animals. however, the diversity and composition of potential rvf mosquito vectors in that area are unknown as well as the climatic and ecological drivers susceptible to affect their population dynamics.201627502246
modelling the effects of seasonality and socioeconomic impact on the transmission of rift valley fever virus.rift valley fever (rvf) is an important mosquito-borne viral zoonosis in africa and the middle east that causes human deaths and significant economic losses due to huge incidences of death and abortion among infected livestock. outbreaks of rvf are sporadic and associated with both seasonal and socioeconomic effects. here we propose an almost periodic three-patch model to investigate the transmission dynamics of rvf virus (rvfv) among ruminants with spatial movements. our findings indicate that, ...201525569474
toscana virus nss protein promotes degradation of double-stranded rna-dependent protein kinase.toscana virus (tosv), which is transmitted by phlebotomus spp. sandflies, is a major etiologic agent of aseptic meningitis and encephalitis in the mediterranean. like other members of the genus phlebovirus of the family bunyaviridae, tosv encodes a nonstructural protein (nss) in its small rna segment. although the nss of rift valley fever virus (rvfv) has been identified as an important virulence factor, which suppresses host general transcription, inhibits transcription from the beta interferon ...201323325696
mosquito host choices on livestock amplifiers of rift valley fever virus in kenya.animal hosts may vary in their attraction and acceptability as components of the host location process for assessing preference, and biting rates of vectors and risk of exposure to pathogens. however, these parameters remain poorly understood for mosquito vectors of the rift valley fever (rvf), an arboviral disease, and for a community of mosquitoes.201627036889
recent outbreaks of rift valley fever in east africa and the middle east.rift valley fever (rvf) is an important neglected, emerging, mosquito-borne disease with severe negative impact on human and animal health. mosquitoes in the aedes genus have been considered as the reservoir, as well as vectors, since their transovarially infected eggs withstand desiccation and larvae hatch when in contact with water. however, different mosquito species serve as epizootic/epidemic vectors of rvf, creating a complex epidemiologic pattern in east africa. the recent rvf outbreaks i ...201425340047
towards a better understanding of rift valley fever epidemiology in the south-west of the indian ocean.rift valley fever virus (phlebovirus, bunyaviridae) is an arbovirus causing intermittent epizootics and sporadic epidemics primarily in east africa. infection causes severe and often fatal illness in young sheep, goats and cattle. domestic animals and humans can be contaminated by close contact with infectious tissues or through mosquito infectious bites. rift valley fever virus was historically restricted to sub-saharan countries. the probability of rift valley fever emerging in virgin areas is ...201324016237
modelling hotspots of the two dominant rift valley fever vectors (aedes vexans and culex poicilipes) in barkédji, sénégal.climatic and environmental variables were used successfully by using models to predict rift valley fever (rvf) virus outbreaks in east africa. however, these models are not replicable in the west african context due to a likely difference of the dynamic of the virus emergence. for these reasons specific models mainly oriented to the risk mapping have been developed. hence, the areas of high vector pressure or virus activity are commonly predicted. however, the factors impacting their occurrence ...201626922792
rift valley fever outbreak, southern mauritania, 2012.after a period of heavy rainfall, an outbreak of rift valley fever occurred in southern mauritania during september-november 2012. a total of 41 human cases were confirmed, including 13 deaths, and 12 rift valley fever virus strains were isolated. moudjeria and temchecket departments were the most affected areas.024447334
common host-derived chemicals increase catches of disease-transmitting mosquitoes and can improve early warning systems for rift valley fever virus.rift valley fever (rvf), a mosquito-borne zoonosis, is a major public health and veterinary problem in sub-saharan africa. surveillance to monitor mosquito populations during the inter-epidemic period (iep) and viral activity in these vectors is critical to informing public health decisions for early warning and control of the disease. using a combination of field bioassays, electrophysiological and chemical analyses we demonstrated that skin-derived aldehydes (heptanal, octanal, nonanal, decana ...201323326620
unexpected rift valley fever outbreak, northern mauritania.during september-october 2010, an unprecedented outbreak of rift valley fever was reported in the northern sahelian region of mauritania after exceptionally heavy rainfall. camels probably played a central role in the local amplification of the virus. we describe the main clinical signs (hemorrhagic fever, icterus, and nervous symptoms) observed during the outbreak.022000364
the epidemiology of rift valley fever in mayotte: insights and perspectives from 11 years of data.rift valley fever (rvf) is a zoonotic arboviral disease that is a threat to human health, animal health and production, mainly in sub-saharan africa. rvf virus dynamics have been poorly studied due to data scarcity. on the island of mayotte in the indian ocean, off the southeastern african coast, rvf has been present since at least 2004. several retrospective and prospective serological surveys in livestock have been conducted over eleven years (2004-15). these data are collated and presented he ...201627331402
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