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comprehensive molecular detection of tick-borne phleboviruses leads to the retrospective identification of taxonomically unassigned bunyaviruses and the discovery of a novel member of the genus phlebovirus.until the recent emergence of two human-pathogenic tick-borne phleboviruses (tbpvs) (severe fever with thrombocytopenia syndrome virus [sftsv] and heartland virus), tbpvs have been neglected as causative agents of human disease. in particular, no studies have addressed the global distribution of tbpvs, and consequently, our understanding of the mechanism(s) underlying their evolution and emergence remains poor. in order to provide a useful tool for the ecological and epidemiological study of tbp ...201425339769
the genome sequence of lone star virus, a highly divergent bunyavirus found in the amblyomma americanum tick.viruses in the family bunyaviridae infect a wide range of plant, insect, and animal hosts. tick-borne bunyaviruses in the phlebovirus genus, including severe fever with thrombocytopenia syndrome virus (sftsv) in china, heartland virus (hrtv) in the united states, and bhanja virus in eurasia and africa have been associated with acute febrile illness in humans. here we sought to characterize the growth characteristics and genome of lone star virus (lsv), an unclassified bunyavirus originally isola ...201323637969
serological investigation of heartland virus (bunyaviridae: phlebovirus) exposure in wild and domestic animals adjacent to human case sites in missouri 2012-2013.heartland virus (hrtv; bunyaviridae: phlebovirus) has recently emerged as a causative agent of human disease characterized by thrombocytopenia and leukopenia in the united states. the lone star tick (amblyomma americanum l.) has been implicated as a vector. to identify candidate vertebrate amplification hosts associated with enzootic maintenance of the virus, sera and ticks were sampled from 160 mammals (8 species) and 139 birds (26 species) captured near 2 human case residences in andrew and no ...201525870419
cell culture and electron microscopy for identifying viruses in diseases of unknown cause.during outbreaks of infectious diseases or in cases of severely ill patients, it is imperative to identify the causative agent. this report describes several events in which virus isolation and identification by electron microscopy were critical to initial recognition of the etiologic agent, which was further analyzed by additional laboratory diagnostic assays. examples include severe acute respiratory syndrome coronavirus, and nipah, lymphocytic choriomeningitis, west nile, cache valley, and he ...023731788
novel thogotovirus associated with febrile illness and death, united states, 2014.a previously healthy man from eastern kansas, usa, sought medical care in late spring because of a history of tick bite, fever, and fatigue. the patient had thrombocytopenia and leukopenia and was given doxycycline for a presumed tickborne illness. his condition did not improve. multiorgan failure developed, and he died 11 days after illness onset from cardiopulmonary arrest. molecular and serologic testing results for known tickborne pathogens were negative. however, testing of a specimen for a ...025899080
characterization of the uukuniemi virus group (phlebovirus: bunyaviridae): evidence for seven distinct species.evolutionary insights into the phleboviruses are limited because of an imprecise classification scheme based on partial nucleotide sequences and scattered antigenic relationships. in this report, the serologic and phylogenetic relationships of the uukuniemi group viruses and their relationships with other recently characterized tick-borne phleboviruses are described using full-length genome sequences. we propose that the viruses currently included in the uukuniemi virus group be assigned to five ...201323283959
generation of mutant uukuniemi viruses lacking the nonstructural protein nss by reverse genetics indicates that nss is a weak interferon antagonist.uukuniemi virus (uukv) is a tick-borne member of the phlebovirus genus (family bunyaviridae) and has been widely used as a safe laboratory model to study aspects of bunyavirus replication. recently, a number of new tick-borne phleboviruses have been discovered, some of which, like severe fever with thrombocytopenia syndrome virus and heartland virus, are highly pathogenic in humans. uukv could now serve as a useful comparator to understand the molecular basis for the different pathogenicities of ...201525673721
reverse genetics system for severe fever with thrombocytopenia syndrome virus.severe fever with thrombocytopenia syndrome virus (sftsv) is an emerging tick-borne pathogen that was first reported in china in 2009. phylogenetic analysis of the viral genome showed that sfts virus represents a new lineage within the phlebovirus genus, distinct from the existing sandfly fever and uukuniemi virus groups, in the family bunyaviridae. sfts disease is characterized by gastrointestinal symptoms, chills, joint pain, myalgia, thrombocytopenia, leukocytopenia, and some hemorrhagic mani ...201425552716
heartland virus neutralizing antibodies in vertebrate wildlife, united states, 2009-2014.since its discovery in 2009, the tickborne heartland virus (hrtv) has caused human illness in missouri, oklahoma, and tennessee usa. to better assess the geographic distribution of hrtv, we used wildlife serology as an indicator. this retrospective evaluation determined that hrtv is widespread within the central and eastern united states.026401988
first detection of heartland virus (bunyaviridae: phlebovirus) from field collected arthropods.heartland virus (hrtv), the first pathogenic phlebovirus (family: bunyaviridae) discovered in the united states, was recently described from two missouri farmers. in 2012, we collected 56,428 ticks representing three species at 12 sites including both patients' farms. amblyomma americanum and dermacentor variabilis accounted for nearly all ticks collected. ten pools composed of deplete nymphs of a. americanum collected at a patient farm and a nearby conservation area were reverse transcription-p ...201323878186
phleboviruses and the type i interferon response.the genus phlebovirus of the family bunyaviridae contains a number of emerging virus species which pose a threat to both human and animal health. most prominent members include rift valley fever virus (rvfv), sandfly fever naples virus (sfnv), sandfly fever sicilian virus (sfsv), toscana virus (tosv), punta toro virus (ptv), and the two new members severe fever with thrombocytopenia syndrome virus (sftsv) and heartland virus (hrtv). the nonstructural protein nss is well established as the main p ...201627338447
characterization of the bhanja serogroup viruses (bunyaviridae): a novel species of the genus phlebovirus and its relationship with other emerging tick-borne phleboviruses.bhanja virus (bhav) and its antigenically close relatives forecariah virus (forv), kismayo virus (kisv), and palma virus (palv) are thought to be members of the family bunyaviridae, but they have not been assigned to a genus or species. despite their broad geographical distribution and reports that bhav causes sporadic cases of febrile illness and encephalitis in humans, the public health importance of the bhanja serogroup viruses remains unclear, due in part to the lack of sequence and biochemi ...201323325688
vertebrate host susceptibility to heartland virus.heartland virus (hrtv) is a recently described phlebovirus initially isolated in 2009 from 2 humans who had leukopenia and thrombocytopenia. serologic assessment of domestic and wild animal populations near the residence of 1 of these persons showed high exposure rates to raccoons, white-tailed deer, and horses. to our knowledge, no laboratory-based assessments of viremic potential of animals infected with hrtv have been performed. we experimentally inoculated several vertebrates (raccoons, goat ...027869591
development and characterization of monoclonal antibodies directed against the nucleoprotein of heartland virus.heartland virus (hrtv), a phlebovirus first isolated from two missouri farmers in 2009, has been proposed to be transmitted to humans by the bite of infected amblyomma americanum ticks. it is closely related to severe fever with thrombocytopenia syndrome virus (sftsv) from china, another previously unrecognized phlebovirus that has subsequently been associated with hundreds of cases of severe disease in humans. to expand diagnostic capacity to detect hrtv infections, 20 hybridoma clones secretin ...201526503274
malsoor virus, a novel bat phlebovirus, is closely related to severe fever with thrombocytopenia syndrome virus and heartland virus.during a survey in the year 2010, a novel phlebovirus was isolated from the rousettus leschenaultii species of bats in western india. the virus was identified by electron microscopy from infected vero e6 cells. phylogenic analysis of the complete genome showed its close relation to severe fever with thrombocytopenia syndrome (sfts) and heartland viruses, which makes it imperative to further study its natural ecology and potential as a novel emerging zoonotic virus.201424390329
tick-borne viruses: a review from the perspective of therapeutic approaches.several important human diseases worldwide are caused by tick-borne viruses. these diseases have become important public health concerns in recent years. the tick-borne viruses that cause diseases in humans mainly belong to 3 families: bunyaviridae, flaviviridae, and reoviridae. in this review, we focus on therapeutic approaches for several of the more important tick-borne viruses from these 3 families. these viruses are crimean-congo hemorrhagic fever virus (cchf) and the newly discovered tick- ...201424907187
update and commentary on four emerging tick-borne infections: ehrlichia muris-like agent, borrelia miyamotoi, deer tick virus, heartland virus, and whether ticks play a role in transmission of bartonella henselae.emerging tick-borne infections continue to be observed in the united states and elsewhere. current information on the epidemiology, clinical and laboratory features, and treatment of infections due to ehrlichia muris-like agent, deer tick virus, borrelia miyamotoi sensu lato, and heartland virus was provided and critically reviewed. more research is needed to define the incidence and to understand the clinical and the laboratory features of these infections. there is also a growing need for the ...201525999230
transmission of heartland virus (bunyaviridae: phlebovirus) by experimentally infected amblyomma americanum (acari: ixodidae).heartland virus (hrtv; bunyaviridae: phlebovirus) is a recently described cause of human illness in the united states. after field studies conducted in 2012 implicated amblyomma americanum (l.) as a vector of hrtv, we initiated experiments to assess the vector competence of a. americanum larval and nymphal ticks were immersed in high-titered suspensions of hrtv, and then tested for virus at various intervals postimmersion. in a later trial larval ticks were immersed in hrtv, followed by engorgem ...201627330103
surveillance for heartland virus (bunyaviridae: phlebovirus) in missouri during 2013: first detection of virus in adults of amblyomma americanum (acari: ixodidae).during 2013, we collected and tested ticks for heartland virus (hrtv), a recently described human pathogen in the genus phlebovirus (bunyaviridae), from six sites in northwestern missouri. five sites were properties owned by hrtv patients, and the sixth was a conservation area that yielded virus in ticks during 2012. we collected 39,096 ticks representing five species; however, two species, amblyomma americanum (l.) (97.6%) and dermacentor variabilis (say) (2.3%), accounted for nearly all ticks ...201627032416
notes from the field: heartland virus disease - united states, 2012-2013.heartland virus is a newly identified phlebovirus that was first isolated from two northwestern missouri farmers hospitalized with fever, leukopenia, and thrombocytopenia in 2009. based on the patients' clinical findings and their reported exposures, the virus was suspected to be transmitted by ticks. after this discovery, cdc worked with state and local partners to define the ecology and modes of transmission of heartland virus, develop diagnostic assays, and identify additional cases to descri ...201424670929
arthropod-borne diseases: the camper's uninvited guests.arthropod-borne diseases are a major problem whenever outdoor activities bring arthropods and people into contact. the arthropods discussed here include arachnids (ticks) and insects. most arthropod bites and stings are minor, with the notable exception being bee-sting anaphylaxis. ticks cause the most disease transmission. key hard tick vectors include black-legged (ixodes), dog (dermacentor), and lone star (amblyomma) ticks, which transmit lyme and various rickettsial diseases. insect repellen ...201526350321
novel bunyavirus in domestic and captive farmed animals, minnesota, usa.we tested blood samples from domestic and captive farmed animals in minnesota, usa, to determine exposure to severe fever with thrombocytopenia syndrome virus and heartland-like virus. we found antibodies against virus nucleoproteins in 10%-18% of samples from cattle, sheep, goats, deer, and elk in 24 minnesota counties.201323966016
differential antagonism of human innate immune responses by tick-borne phlebovirus nonstructural proteins.in recent years, several newly discovered tick-borne viruses causing a wide spectrum of diseases in humans have been ascribed to the phlebovirus genus of the bunyaviridae family. the nonstructural protein (nss) of bunyaviruses is the main virulence factor and interferon (ifn) antagonist. we studied the molecular mechanisms of ifn antagonism employed by the nss proteins of human apathogenic uukuniemi virus (uukv) and those of heartland virus (hrtv) and severe fever with thrombocytopenia syndrome ...201728680969
animal models of emerging tick-borne phleboviruses: determining target cells in a lethal model of sftsv infection.the pathogenesis of clinical manifestations caused by newly emerging tick-borne phleboviruses [i.e., severe fever with thrombocytopenia syndrome virus (sftsv) and heartland virus (hrtv)], such as severe thrombocytopenia and lymphocytopenia, are not yet fully understood. in the present study, to establish an animal model mimicking the profile of fatal human cases, we examined the susceptibilities of adult mice from 12 strains, aged mice from two strains, and cynomolgus macaques to sftsv and/or hr ...201728194148
novel phleboviruses detected in ticks, greece.since 2009, when severe fever with thrombocytopenia syndrome virus and heartland virus have been identified and associated with disease in humans, the interest on tick-borne phleboviruses is increasing rapidly. the aim of the present study was to investigate the presence of tick-borne phleboviruses in greece and compare them with respective ones detected worldwide. ticks collected from goats and sheep in 60 sites of 13 regional units of greece were grouped in pools (1-3 ticks per pool) and teste ...201626935112
novel phlebovirus with zoonotic potential isolated from ticks, australia.recently discovered tick-borne phleboviruses have been associated with severe disease and death among persons in asia and the united states. we report the discovery of a novel tick phlebovirus in tasmania state, australia, that is closely related to those zoonotic viruses found in asia and north america.201424856477
severe fever with thrombocytopenia syndrome, an emerging tick-borne zoonosis.severe fever with thrombocytopenia syndrome (sfts) is an emerging haemorrhagic fever that was first described in rural areas of china. the causative agent, sfts virus (sftsv), is a novel phlebovirus in the bunyaviridae family. since the first report in 2010, sfts has been found in 11 provinces of china, with about 2500 reported cases, and an average case-fatality rate of 7·3%. the disease was also reported in japan and korea in 2012; heartland virus, another phlebovirus genetically closely relat ...201424837566
novel bunyavirus in domestic and captive farmed animals, minnesota, usa. 201424447797
the emergence of severe fever with thrombocytopenia syndrome virus.severe fever with thrombocytopenia syndrome (sfts) is a newly recognized hemorrhagic fever disease found throughout asia with a case fatality rate between 12% and 30%. since 2009, sfts has been reported in china throughout 14 chinese provinces. in addition, sfts has been recognized in south korea and japan with the first confirmed cases reported in 2012. a similar disease, caused by the closely related heartland virus, was also reported in the united states in 2009. sfts is caused by sfts virus, ...201728820686
heartland virus nss protein disrupts host defenses by blocking the tbk1 kinase-irf3 transcription factor interaction and signaling required for interferon induction.heartland virus (hrtv) is a pathogenic phlebovirus related to the severe fever with thrombocytopenia syndrome virus (sftsv), another phlebovirus causing life-threatening diseases in humans. previous findings have suggested that sftsv can antagonize the host interferon (ifn) system via viral nonstructural protein (nss)-mediated sequestration of antiviral signaling proteins into nss-induced inclusion bodies (ibs). however, whether and how hrtv counteracts the host innate immunity is unknown. here, ...201728848048
surveillance for tick-borne viruses near the location of a fatal human case of bourbon virus (family orthomyxoviridae: genus thogotovirus) in eastern kansas, 2015.bourbon virus (family orthomyxoviridae: genus thogotovirus) was first isolated from a human case-patient residing in bourbon county, kansas, who subsequently died. before becoming ill in late spring of 2014, the patient reported several tick bites. in response, we initiated tick surveillance in bourbon county and adjacent southern linn county during spring and summer of 2015. we collected 20,639 host-seeking ticks representing four species from 12 sites. amblyomma americanum (l.) (acari: ixodida ...201829365128
the postfusion structure of the heartland virus gc glycoprotein supports taxonomic separation of the bunyaviral families phenuiviridae and hantaviridae.heartland virus (hrtv) is an emerging human pathogen that belongs to the newly defined family phenuiviridae, order bunyavirales gn and gc are two viral surface glycoproteins encoded by the m segment and are required for early events during infection. hrtv delivers its genome into the cytoplasm by fusion of the viral envelope and endosomal membranes under low-ph conditions. here, we describe the crystal structure of hrtv gc in its postfusion conformation. the structure shows that gc displays a ty ...201829070692
heartland virus infection in hamsters deficient in type i interferon signaling: protracted disease course ameliorated by favipiravir.heartland virus (hrtv) is an emerging tick-borne virus (bunyaviridae, phlebovirus) that has caused sporadic cases of human disease in several central and mid-eastern states of america. animal models of hrtv disease are needed to gain insights into viral pathogenesis and advancing antiviral drug development. presence of clinical disease following hrtv challenge in hamsters deficient in stat2 function underscores the important role played by type i interferon-induced antiviral responses. however, ...201728865344
novel clinical and pathologic findings in a heartland virus-associated death.we describe an investigation into a heartland virus (hrtv)-associated death in tennessee with novel clinical and pathologic findings. hrtv can cause rapidly fatal, widely disseminated infection with multisystem organ failure in patients without substantial comorbidities. we identified viral antigen in multiple organ tissues where it was not detected previously.201727927857
heartland virus disease--united states, 2012-2013. 201425285350
heartland virus-associated death in tennessee.heartland virus (hrtv) is a tick-borne phlebovirus recently described in missouri that is associated with fever, leukopenia, and thrombocytopenia. the virus has also been detected in ambylomma americanum ticks.201424917656
experimental infection of white-tailed deer (odocoileus virginanus) with heartland virus.heartland virus (hrtv) is a phlebovirus suspected to be transmitted byamblyomma americanum, commonly known as the lone star tick, and reported to cause illness in humans, which is characterized by thrombocytopenia and leukopenia. heartland virus-reactive antibodies have been detected in a variety of wildlife species including white-tailed deer (wtd). to better understand the potential role of deer in the epidemiology of hrtv, we experimentally inoculated five wtd fawns with hrtv and monitored fo ...201829488458
zwiesel bat banyangvirus, a potentially zoonotic huaiyangshan banyangvirus (formerly known as sfts)-like banyangvirus in northern bats from germany.bats are reservoir hosts for several emerging and re-emerging viral pathogens causing morbidity and mortality in wildlife, animal stocks and humans. various viruses within the family phenuiviridae have been detected in bats, including the highly pathogenic rift valley fever virus and malsoor virus, a novel banyangvirus with close genetic relation to huaiyangshan banyangvirus (bhav)(former known as severe fever with thrombocytopenia syndrome virus, sftsv) and heartland virus (hrtv), both of which ...202031992832
heartland virus epidemiology, vector association, and disease potential.first identified in two missouri farmers exhibiting low white-blood-cell and platelet counts in 2009, heartland virus (hrtv) is genetically closely related to severe fever with thrombocytopenia syndrome virus (sftsv), a tick-borne phlebovirus producing similar symptoms in china, korea, and japan. field isolations of hrtv from several life stages of unfed, host-seeking amblyomma americanum, the lone star tick, implicated it as a putative vector capable of transstadial transmission. laboratory vec ...201830223439
heartland virus exposure in white-tailed deer in the southeastern united states, 2001-2015.heartland virus (hrtv) is a north american phlebovirus suspected to be transmitted by the lone star tick amblyomma americanum. white-tailed deer (wtd) have been shown to develop hrtv-neutralizing antibodies following experimental infection. to further define the geographic distribution of hrtv through retrospective sampling of wtd, sera from the wtd herd health serum archive at the southeastern cooperative wildlife disease study between 2001 and 2015 were analyzed using serum neutralization. of ...201830255829
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