characterization of dobrava virus: a hantavirus from slovenia, yugoslavia.small mammals were collected in natural foci of hemorrhagic fever with renal syndrome (hfrs) in slovenia, yugoslavia, and a hantavirus was isolated from the lungs of an apodemus flavicol lis captured in dobrava village. this new isolate, dobrava virus, was compared with representative strains of the hantavirus genus by serological and polymerase chain reaction-restriction fragment length polymorphism (pcr-rflp) methods. it was found by cross immunofluorescent and enzyme-linked immunosorbent assa ...19921360999
genetic and antigenic properties of dobrava virus: a unique member of the hantavirus genus, family bunyaviridae.we examined the genetic and antigenic properties of dobrava (dob) virus, a hantavirus associated with severe haemorrhagic fever with renal syndrome in europe. cloning and sequence analyses revealed the dob m segment to consist of 3644 nucleotides, with a coding capacity of 1134 amino acids in the virus complementary-sense rna (crna). seven potential asparagine-linked glycosylation sites were identified in the m segment gene product, one in the g2 and six in the g1 coding regions. the s segment i ...19957595387
belgrade virus, a cause of hemorrhagic fever with renal syndrome in the balkans, is closely related to dobrava virus of field mice.belgrade virus is a recently described hantavirus that causes severe hemorrhagic fever with renal syndrome (hfrs) in people living in various parts of the balkan peninsula. nucleotide sequencing of the g2-encoding region in the medium (m) segment of the viral genome, reverse transcribed and amplified by the polymerase chain reaction, revealed the belgrade virus to be substantially different from hantaan virus and other major serotypes of hantavirus but identical to dobrava virus, a virus isolate ...19938102632
phylogenetic analyses of virus isolates in the genus hantavirus, family bunyaviridae.we constructed a phylogenic tree by pairwise comparison of the deduced amino acid sequences encoded in the medium (m) genome segments of 13 hantaviruses. five distinct branches were identified, four of which are represented by hantaan, seoul, puumala, and prospect hill viruses. these groups corresponded to those previously established by serological and genetic means. in addition, we present sequence information for the m segment of thailand virus and demonstrate that it represents a unique, fif ...19948259656
dobrava virus as a new hantavirus: evidenced by comparative sequence analysis.dobrava virus, recently isolated from a yellow-neck mouse (apodemus flavicollis), captured in a northern slovenian village where severe cases of hemorrhagic fever with renal syndrome were recognized, was shown by serology and restriction enzyme digestion of pcr-amplified gene segments to be related to previously recognized hantaviruses. to investigate further the relationship of this new isolate to other hantaviruses, a portion of the medium (m) genome segment of dobrava virus was amplified by p ...19938487037
direct genetic detection of dobrava virus in greek and albanian patients with hemorrhagic fever with renal syndrome.blood samples were collected from an albanian and a greek patient with hemorrhagic fever with renal syndrome and tested by reverse transcriptase-polymerase chain reaction. the genetic detection assay amplified hantavirus-specific dna fragments from rna extracted from the blood of the patients; nucleotide sequence analysis revealed that the causative agent of the disease was dobrava virus. these findings suggest that dobrava virus (which was originally isolated from the lungs of an apodenws flavi ...19968699076
puumala and dobrava viruses cause hemorrhagic fever with renal syndrome in bosnia-herzegovina: evidence of highly cross-neutralizing antibody responses in early patient sera.hantavirus infection was diagnosed serologically by mu-capture igm and igg elisas in hemorrhagic fever with renal syndrome (hfrs) patients admitted to tuzla hospital, bosnia-herzegovina. the results indicated that more than one hantavirus caused the outbreak. to address the question of which hantavirus serotypes were involved, sequentially drawn sera were analyzed by focus reduction neutralization test (frnt) for antibodies against puumala, hantaan, dobrava, and seoul hantaviruses. the data reve ...19979298732
prevalence of serum antibodies to hantaviruses in northern sweden as measured by recombinant nucleocapsid enzyme-linked immunosorbent assay (elisa) based on recombinant nucleocapsid protein (rn delta) (aa 1-117) of hantaan, seoul, dobrava, sin nombre and puumala hantaviruses was used to determine the prevalence of antibodies among randomized and stratified individuals from northern sweden. in total, 137/1533 individuals (8.9%) had specific serum igg antibodies to puumala virus, the only hantavirus known to occur in the region. the prevalence of antibodies to puumala virus (8.9%) was determined to ...19979360248
retrospective serological and genetic study of the distribution of hantaviruses in greece.a retrospective serological and genetic study of hantaviruses responsible for hemorrhagic fever with renal syndrome (hfrs) in greece during the last 17 years is presented. fifty-one serum samples taken from 30 hfrs cases previously diagnosed by immunofluorescence assay were tested by elisa for igg (hantaan, dobrava, and puumala) and igm antibodies (hantaan and puumala). results were compatible with the majority of infections being related to hantaviruses carried by rodents of the subfamily murin ...19989661842
development of humoral cross-reactivity to the nucleocapsid protein of heterologous hantaviruses in nephropathia epidemica.a hantavirus infection is followed by a prominent antibody response to the viral nucleocapsid protein. antibodies from patients infected with one hantavirus cross-react to varying degrees with the nucleocapsid protein of other viruses of the genus. we studied the cross-reactivity in serially obtained blood samples from 17 patients with nephropathia epidemica, a european form of hemorrhagic fever with renal syndrome caused by puumala virus. recombinant truncated nucleocapsid protein (aa 1-117) of ...19989879922
genetic evidence of dobrava virus in apodemus agrarius in hungary.using nested polymerase chain reaction, we sequenced dobrava virus (dob) from the rodent apodemus agrarius in hungary. the samples we isolated group with dob samples previously isolated from a. flavicollis. this grouping may indicate host switching.199910341190
[increased travelling--increased risk of imported viruses. a review of the diagnostic capacity of the swedish institute for infectious disease control].the increase in global travel, especially by air, has facilitated the spread of infectious agents from one part of the world to another. returning travellers are often vectors for viral disease import to sweden. while dengue fever has been quite frequently diagnosed during the past five years, especially in travellers returning from thailand, only isolated cases of sandfly fever, japanese encephalitis and ross river fever have been seen. dobrava virus was recently shown to have caused a severe f ...199910405531
dobrava virus infection: serological diagnosis and cross-reactions to other hantaviruses.recent data have shown that dobrava (dob) hantavirus is the cause of severe haemorrhagic fever with renal syndrome (hfrs) in central and eastern europe. to determine whether serological assays need to be based on the homologous viral antigen rather than on closely related hantavirus antigens, acute and convalescent sera from patients with hfrs collected in former yugoslavia were examined for igm and igg to three hantavirus antigens; dob, hantaan (htn) and puumala (puu). focus reduction neutraliz ...199910471023
short report: simultaneous occurrence of dobrava, puumala, and tula hantaviruses in slovakia.the prevalence of antibody to hantaviruses in slovakia (serum panel n = 2,133) was lower in the western part (0.54%) and higher in the eastern part (1.91%) of the country and was found to be significantly enhanced in a group of forest workers from eastern slovakia (5.88%). one-third of the igm-negative convalescent phase sera from patients with hemorrhagic fever with renal syndrome exhibited antibodies reacting predominantly with puumala virus antigen, while two-thirds had antibodies directed ma ...199910497981
hantavirus dobrava infection with pulmonary manifestation.dobrava virus infection was diagnosed serologically by enzyme-linked immunosorbent and immunofluorescence assays. to determine which hantavirus serotype was involved, sera were analyzed by a focus reduction neutralization test. the clinical data indicated that only pulmonary manifestation was present. our data support the presence of dobrava virus infection outside the balkan region. in conclusion, a previously healthy adult with unexplained pulmonary perfusion failure should be investigated for ...199910691093
antigenic properties and diagnostic potential of recombinant dobrava virus nucleocapsid protein.dobrava hantavirus (dobv) causes severe hemorrhagic fever with renal syndrome in the balkan region and has been detected recently also in russia, estonia, and germany. dobv nucleocapsid protein (n) was produced in insect cells, using the baculovirus expression system (bac-dobv-n), and in e. coli as a truncated (aa 1-165) glutathione-s transferase fusion protein (dobv-dn-gst). the antigenic properties of bac-dobv-n were found identical to native dobv-n when examined by a panel of hantavirus-speci ...200010797384
hemorrhagic fever with renal syndrome in the dolenjska region of slovenia--a 10-year survey.this report describes the first investigation of clinical findings for a larger series of patients with hemorrhagic fever with renal syndrome (hfrs) who were infected with dobrava virus. from 1985 to 1995, 38 patients with serologically confirmed hfrs were hospitalized at the regional hospital in novo mesto in the dolenjska region of slovenia. on the basis of results of serological examination, 24 patients had dobrava virus infection, and 14 patients had puumala virus infection. complete clinica ...199910825051
dobrava hantavirus causes hemorrhagic fever with renal syndrome in central europe and is carried by two different apodemus mice central europe, hemorrhagic fevers with renal syndrome (hfrs) in humans are caused by the hantavirus species puumala (transmitted by voles) and a second, hantaan-related species (transmitted by mice). the second virus could be identified as dobrava virus. to date, 19 clinical cases of dobrava infection have been found in germany and slovakia. all patients exhibited a mild/moderate clinical course and no case fatality occurred. screening for infected rodents revealed that the striped field mou ...200111170053
isolation of dobrava virus from apodemus flavicollis in greece.dobrava virus (dobv) carried by apodemus flavicollis is the causative agent of severe hemorrhagic fever with renal syndrome (hfrs). dobv was isolated from an a. flavicollis mouse trapped in northeastern greece. this is the third dobv cell culture isolate in the world, clustering together with other greek dobv sequences from hfrs patients and rodents.200111376073
clinical characterization of dobrava hantavirus infections in germany.there is increasing evidence that dobrava (dobv) but not hantaan (htnv) hantavirus is a hemorrhagic fever with renal syndrome (hfrs) causing agent in central europe. however, only single clinical cases of hfrs due to acute dobv infection have been described so far. we report on three male patients from a non-endemic hantavirus focus in northern germany who suffered from mild to moderate hfrs strongly resembling nephropathia epidemica. serotyping by detection of hantavirus species-specific neutra ...200111393382
truncated hantavirus nucleocapsid proteins for serotyping hantaan, seoul, and dobrava hantavirus infections.truncated recombinant nucleocapsid proteins (rnps) of hantaan virus (htnv), seoul virus (seov), and dobrava virus (dobv) were expressed by a baculovirus system. the truncated rnps, which lacked 49 (rnp50) or 154 (rnp155) n-terminal amino acids of the nps of htnv, seov, and dobv, were able to differentiate htnv-, seov-, and dobv-specific immune sera. recombinant np50s retained higher reactivities than rnp155s and were proven useful for enzyme-linked immunosorbent assay (elisa). the elisas based o ...200111427545
dna vaccination with the hantaan virus m gene protects hamsters against three of four hfrs hantaviruses and elicits a high-titer neutralizing antibody response in rhesus monkeys.four hantaviruses-hantaan virus (htnv), seoul virus (seov), dobrava virus (dobv) and puumala virus-are known to cause hemorrhagic fever with renal syndrome (hfrs) in europe and asia. htnv causes the most severe form of hfrs (5 to 15% case-fatality rate) and afflicts tens of thousands of people annually. previously, we demonstrated that dna vaccination with a plasmid expressing the seov m gene elicited neutralizing antibodies and protected hamsters against infection with seov and htnv. here, we r ...200111507192
human immune response to puumala virus glycoproteins and nucleocapsid protein expressed in mammalian cells.puumala hantavirus (puuv) glycoproteins g1 and g2 and nucleocapsid protein (n) were expressed in bhk-21 cells by transfection of a plasmid producing a recombinant alphavirus replicon. coexpression of g1 and g2 from separate constructs seemed to be important for the optimal folding of the glycoproteins, as evaluated by a panel of mabs detecting conformational epitopes. to evaluate the human antibody response against recombinant g1, g2 and n, several panels of sera were tested by immunofluorescenc ...200111596100
hantavirus infections in greece--an update.hantaviruses are emerging viruses spread worldwide and cause hemorrhagic fever with renal syndrome (hfrs) or hantavirus pulmonary syndrome (hps). two pathogenic hantaviruses are present in greece: dobrava/belgrade virus (dobv) and puumala virus (puuv). the predominant one is dobv, carried in greece by the rodent apodemus flavicollis. most human infections are sporadic, but epidemic outbreaks were also described. the severity of the disease ranges from a mild or moderate form to severe and fatal ...200111599695
characteristics of puumala and dobrava infections in this study, two different hantaviruses, puumala virus (puuv) and dobrava virus (dobv), were demonstrated for the first time to coexist and cause hemorrhagic fever with renal syndrome (hfrs) in croatia. phylogenetic analysis showed some differences among the nucleotide sequences of puuv originating from dinara mountain, which was more closely related to austrian puuv than other croatian puuv from mala kapela mountain. more consistency was found among the croatian dobv. hfrs was verified in 85 ...200211857535
serological divergence of dobrava and saaremaa hantaviruses: evidence for two distinct order to investigate the serological relationship of dobrava hantavirus (dobv, originating from slovenia) and the dobrava-like saaremaa virus (saav, recently discovered in estonia) we analysed 37 human serum samples, 24 from estonia and 13 from the balkans, by focus reduction neutralization test (frnt). most of the estonian sera (19), including all sera from saaremaa island (12), reacted with higher frnt end-point titres to the local saav; the majority of them (15 and 11, respectively), with ...200211895097
double trouble: hemorrhagic fever with renal syndrome and leptospirosis.the clinical picture of hemorrhagic fever with renal syndrome can closely mimic that of unicteric leptospirosis and vice versa. this is the first description of dual infection with dobrava virus and leptospira and alteration of immune parameters in a croatian soldier.200212030403
cross-protection against challenge with puumala virus after immunization with nucleocapsid proteins from different hantaviruses.hantaviruses are rodent-borne agents that cause hemorrhagic fever with renal syndrome or hantavirus pulmonary syndrome in humans. the nucleocapsid protein (n) is relatively conserved among hantaviruses and highly immunogenic in both laboratory animals and humans, and it has been shown to induce efficient protective immunity in animal models. to investigate the ability of recombinant n (rn) from different hantaviruses to elicit cross-protection, we immunized bank voles with rn from puumala (puuv) ...200212050380
rodent host specificity of european hantaviruses: evidence of puumala virus interspecific order to investigate rodent host specificity of european hantaviruses, experimental infection of colonized and wild-trapped rodents was performed. in addition to the natural rodent reservoir, clethrionomys glareolus, puumala hantavirus (puuv) could infect colonized microtus agrestis and lemmus sibiricus, but not syrian hamsters or balb/c mice. neither c. glareolus, nor m. agrestis, could be readily infected by tula hantavirus (tulv). wild-trapped apodemus flavicollis and a. agrarius, the natu ...200212376967
hantaviruses in estonia.human serum samples collected from healthy individuals in 14 counties were screened by elisa in order to investigate the presence of hantavirus infections in estonia. out of 1,234 serum samples, 124 were found positive for hantavirus-specific igg and were subsequently serotyped by a focus reduction neutralization test. a total of 112 samples neutralized at least one of the examined hantaviruses-puumala (puuv), saaremaa (saav), dobrava (dobv), hantaan, and seoul viruses-and thereby, the focus red ...200212376968
phylogenetic evidence for host switching in the evolution of hantaviruses carried by apodemus mice.phylogenetic analysis of three hantaviruses: hantaan (htnv), dobrava (dobv), and the newly designated serotype/genotype saaremaa (saav) and their respective hosts, rodents of genus apodemus, reveals a discrepancy in the virus-host relationships. while all apodemus agrarius sequences from europe and the far east are monophyletic, saav (carried by the western subspecies of a. agrarius) shared the most recent ancestor with a. flavicollis-associated dobv virus, but not with htnv (carried by the east ...200212457975
genetic interaction between distinct dobrava hantavirus subtypes in apodemus agrarius and a. flavicollis in nature.dobrava virus (dobv) occurs in two different rodent species, apodemus flavicollis (dobv-af) and a. agrarius (dobv-aa). we sequenced the s and m genomic segments from sympatric dobv-af and dobv-aa strains which fell into two distinct genetic lineages. molecular phylogenetic analyses gave evidence for genetic reassortment between s and m segments of dobv-af and dobv-aa and indicated homologous recombination events in dobv evolution. dobv-af and dobv-aa are distinct but also subject to genetic exch ...200312477889
genetic characterization of new dobrava hantavirus isolate from greece.the first complete genome sequence of dobrava hantavirus isolated from yellow-necked mouse apodemus flavicollis trapped in the northeastern greece is described. the s, m, and l segments of the greek isolate of dobrava virus are 1673, 3635, and 6532 nucleotides (nt) long, respectively, and encode the nucleocapsid (n) protein of 429 amino acids (aa), glycoprotein precursor of 1135 aa, and the l protein of 2151 aa. n protein contains three cysteine residues conserved in all known hantaviruses, as w ...200312526053
diagnostic rapid tests for acute hantavirus infections: specific tests for hantaan, dobrava and puumala viruses versus a hantavirus combination test.hantaviruses infecting humans in eurasia include hantaan, seoul, puumala and the closely related dobrava and saaremaa viruses. these viruses are causative agents of hemorrhagic fever with renal syndrome (hfrs), which is recognized as a severe health care problem in several countries. diagnostics of hantavirus infections relies on serology, performed principally with enzyme immunoassay (eia) or immunofluorescence assay (ifa). we developed four 5-min immunochromatographic igm-antibody tests for di ...200312565162
serological analysis of hemorrhagic fever with renal syndrome (hfrs) patients in far eastern russia and identification of the causative hantavirus genotype.hemorrhagic fever with renal syndrome (hfrs) is endemic in east asia and europe. the disease is caused by several viruses belonging to the genus hantavirus, including the hantaan virus (htnv), seoul virus (seov), dobrava belgrade virus (dobv), and puumala virus (puuv). recently, htnv-related viruses, amur (amr) and far east (fe) genotypes were identified as causative agents of hfrs in far eastern russia. to investigate the epidemiology of hfrs and virus transmission, we collected sera from 17 ac ...200312898330
first molecular identification of human dobrava virus infection in central europe.viral rna was amplified by reverse transcription-pcr from a patient suffering from hemorrhagic fever with renal syndrome (hfrs) in germany. the virus strain could be assigned to the dobrava hantavirus (dobv). this is the first molecular identification of human infection by dobv in central europe and the first proof that a virus strain related to the dobv-aa lineage, carried by apodemus agrarius rodents, is able to cause hfrs.200415004109
[the biggest epidemic of hemorrhagic fever with renal syndrome in croatia].the largest outbreak of hemorrhagic fever with renal syndrome (hfrs) to date occurred in croatia in the year 2002. the epidemic started in winter, lasted throughout spring to summer months, ending not earlier than november.200315011458
[grading the severity of disease in patients with puumala or dobrava virus infections from 1995 to 2000 in croatia].the aim of our study was to evaluate the proposed croatian scale for grading the disease severity in patients with hemorrhagic fever with renal syndrome (hfrs). the aim was also to determine whether the infection with dobrava virus (dobv) in croatia was associated with a more severe illness than the infection with puumala virus (puuv).200315011460
[puumala and dobrava viruses in the northeastern and central regions of bosnia].bosnia and herzegovina has been known as a highly endemic region for hantavirus infections for more than 50 years. previous studies have shown that at least two different hantaviruses, the murine dobrava (dob) and avricoline puumala (puu) viruses, each carried by a different rodent species, have been circulating in the area. however, there is little information on rodent population density fluctuations in bosnia over the past years as well as on the ratio of puumala to dobrava infection in human ...200315011464
yeast-expressed hantavirus dobrava nucleocapsid protein induces a strong, long-lasting, and highly cross-reactive immune response in europe, dobrava virus (dobv) carried by the yellow-necked field mouse apodemus flavicollis is one of the hantaviruses that can cause severe hemorrhagic fever with renal syndrome in humans. for several hantaviruses, the nucleocapsid (n) protein has proven to be very immunogenic in humans and rodents and even can protect rodents against a virus challenge. to investigate the immunogenicity of dobv n protein, balb/c and c57bl/6 mice were immunized three times with a dobv recombinant n (rn) protei ...200415018668
identification of genetic evidence for dobrava virus spillover in rodents by nested reverse transcription (rt)-pcr and taqman rt-pcr.a survey of 158 rodents caught in the czech republic identified dobrava virus sequences closely related to that of the dobrava virus type strain in apodemus sylvaticus and mus musculus rodents. the identity of a. sylvaticus was unequivocally confirmed by random amplified polymorphic dna analysis. the data seem to indicate hantavirus spillover from apodemus flavicollis to other rodents.200515695684
detection of human hantavirus infections in europe certain hantaviruses are known to cause hemorrhagic fever with renal syndrome of different severity. the objective of the present investigation was to study the presence of hantavirus infections in lithuania.200515827873
development and evaluation of serological assays for detection of human hantavirus infections caused by sin nombre virus.the hantavirus cardiopulmonary syndrome (hcps) was first recognized in 1993 after a cluster of acute respiratory distress syndrome deaths in the southwestern of the united states. the major causative agent of hcps in north america is the sin nombre virus (snv) carried by the deer mouse peromyscus maniculatus. the first hcps case imported to europe was reported in 2002.200515911448
central european dobrava hantavirus isolate from a striped field mouse (apodemus agrarius).dobrava virus (dobv) is a hantavirus that causes hemorrhagic fever with renal syndrome (hfrs) in europe. it is hosted by at least two rodent species, apodemus flavicollis and a. agrarius. according to their natural hosts they form the distinct genetic lineages dobv-af and dobv-aa, respectively. we have now established a dobv isolate named slovakia (sk/aa) from an a. agrarius animal captured in slovakia. the complete s and m and partial l segment nucleotide sequences of the new isolate were deter ...200515956394
hemorrhagic fever with renal syndrome in the pomurje region of slovenia--an 18-year determine the etiology of hemorrhagic fever with renal syndrome (hfrs) in the north-eastern part of slovenia (pomurje region) together with demographic, epidemiological and clinical data on 25 patients from this region who were diagnosed and treated at the general hospital in murska sobota between 1986 and 2003.200516053195
[the epizootological and virological characteristics of a natural hantavirus infection focus in the subtropic zone of the krasnodarsk territory].a natural focus of hantavirus infection was detected and examined during the studies conducted in 2000-2002 around the sochi (the western spurs of the great caucasus ridge, which descended to the black sea (the krasnodar territory of russia). at least 4 rodent species, such as microtus majori, a. (s.) ponticus, a. agrarius, a. (s.) ciscaucasicus, were shown to participate in the circulation of hantaviruses. a comparative analysis of the nucleotide sequences of genomic s- and m-segments of hantav ...200516078428
phylogenetic evidence for the distinction of saaremaa and dobrava hantaviruses.dobrava virus (dobv) and saaremaa virus (saav) are two closely related hantaviruses carried by different rodent species. the distinction of these two viruses has been a matter of debate. while the phylogenies based on the viral m segment sequences were repeatedly showing monophyly of saav strains, some trees based on the s segment sequences were not, thus causing questions on the demarcation between these two viruses. in order to clarify this issue, the current collection of the virus s segment ...200516336658
hantavirus and arenavirus antibody prevalence in rodents and humans in trentino, northern italy.the spatial and temporal distribution of hantavirus and arenavirus antibody-positive wild rodents in trentino, italy, was studied using immunofluorescence assays (ifa) in two long-term sites trapped in 2000-2003, and six other sites trapped in 2002. the overall hantavirus seroprevalence in the bank voles, clethrionomys glareolus (n=229) screened for puumala virus (puuv) antibodies was 0.4%, and that for apodemus flavicollis mice (n=1416) screened for dobrava virus (dobv) antibodies was 0.2%. ant ...200616371172
dobrava, but not saaremaa, hantavirus is lethal and induces nitric oxide production in suckling mice.hantaviruses are the causative agents of hfrs and hcps (hemorrhagic fever with renal syndrome and hantavirus cardiopulmonary syndrome), two severe, and often fatal human diseases. mortality from hfrs varies between hantaviruses; hantaan and dobrava show the highest, seoul intermediate, and puumala low mortality. saaremaa, genetically closely related to dobrava, is also known to induce hfrs, with low or no mortality. in this study, mice were inoculated with dobrava and saaremaa viruses to test fo ...200616513381
saaremaa hantavirus should not be confused with its dangerous relative, dobrava virus. 200616597913
hantaviruses in serbia and montenegro.hantaviruses are endemic in the balkan peninsula. an outbreak of hemorrhagic fever with renal syndrome occurred in 2002 in serbia and montenegro. the epidemiologic characteristics and genetic relatedness of dobrava/belgrade virus strains responsible for most cases are described.200616707066
truncated recombinant dobrava hantavirus nucleocapsid proteins induce strong, long-lasting immune responses in mice.we describe the cloning and expression of dobrava hantavirus (dobv) nucleocapsid proteins and a truncated form consisting of the first 118 n-terminal amino acids, and the capacity of these e. coli icone 200-expressed recombinant proteins (rnp) to induce a protective immune response against dobv in mice. as an alternative carrier protein, the outer membrane protein a derived from klebsiella pneumoniae (rp40) has been coupled to different rnp constructs. all recombinant proteins were found to be h ...200616714853
development of novel immunoglobulin g (igg), iga, and igm enzyme immunoassays based on recombinant puumala and dobrava hantavirus nucleocapsid proteins.human infections with asian and european hantaviruses can result in hemorrhagic fever with renal syndromes of differing severities characterized by renal dysfunction and sometimes by pulmonary symptoms. for the serological detection of human infections by hantaviruses relevant for europe, we developed monoclonal antibody capture immunoglobulin g (igg) and iga enzyme-linked immunosorbent assays (elisas) based on yeast-expressed nucleocapsid proteins of puumala and dobrava hantaviruses. moreover, ...200617021245
detection of dobrava hantaviruses in apodemus agrarius mice in the transdanubian region of hungary.dobrava hantavirus (dobv) belongs to the genus hantavirus of the family bunyaviridae, and is carried by yellow necked and striped field mice (apodemus flavicollis and apodemus agrarius), respectively. the aim of this study was to detect and genetically characterize new dobv strains in rodents captured in the transdanubian region of hungary. rodent corpses were dissected and lung tissues were used for hantavirus detection by sybr green-based real-time rt-pcr using specific primers located in the ...200717524512
hantavirus disease outbreak in germany: limitations of routine serological diagnostics and clustering of virus sequences of human and rodent europe, hemorrhagic fever with renal syndrome results mainly from infection with puumala virus (puuv) or dobrava virus. for 31 patients from a hantavirus disease outbreak in lower bavaria, a district in southeast germany, serodiagnosis was undertaken by enzyme-linked immunosorbent assay, immunofluorescence assay, and immunoblot analysis. in a few of these cases, however, puuv-specific typing of antibodies by these standard assays failed and a virus neutralization assay under biosafety level 3 ...200717626170
case report: severe neurological manifestation of dobrava hantavirus europe infection with puumala or dobrava viruses causes hemorrhagic fever with renal syndrome (hfrs). in the course of hfrs, mild neurological symptoms such as headache, vertigo, and nausea are common. however, the data about the occurrence of severe, potentially life-threatening neurological manifestations are rather scarce. here, we present a case of hfrs with serologically proven dobrava virus infection complicated by epileptic seizures and hemiparesis due to focal encephalitis.200717935168
characterization of hemorrhagic fever with renal syndrome caused by hantaviruses, estonia.thirty cases of hemorrhagic fever with renal syndrome (hfrs) due to puumala virus (puuv), saaremaa virus (saav), and dobrava virus infection were confirmed in estonia. except for the levels of serum creatinine, no remarkable differences were found in the clinical course of hfrs caused by puuv and saav.200718217569
clinical course and laboratory parameters of the first dobrava-belgrade hantavirus infection imported to germany. 200818218336
dobrava virus rna load in patients who have hemorrhagic fever with renal asses the role of virus load in the pathogenesis of hemorrhagic fever with renal syndrome, the serum dobrava virus rna load in 46 patients was measured with a novel quantitative real-time reverse-transcriptase polymerase chain reaction assay and compared to the disease severity. the level of viremia, detected in 26 patients, ranged from 10(2)-10(8) copies/ml of serum. the patients with severe disease had, on average, higher viral rna loads than patients with a milder course of disease (6.15 v ...200818269319
truncated recombinant puumala virus nucleocapsid proteins protect mice against challenge in europe, puumala virus and dobrava virus are the major hantaviruses that cause hemorrhagic fever with renal syndrome in humans. as hantaviruses can cause diseases with high morbidity and mortality rates, and as to date there is no specific treatment, efforts are concentrated on the development of vaccines. in this study we characterized the immunogenicity of recombinant nucleocapsid proteins of puumala virus (puuv) linked to a carrier protein corresponding to the outer membrane protein a from ...200818355122
[discovery, clinical and etiological characteristic of hemorrhagic fever with renal syndrome in the subtropical zone of krasnodar region].twenty-six patients with hemorrhagic fever with renal syndrome (hfrs) were revealed as a result of serological examination of 582 patients with fever living around sochi town. etiologic role of dobrava virus subtype as the cause of hfrs was assessed by immunofluorescent and elisa assays, and neutralization test. the principal host of this virus and source of infection for humans is caucasian forest mouse apodemus ponticus. hfrs morbidity was sporadic and not dependent from patients' occupation a ...200818376466
hemorrhagic fever with renal syndrome caused by 2 lineages of dobrava hantavirus, russia.dobrava-belgrade virus (dobv) is a european hantavirus that causes hemorrhagic fever with renal syndrome (hfrs); case-fatality rates in balkan countries are as high as 12%. to determine causative agents, we examined 126 cases of dobv-associated hfrs in central and southern european russia. in central russia (lipetsk, voronezh, orel regions), outbreaks were caused by a dobv variant (dobv-aa) carried by apodemus agrarius. in southern russia (sochi district), where hfrs is endemic, hfrs cases were ...200818394280
high rates of molecular evolution in hantaviruses.hantaviruses are rodent-borne bunyaviruses that infect the arvicolinae, murinae, and sigmodontinae subfamilies of muridae. the rate of molecular evolution in the hantaviruses has been previously estimated at approximately 10(-7) nucleotide substitutions per site, per year (substitutions/site/year), based on the assumption of codivergence and hence shared divergence times with their rodent hosts. if substantiated, this would make the hantaviruses among the slowest evolving of all rna viruses. how ...200818417484
[the reactivity of sera from hemorrhagic fever in patients with renal syndromes to the recombination nucleotide proteins from european hantaviruses in hubei province].five yeast-expressed recombination nucleotide proteins of european hantaviruses were prepared as coated antigens to detect hantavirus-specific antibodies in sera from hemorrhagic fever with renal syndromes (hfrs) in hubei province, through elisa assay. the relativity among hantaviruses prevailing in different areas was investigated.200819040041
hantaviruses: an emerging public health threat in india? a review.the emerging viral diseases haemorrhagic fever with renal syndrome (hfrs) and hantavirus cardiopulmonary syndrome (hcps) are a cause of global concern as they are increasingly reported from newer regions of the world. the hantavirus species causing hfrs include hantaan virus,seoul virus, puumala virus, and dobrava-belgrade virus while sin nombre virus was responsible for the 1993 outbreak of hcps in the four corners region of the us. humans are accidental hosts and get infected by aerosols gener ...200819208975
the hantaviral load in tissues of naturally infected rodents.hantaviruses cause a lifelong and asymptomatic infection in naturally infected hosts as well as in experimentally infected rodents. understanding the ecology and pathogenesis of hantaviruses requires an interdisciplinary research approach, which links laboratory experiments with results gained from field studies. although several studies report hantavirus persistence and tissue infection patterns for experimentally infected rodents, field data is very limited. for this reason, the aim of our stu ...200919397875
the first established focus of hantavirus infection in poland, 2007.the first hantavirus infection outbreak in poland (with different seroetiology) was identified between august-december 2007. thirteen cases were reported in southeast poland: 12 cases in the carpathians bordering with northeast slovakia, mainly in the forested areas of the bieszczady mountains, and one case approximately 100-120 kilometres north from the others, in the adjacent sub-carpathian region. four additional cases of past infection were identified retrospectively, based on the presence o ...200919572481
[serological characteristics of hantaviruses from clinical specimens analyzed in 1998-2008 in the department of virology, public health institute, ostrava].in 1998 - 2008, serum samples from 464 patients, predominantly residents of the moravia-silesian region, were examined in the department of virology, public health institute in ostrava, using enzyme-linked immunosorbent assay (elisa) for the detection of specific anti-hantavirus antibodies. seropositivity was ascertained in 41 persons (8.8%). more patients tested seropositive against hantaan virus (24, i.e. 58.5%) than against puumala virus (13, i.e. 31.7%). four persons were reactive against bo ...200919750821
molecular diagnostics of hemorrhagic fever with renal syndrome during a dobrava virus infection outbreak in the european part of russia.a large outbreak of hemorrhagic fever with renal syndrome (hfrs) occurred in the winter of 2006-2007 in a region southeast of moscow in central european russia. of the 422 patients with hfrs investigated in this study, 58 patients were found to be infected by puumala virus, whereas as many as 364 were infected by dobrava-belgrade virus (dobv). early serum samples from 10 dobv-infected patients were used for nucleic acid amplification, which was successful for 5 patients. molecular analyses demon ...200919828747
genetic detection of dobrava/belgrade virus in a czech patient with haemorrhagic fever with renal the summer of 2008, a 15-year-old boy was hospitalized in a paediatric intensive care unit in the czech republic. laboratory diagnosis of hantavirus infection was established by serological and molecular methods. sequence and phylogenetic analyses showed that the causative strain was dobrava/belgrade virus, which is genetically closer to strains associated with apodemus flavicollis rodents.201019832712
co-circulation of three pathogenic hantaviruses: puumala, dobrava, and saaremaa in hungary.hantaviruses (bunyaviridae) cause hemorrhagic fever with renal syndrome (hfrs) in eurasia and hantavirus (cardio)pulmonary syndrome (hcps) in the americas. hfrs is caused by hantaan virus (htnv), seoul virus (seov), dobrava virus (dobv), saaremaa virus (saav), and puumala virus (puuv). of those, only htnv is not present in europe. in recent years, hantaviruses, described in other parts of europe, were also detected at various locations in hungary. to study the genetic properties of hungarian han ...200919856478
dobrava-belgrade virus spillover infections, germany.we present the molecular identification of apodemus agrarius (striped field mouse) as reservoir host of the dobrava-belgrade virus (dobv) lineage dobv-aa in 3 federal states of germany. phylogenetic analyses provided evidence for multiple spillover of dobv-aa to a. flavicollis, a crucial prerequisite for host switch and genetic reassortment.200919961690
comparison of the effects of puumala and dobrava viruses on early and long-term renal outcomes in patients with haemorrhagic fever with renal syndrome.the clinical course and outcome of patients with haemorrhagic fever with renal syndrome (hfrs) caused by puumala (puuv) and dobrava viruses (dobv) were analyzed and whether it left long-term consequences on kidney function after 10 years was evaluated.201020470304
genetic reassortment between high-virulent and low-virulent dobrava-belgrade virus strains.the tri-segmented rna genome of hantaviruses facilitates genetic reassortment by segment swapping when cells are co-infected with different virus strains. we found efficient in vitro reassortment between members of two different genetic lineages of the dobrava-belgrade virus species, the weakly virulent dobv-aa and highly virulent dobv-af. in all reassortants, s and l segments originated from the same parental strain, and only the m segment was exchanged. to identify functional differences betwe ...201020734125
dobrava-belgrade hantavirus infection mimics acute appendicitis.dobrava-belgrade hantavirus infection mimicked acute appendicitis in a patient suffering from hemorrhagic fever with renal syndrome in hungary. the 27-year-old man was admitted to the local hospital with severe abdominal pain localized mainly at the right lower quadrant of the abdomen and with fever, nausea, vomiting and bloody diarrhea. based on these findings supported by computerized tomography acute perforated appendicitis was suspected and an explorative laparatomy was performed, which did ...201021075678
specific humoral reaction of hemorrhagic fever with renal syndrome (hfrs) patients in china to recombinant nucleocapsid proteins from european hantaviruses.hemorrhagic fever with renal syndrome (hfrs) is endemic in east asia and europe. this study was initiated to investigate the reactivity of antibodies in sera of chinese hfrs patients with the recombinant nucleocapsid proteins (rnps) of hantaan virus (htnv), dobrava-belgrade virus (dobv), and puumala virus (puuv), which are the prevalent hantavirus strains in europe. forty-eight pairs of acute and convalescent sera were collected from hfrs patients in hubei, china (1985-2002) and tested by indire ...201121222012
hantavirus infection during a stay in a mountain hut in northern slovakia.hantaviruses in europe cause human hemorrhagic fever with renal syndrome (hfrs) with various degree of severity. the most severe form is caused by the dobrava/belgrade virus (dobv), associated with the rodent apodemus flavicollis. during the last decade cases of infection caused by dobv have been reported in central europe. the present study is a report on two czech patients with severe hfrs who were infected during their stay in a mountain hut in northern slovakia. the two patients, combined wi ...201121264871
genetic detection of dobrava/belgrade virus, bulgaria. 201121291615
procalcitonin in hantavirus hantavirus infections levels of serum leukocytes or c-reactive protein are usually elevated to levels found in serious bacterial infections. however, procalcitonin in patients infected with hantavirus has not yet been discussed in the literature. a total of 29 adult patients with hantavirus infection, 30 with sepsis, and 19 with tick-borne encephalitis were included in this observational retrospective study. the median procalcitonin level in patients with hantavirus infection was 0.53 µg/l (r ...201121344982
maporal virus as a surrogate for pathogenic new world hantaviruses and its inhibition by favipiravir.pathogenic hantaviruses geographically distributed in the old world cause haemorrhagic fever with renal syndrome (hfrs), whereas new world hantaviruses are the aetiological agents of hantavirus cardiopulmonary syndrome (hcps). ribavirin, a drug associated with toxicities, is presently indicated for treatment of hfrs, whereas treatment of the more frequently lethal hcps is limited to supportive care. because of the need for safe and effective antivirals to treat severe hantaviral infections, we e ...201121566265
detection of dobrava-belgrade hantavirus using recombinant-nucleocapsid-based enzyme-linked immunosorbent assay and sybr green-based real-time reverse transcriptase-polymerase chain reaction.dobrava (dobv) hantaviruses belong to the genus hantavirus, family bunyaviridae, and are carried by yellow-necked and striped field mice. the goal of this study was to detect dobv using serological and genetic methods in apodemus rodents in hungary and in northern croatia. during the study period, a total of 125 apodemus sp. (67 a. agrarius, 58 a. flavicollis) were tested for the presence of hantaviruses, and 21 rodents (17%) were positive by rrt-pcr and/or elisa. we conclude that the prevalence ...201121573689
seroprevalence study in forestry workers of a non-endemic region in eastern germany reveals infections by tula and dobrava-belgrade hantaviruses.highly endemic and outbreak regions for human hantavirus infections are located in the southern, southeastern, and western parts of germany. the dominant hantavirus is the bank vole transmitted puumala virus (puuv). in the eastern part of germany, previous investigations revealed tula virus (tulv) and dobrava-belgrade virus (dobv) infections in the respective rodent reservoirs. here, we describe a seroprevalence study in forestry workers from brandenburg, eastern germany, using igg elisa and imm ...201121611907
hla associated hemorrhagic fever with renal syndrom disease progression in slovenian patients.mhc class i and class ii genes regulate the balance between appropriate aggressive responses and invading pathogens while minimising the destruction of host tissue. several studies have shown that in hfrs patients the disease outcome is determined by a complex interaction between the virus, immunopathologic and human genetic factors. in slovenia the severity of the disease caused by puuv is significantly lower than that of hfrs due to dobv. we have determined 23 different hla-b and 12 different ...201121775516
Isolation of sochi virus from a fatal case of hantavirus disease with fulminant clinical course.Sochi virus, a novel genetic variant of Dobrava-Belgrade virus, was isolated in cell culture from a fulminant lethal case of hantavirus disease presenting with shock and combined kidney and lung failure. Sochi virus is transmitted to humans from host reservoir Apodemus ponticus and must be considered a life-threatening emerging agent.201222042875
application of truncated nucleocapsid protein (n) for serotyping elisa of murinae-associated hantavirus infection in rats.truncated recombinant nucleocapsid proteins (trns) that lack n-terminally located cross-reactive epitopes of four murinae rodent-associated hantaviruses, seoul virus (seov), thailand virus, hantaan virus (htnv) and dobrava-berglade virus, were produced by using a baculovirus expression system. elisa with the trns as antigens enabled serotyping of immune sera from rats experimentally inoculated with the corresponding hantaviruses as cut-off od values of 60% to those to whole n of htnv. the trn ba ...201121937858
identification of three novel ctl epitopes within nucleocapsid protein of hantaan virus.hantaan virus (htnv) is a member of the hantavirus genus that causes human hemorrhagic fever with renal syndrome (hfrs) in humans. the ctl response seems to play a key role in control of viral infection, but only a few htnv epitopes recognized by the ctls have been reported. herein, we screened a panel of overlapping peptides covering the htnv nucleocapsid protein by elispot assays for those that can elicit ifn-γ production in vitro. three novel cd8(+) ctl epitopes, n197-205 (ryrtavcgl), n245-25 ...201122111596
hemorrhagic fever with renal syndrome complicated by orchitis.hemorrhagic fever with renal syndrome (hfrs) is a disease caused by viruses of the family bunyaviridae, genus hantavirus. hfrs from dobrava virus (dobv) is a seldom reported disease in albania. clinically hfrs is manifested as mild, moderate, or severe. therefore, the number of cases of hantavirus' infection may be underestimated, and should be included in the differential diagnosis of many acute infections, hematologic diseases, acute abdominal diseases and renal diseases complicated by acute r ...201121847761
[the epidemiological, epizootological, and etiological characteristics of the 2006-2007 outbreak of hemorrhagic fever with renal syndrome in the tambov region].the findings suggest that there are natural foci of hantavirus infection in the tambov region. there is evidence that dobrava/belgrade hantavirus (dob-aa) was a leading etiological agent in the outbreak of the disease in the winter of 2006-2007. epidemiological analysis showed that the outbreak of hemorrhagic fever with renal syndrome (hfrs) afflicted the region during november to april, by reaching its peak in january (52.2%). among the patients with hfrs, rural dwellers were 91%. people were i ...201122359949
dobrava hantavirus infection complicated by panhypopituitarism, istanbul, turkey, 2010.we identified dobrava-belgrade virus infection in turkey (from a strain related to hantavirus strains from nearby countries) in a patient who had severe symptoms leading to panhypopituitarism, but no known risk for hantavirus. our findings emphasize the need for increased awareness of hantaviruses in the region and assessment of symptomatic persons without known risk factors for infection.201222709722
rodents and risk in the mekong delta of vietnam: seroprevalence of selected zoonotic viruses in rodents and the mekong delta in southern vietnam, rats are commonly traded in wet markets and sold live for food consumption. we investigated seroprevalence to selected groups of rodent-borne viruses among human populations with high levels of animal exposure and among co-located rodent populations. the indirect fluorescence antibody test (ifat) was used to determine seropositivity to representative reference strains of hantaviruses (dobrava virus [dobv], seoul virus [seov]), cowpox virus, arenaviruses ( ...025629782
survey for hantaviruses, tick-borne encephalitis virus, and rickettsia spp. in small rodents in croatia, several rodent- and vector-borne agents are endemic and of medical importance. in this study, we investigated hantaviruses and, for the first time, tick-borne encephalitis virus (tbev) and rickettsia spp. in small wild rodents from two different sites (mountainous and lowland region) in croatia. in total, 194 transudate and tissue samples from 170 rodents (a. flavicollis, n=115; a. agrarius, n=2; myodes glareolus, n=53) were tested for antibodies by indirect immunofluorescence assays ...201424866325
clinical characterization of two severe cases of hemorrhagic fever with renal syndrome (hfrs) caused by hantaviruses puumala and dobrava-belgrade genotype sochi.hantavirus disease belongs to the emerging infections. the clinical picture and severity of infections differ between hantavirus species and may even vary between hantavirus genotypes. the mechanisms that lead to the broad variance of severity in infected patients are not completely understood. host- and virus-specific factors are considered.201627842513
multiple co-infections of rodents with hantaviruses, leptospira, and babesia in croatia.hantaviruses, leptospira spp., and babesia spp. are rodent-borne pathogens present worldwide. we studied multiple co-infections of small rodents in croatia with all three pathogens. twenty-eight apodemus flavicollis and 16 myodes glareolus were tested for the presence of hantavirus rna by real-time rt-pcr, leptospira strains by renoculture method and babesia dna by pcr. anti-hantavirus antibodies and anti-leptospira antibodies were detected by serological methods. very high infection rates with ...201222217170
multiple infections of rodents with zoonotic pathogens in austria.rodents are important reservoirs for a large number of zoonotic pathogens. we examined the occurrence of 11 viral, bacterial, and parasitic agents in rodent populations in austria, including three different hantaviruses, lymphocytic choriomeningitis virus, orthopox virus, leptospira spp., borrelia spp., rickettsia spp., bartonella spp., coxiella burnetii, and toxoplasma gondii. in 2008, 110 rodents of four species (40 clethrionomys glareolus, 29 apodemus flavicollis, 26 apodemus sylvaticus, and ...201424915446
in search for factors that drive hantavirus europe, hantaviruses (bunyaviridae) are small mammal-associated zoonotic and emerging pathogens that can cause hemorrhagic fever with renal syndrome (hfrs). puumala virus, the main etiological agent carried by the bank vole myodes glareolus is responsible for a mild form of hfrs while dobrava virus induces less frequent but more severe cases of hfrs. since 2000 in europe, more than 3000 cases of hfrs have been recorded, in average, each year, which is nearly double compared to the previous de ...201222934002
antiviral therapy and prevention against hantavirus infections.hantaviruses are emerging zoonoses hosted by small mammals. in humans, they cause two diseases. hemorrhagic fever with renal syndrome is mainly caused by dobrava-belgrade virus, puumala virus, seoul virus and hantaan virus in asia and europe. on the other hand, the most important causes of hantavirus cardiopulmonary syndrome are sin nombre virus and andes virus in americas. ribavirin yet remains the only licensed drug against the hantavirus infections, but its sufficient antiviral activity remai ...201728105849
hantavirus infections by puumala or dobrava-belgrade virus in pregnant women.hantavirus infection in humans usually occurs via inhalation of infectious aerosolized excreta of rodents. horizontal human-to-human transmission was reported only for the highly virulent andes virus. the likelihood of vertical transmission and the clinical outcome of hantavirus infections in pregnancy is still unpredictable.201222877560
serum levels of metalloproteinases and their inhibitors during infection with pathogens having integrin receptor-mediated cellular entry.matrix metalloproteinases (mmps) are a family of proteolytic enzymes with numerous roles in the normal immune response to infection. however, excess mmp activity following infection may lead to immunopathological processes that cause tissue damage. their activity in normal tissues is subject to tight control, which is regulated by its specific endogenous tissue inhibitors (timps). it is known that mmps bind to cell surface proteins (e.g. integrins) and that such interactions can have modulatory ...201222831170
clinical aspects of hantavirus infections in bulgaria.hantaviruses cause two distinct human diseases: hemorrhagic fever with renal syndrome (hfrs) in asia and europe and hantavirus pulmonary syndrome (hps) in america. in europe, mainly puumala, dobrava and seoul viruses cause hfrs. a total of 23 cases of hfrs were detected in bulgaria over a 2‑year period 2013-2014. the aim of the study was to present epidemiology, clinical manifestations and laboratory findings of these patients.201728229289
population dynamics of wild rodents induce stochastic fadeouts of a zoonotic pathogen.stochastic processes play an important role in the infectious disease dynamics of wildlife, especially in species subject to large population oscillations. here, we study the case of a free ranging population of yellow-necked mice (apodemus flavicollis) in northern italy, where circulation of dobrava-belgrade hantavirus (dobv) has been detected intermittently since 2001, until an outbreak emerged in 2010. we analysed the transmission dynamics of the recent outbreak using a computational model th ...201728217934
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