biotin-labeled antigen: a novel approach for detection of puumala virus-specific igm.a novel enzyme-linked immunosorbent assay, bla igm-elisa, based on baculovirus-expressed puumala (puu) virus nucleocapsid protein, was developed for rapid diagnosis of nephropathia epidemica. the recombinant antigen (bac-puu-n) was purified to homogeneity by hplc and conjugated to biotin. the biotin-streptavidin system, in combination with the mu-capture technique, rendered the bla igm-elisa a sensitivity similar to or higher than that of puu virus igm mu-capture elisa based on native antigen. t ...19968910652
[hantavirus infection in spain: seroepidemiologic study in the province of soria].the aim of the present was to study the seroprevalence of hantavirus infection in the province of soria, spain.19968948928
pulmonary involvement in nephropathia epidemica: radiological findings and their clinical correlations.nephropathia epidemica (ne) is a hemorrhagic fever with renal syndrome (hfrs) normally taking a benign clinical course. the etiologic agent, puumala hantavirus is genetically closely related to sin nombre virus, which causes a frequently lethal febrile syndrome with pulmonary involvement (hantavirus pulmonary syndrome, hps). hps is characterized by acute respiratory distress, non-cardiogenic pulmonary edema and severe and hypotension, but usually no significant renal involvement. pulmonary invol ...19968982552
hantavirus antigen detection in kidney biopsies from patients with nephropathia epidemica.renal biopsies collected from ten patients with serologically confirmed puumalavirus (puuv) infection in the acute stage with renal dysfunction who lived in the same puuv endemic area in the netherlands, were studied histologically, immuno-histochemically and subsequently examined for the presence of viral antigen by immunoperoxidase staining. interstitial hemorrhages and deposition of igm, complement component c3 and fibrin along the basal side of the tubular epithelial cells, were found in puu ...19968982553
[a system of immunoenzyme analysis using biotinylated monoclonal antibodies for typing hantavirus antigens].enzyme immunoassay with biotin-labeled monoclonal antibodies to puumala virus was used for typing hantavirus antigens. the system is type-specific, that is, it detects puumala virus only, which was demonstrated by typing 9 hantavirus antigens in infected vero e5 cells and by epizootological analysis of an hfrs outbreak in the yegoryevsk district of the moscow region in november-december 1995. the suggested system may be used as an element of eia screening of natural samples in analysis of the sc ...19968999683
ocular characteristics in nephropathia epidemica or puumala virus infection.we documented the largest series so far concerning the ocular characteristics of nephropathia epidemica.19969017055
rapid and specific detection of sin nombre virus antibodies in patients with hantavirus pulmonary syndrome by a strip immunoblot assay suitable for field develop a rapid antibody test for sin nombre hantavirus (snv) infection for diagnosis of hantavirus pulmonary syndrome (hps) in field settings where advanced instrumentation is not available, a strip immunoblot assay bearing four immobilized antigens for snv and a recombinant nucleocapsid protein antigen of seoul hantavirus (seov) was prepared. the snv antigens included a full-length recombinant-expressed nucleocapsid (n) protein (rn), a recombinant-expressed g1 protein (residues 35 to 117), ...19979041397
phage-displayed peptide targeting on the puumala hantavirus neutralization site.we have selected ligands for puumala hantavirus, the causative agent of nephropathia epidemica, from a seven-amino-acid peptide library flanked by cysteines and displayed on a filamentous phage. to direct the selection to areas on the virus particle which are essential for infection, phages were competitively eluted with neutralizing monoclonal antibodies specific for the viral glycoproteins. the selected phage populations were specific for the same sites as the antibodies and mimicked their fun ...19979094664
intraocular pressure changes in nephropathia epidemica. a prospective study of 37 patients with acute systemic puumala virus infection.nephropathia epidemica is a zoonose in the group of hemorrhagic fevers with renal syndrome and is caused by puumala virus in hantavirus genus. the purpose of this study is to find out how the intraocular pressure (iop) is affected by the acute phase of this disease and how it relates to the previous case reports on angleclosure glaucoma attacks.19959098282
puumala hantavirus genome in patients with nephropathia epidemica: correlation of pcr positivity with hla haplotype and link to viral sequences in local rodents.reverse transcription-pcr was used to analyze specimens from 20 finnish nephropathia epidemica (ne) patients hospitalized during the period from october 1994 to january 1995. blood and/or urine sediment specimens from seven patients were found to be positive for the genome sequences of puumala hantavirus (puu). pcr positivity of the specimens from the patients correlated well with the hla-drb1*0301 and hla b8 alleles, which previously were shown to associate with severe courses of ne. genetic an ...19979114386
single amino acid substitutions in puumala virus envelope glycoproteins g1 and g2 eliminate important neutralization epitopes.two monoclonal antibody escape virus mutants (mars), rescued from a human mab to glycoprotein 2 (g2) and a bank vole monoclonal antibody (mab) directed to glycoprotein 1 (g1) of puumala virus, strain sotkamo, were produced by using a combination of neutralization tests and antigen detection. the mars and the original virus were analyzed by nucleotide sequencing and the responsible mutations were defined and characterized. the g1 mutation was found to constitute an a to t nucleotide substitution, ...19979140197
a major antigenic domain of hantaviruses is located on the aminoproximal site of the viral nucleocapsid protein.hantavirus nucleocapsid protein has recently been shown to be an immunodominant antigen in hemorrhagic with renal syndrome (hfrs) inducing an early and long-lasting immune response. recombinant proteins representing various regions of the nucleocapsid proteins as well as segments of the g1 and the g2 glycoproteins of hantavirus strains cg18-20 (puumala serotype) and hantaan 76-118 have been expressed in e. coli. the antigenicity of these proteins was tested in enzyme immunoassays and immunoblots ...19979208453
high prevalence of hantavirus antibodies in bank voles (clethrionomys glareolus) captured in the vicinity of households afflicted with nephropathia epidemica.puumala virus, the causative agent of nephropathia epidemica (ne), occurs endemically in europe and is spread mainly by the bank vole (clethrionomys glareolus). in the vicinity of each of four households afflicted with ne, we studied rodents with regard to population density and prevalence of puumala virus-specific antibodies. for each case area, a control area was randomly selected 10 km away, without regard to the presence of human settlement. during 6,000 trap nights, 328 rodents were caught, ...19979230802
increased plasma levels of soluble cd23 in haemorrhagic fever with renal syndrome; relation to virus-specific 15 consecutive patients hospitalized with nephropathia epidemica, a european form of haemorrhagic fever with renal syndrome (hfrs) caused by puumala virus, plasma concentrations of soluble cd23 (scd23) and puumala virus-specific ige were determined. in the acute phase of illness, 11/15 patients had increased scd23 levels (> 91 u/ml), whereas in convalescence, values of 8/10 patients were normalized. maximal scd23 values were correlated to maximal concentrations of puumala virus-specific serum ...19979276532
baculovirus expression of a human g2-specific, neutralizing igg monoclonal antibody to puumala virus.we amplified by polymerase chain reaction the heavy- and light-chain antibody genes of a human hybridoma secreting a neutralizing, igg monoclonal antibody to the g2 protein of puumala virus. the heavy- and light-chain genes were cloned and sequenced and the deduced amino acids were aligned with those of other human antibodies to identify the constant and variable regions. the genes were cloned into the baculovirus plasmid transfer vector pacuw51 such that the heavy-chain and light-chain genes we ...19979281505
the first human isolate of puumala virus in scandinavia as cultured from phytohemagglutinin stimulated leucocytes.a virus isolate was recovered from blood leucocytes of a patient with nephropathia epidemica (ne). leucocytes were isolated from edta-blood by dextran sedimentation and cultured on monolayers of vero e6 cells in the presence of phytohemagglutinin (pha) in roller tubes during the first 72 hours of incubation followed by rolling culture for three weeks in total. thereafter the first subculture was done in a plastic flask and afterward at at least 6 week intervals. antigen was first detected after ...19979334926
puumala virus and two genetic variants of tula virus are present in austrian rodents.puumala and tula viruses are hantaviruses found in europe and are associated with the rodents clethrionomys glareolus and microtus arvalis, respectively. puumala virus is associated with the human disease nephropathia epidemica. in austria, ten clinically diagnosed cases of nephropathia epidemica, presumably caused by puumala virus infection, have been reported but not virologically confirmed [leschinskaya et al., 1991; aberle et al., 1996]. to identify the hantaviruses that are present in austr ...19979334930
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
cell culture adaptation of puumala hantavirus changes the infectivity for its natural reservoir, clethrionomys glareolus, and leads to accumulation of mutants with altered genomic rna s segment.this paper reports the establishment of a model for hantavirus host adaptation. wild-type (wt) (bank vole-passaged) and vero e6 cell-cultured variants of puumala virus strain kazan were analyzed for their virologic and genetic properties. the wt variant was well adapted for reproduction in bank voles but not in cell culture, while the vero e6 strains replicated to much higher efficiency in cell culture but did not reproducibly infect bank voles. comparison of the consensus sequences of the respe ...19979371614
sequence analysis of the puumala hantavirus sotkamo strain l segment.sequence of the puumala virus (puu) sotkamo strain l segment is provided, completing the total genome of this prototype puu virus strain. the l segment is 6530 nucleotides long and it can encode 2156 amino-acids-long l protein, rna-dependent rna polymerase. the strain sotkamo, originally isolated in finland, showed for the l genome segment nucleotide (84.6%) and amino acid (97.3%) homology to a previously sequenced puu russian isolate, strain bashkiria/cg1820 (b1820) and the l genome segment app ...19979381791
evaluation of serological methods for diagnosis of puumala hantavirus infection (nephropathia epidemica).nephropathia epidemica (ne), puumala (puu) virus infection, is a febrile disease which is commonly associated with acute renal impairment. to differentiate ne from other acute febrile illnesses, a rapid and reliable serological diagnosis is important, and a number of different protocols have recently been introduced. in the present report we describe a comparative evaluation of six puu virus immunoglobulin m (igm) and seven igg enzyme-linked immunosorbent assay (elisa) protocols based on native, ...19979399531
severe thrombocytopenia and response to corticosteroids in a case of nephropathia epidemica.nine days after working in the woods, a previously healthy 32-year-old man fell seriously ill. his symptoms included high fever, chills, diffuse myalgia, severe headache, and back pain. on the fifth day of onset of symptoms, blood tests showed creatinine levels of 5.4 mg/dl accompanied by marked proteinuria. after admission to the hospital, a diagnosis of nephropathia epidemica (ne) caused by puumala virus was made using solid-phase enzyme-linked immunosorbent assay (elisa). the patient graduall ...19989428461
association of hla b27 with benign clinical course of nephropathia epidemica caused by puumala hantavirus.both the severe course of nephropathia epidemica (ne) caused by puumala hantavirus, and the fast progression of human immunodeficiency virus (hiv) disease, are associated with the hla b8 drb1*0301 haplotype. as hla b27, on the contrary, is associated with the slow progression of hiv disease, we wanted to test whether the same is true for ne. only six (8%) ne patients, half the figure expected, had the hla b27 allele in 74 randomly selected hospital-treated patients. all six had a benign overall ...19989519867
human recombinant puumala virus antibodies: cross-reaction with other hantaviruses and use in diagnostics.a panel of seven human monoclonal fabs against puumala virus (puu) nucleocapsid protein (n) was obtained by panning an antibody phage-display library prepared from the spleen of a puu-immune individual. three antibodies reacted in immunoblotting and cross-reacted strongly with tula and sin nombre virus recombinant n proteins. these antibodies mapped to the amino terminus of the n protein. one puu glycoprotein 2 (g2)-specific fab obtained against a novel epitope (g2c) cross-reacted with khabarovs ...19989568958
chimaeric hbv core particles carrying a defined segment of puumala hantavirus nucleocapsid protein evoke protective immunity in an animal model.hantaviruses are rodent-born agents which are pathogenic in humans causing haemorrhagic fever with renal syndrome or hantavirus pulmonary syndrome. to induce a protective immunity against a european hantavirus (puumala) we constructed chimaeric hepatitis b virus (hbv) core particles carrying defined fragments of the puumala virus nucleocapsid protein. after immunisation of bank voles, the natural host of puumala virus, with core particles possessing an insertion of the n-terminal part of puumala ...19989607042
haemorrhagic fever with renal syndrome caused by puumala virus: evaluation of the risk for cataract formation. 19989614533
prevalence of antibodies specific to puumala virus among farmers in sweden.the puumala virus is the causative agent of nephropathia epidemica, a european form of hemorrhagic fever with a renal syndrome. from its reservoir in bank voles, the virus is spread by airborne transmission to humans. occupational risks for the acquisition of nephropathia epidemica are not well defined. the prevalence of serum antibodies to puumala virus was determined for swedish farmers. from a comparison of the prevalence among farmers from various parts of the country, the assumption that pu ...19989630057
evaluation of puumala virus igg and igm enzyme immunoassays based on recombinant baculovirus-expressed nucleocapsid protein for early nephropathia epidemica diagnosis.puumala virus (puu), a member of hantavirus genus, is the causative agent of nephropathia epidemica (ne), a milder form of hemorrhagic fever with renal syndrome (hfrs). rapid diagnosis is essential for clinical management of ne.19989646005
fluorescein iris angiography in the febrile phase of puumala virus infection (hemorrhagic fever with renal syndrome) 19989716346
human dobrava hantavirus infections in estonia.outbreaks of severe hemorrhagic fever with renal syndrome (hfrs) caused by dobrava hantavirus (dob) have been reported in albania, greece, and bosnia-herzegovina. a seroepidemiologic study conducted by the authors in estonia provided the first evidence of human dob infection in a baltic country. hantavirus infection was first confirmed in estonia in 1986 and believed related to puumala hantavirus (puu). to enable precise serotyping, serum samples were collected from 1728 healthy people in 11 ...19989717928
hantavirus seropositivity in israeli patients with renal failure.the hantavirus is known to cause hemorraghic fever with renal syndrome (hfrs), which is widely spread in europe and asia. several reports have shown an association of hantavirus antibody titers and the occurrence of renal dysfunction. from these observations, it appears that the virus is widely distributed, and different strains prevail in various areas. in the present work we studied 81 patients with end-stage renal-failure under hemodialysis (hd) treatment, 55 with mild to moderate renal failu ...19989765032
hemorrhagic fever (puumala virus infection) with ocular involvement.puumala virus infection (nephropathia epidemica) is a disease in the group of hemorrhagic fevers with renal syndrome causing ocular manifestations, e.g. transient myopia and changes in intraocular pressure.19989782434
isolation and characterization of puumala hantavirus from norway: evidence for a distinct phylogenetic sublineage.puumala (puu) hantavirus is the aetiological agent of nephropathia epidemica (ne), a mild form of haemorrhagic fever with renal syndrome, which occurs in fennoscandia, central europe and russia. in norway, ne-like disease has been reported since 1946 and about 50 cases are diagnosed annually; however, the causative agent has not been characterized. in this study, a virus originating from bank voles (clethrionomys glareolus) trapped near the town of eidsvoll (akershus county) was isolated and pas ...19989820135
a minority of seropositive wild bank voles (clethrionomys glareolus) show evidence of current puumala virus voles (clethrionomys glareolus) serve as the reservoir for puumala (puu) virus, the aetiologic agent of nephropathia epidemica. the animals are believed to be persistently infected and the occurrence of serum antibodies is usually taken as an evidence of active infection. we found serum antibodies to puu virus in 42 of 299 wild bank voles captured in a puu virus endemic area. puu virus rna was demonstrated in lung specimens of 11 of these 42 animals and in 2 of them antigen was also found. ...19989825795
stable expression of nucleocapsid proteins of puumala and hantaan virus in mammalian cells.the development of an in vitro-system for the stable expression and the analysis of native hantavirus proteins using hantaviral cdna is of particular interest. as a first step the expression of the hantavirus nucleocapsid (n) proteins in mammalian cells was studied in more detail. the cdna of the s-rna segment of puumala virus strain cg-1820 and hantaan virus strain 76-118 was used for the construction of eucaryotic expression vectors that allow the generation and selection of mammalian cells ha ...19989857992
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
[diseases caused by hantaviruses].hantaviruses are rna viruses that belong to the genus hantavirus, family bunyaviridae. the main reservoir of hantaviruses are rodents. humans become infected by inhaling particles of dust contaminated with faeces of rodents, that are found in europe and asia hantaviruses named: hantaan, seoul and dobrava-belgrade causing haemorrhagic fever with renal syndrome (hfrs) are prevalent. typical clinical picture of hfrs consists of renal insufficiency (primarily anuria and then polyuria with disturbanc ...19989919918
high-producer allele of tumour necrosis factor-alpha is part of the susceptibility mhc haplotype in severe puumala virus-induced nephropathia epidemica.the biallelic polymorphisms in the tumour necrosis factor-alpha (tnf-alpha) gene promoter region were studied in patients with nephropathia epidemica (ne). the rarer tnf2 allele, associated with a high tnf-alpha producer phenotype, was more frequently found in hospitalized ne patients (42%) than in healthy controls (15%; p=0.0064). the putative role of tnf2 as an independent risk factor for ne is discussed.199810066063
genetic diversities of hantaviruses among rodents in hokkaido, japan and far east russia.seroepizootiologic surveys among wild rodents were carried out in japan and far east russia in 1995 and 1996. seropositive animals were only identified in clethrionomys rufocanus (23/134) in hokkaido, japan. on the other hand, seropositives were identified in c. rufocanus (1/8), apodemus agrarius (2/66), apodemus spp. (2/26) and microtus fortis (3/22) in vladivostok, far east russia. total rna was isolated from lungs of seropositive animals and the s genome segments were amplified by pcr, cloned ...199910082393
hbv core particles allow the insertion and surface exposure of the entire potentially protective region of puumala hantavirus nucleocapsid protein.core particles of the hepatitis b virus (hbv) potentiate the immune response against foreign epitopes presented on their surface. potential insertion sites in the monomeric subunit of the hbv core protein were previously identified at the n- and c-terminus and in the immunodominant c/e1 region. in a c-terminally truncated core protein these sites were used to introduce the entire 120 amino acid (aa)-long potentially immunoprotective region of the hantavirus (serotype puumala) nucleocapsid protei ...199910223335
polymerase chain reaction detection of puumala virus rna in formaldehyde-fixed biopsy material.infections with hantaviruses, mainly clethrionomys-derived puumala viruses, are known causes of acute renal failure [hemorrhagic fever with renal syndrome (hfrs)] in western europe. laboratory diagnosis is primarily based on serology. at the time of clinical symptoms, viral rna can hardly be detected in the blood or urine, indicating that polymerase chain reaction (pcr) is of little diagnostic value for these infections. biopsy material is usually formaldehyde-fixed and, thus, regarded as poor q ...199910231472
puumala virus infections in finland: increased occupational risk for farmers.puumala hantavirus, transmitted by bank voles (clethrionomys glareolus), causes a mild-type hemorrhagic fever with renal syndrome. the disease is common in finland and is considered an occupational hazard for farmers, but the actual risk has not been assessed by analytical studies. data on 5,132 serologically confirmed puumala virus infections during 1989-1994 were analyzed, and cases among farmers and the population living in similar conditions were compared. the farmers contracted the disease ...199910369509
pathogenesis of puumala and other hantavirus infections.hantaviruses are rodent/insectivore-borne negative-stranded rna viruses which belong to the bunyaviridae family. they do not cause any symptomatic disease in their adult carrier rodents, but in humans they are aetiologic agents of haemorrhagic fever with renal syndrome (hfrs) and hantavirus pulmonary syndrome (hps), both associated with a significant mortality. in cell culture hantaviruses do not cause cytopathic effects and the mechanisms of disease in man are not well understood. increased cap ...199810398496
haemolytic-uraemic syndrome caused by vero toxin-producing escherichia coli serotype rough: k-: h49.the first case of haemolytic-uraemic syndrome (hus) caused by vero toxin-producing escherichia coli (vtec) which belonged to a novel serotype, rough: k-: h49, is reported. the case was initially diagnosed as nephropathia epidemica caused by puumala virus, but the subsequent diagnosis of hus caused by vtec was made after bacteriological investigation. the strain isolated fermented sorbitol produced vt2 toxin but not enterohaemolysin, nor did it carry the eaea gene. in vtec strains, the o antigen, ...199910447322
nephropathia epidemica and puumala virus in study the epidemiology of hantavirus infections in austria, 1215 humans and 596 rodents of different species were tested for the presence of antibodies against puumala and hantaan virus. direct virus identification by polymerase chain reaction in lung tissue of serologically positive rodents was performed to verify antibody results and to determine the genetic identity of viral rna by phylogenetic analysis of a part of the hantavirus m segment. for 32 of the 37 cases of nephropathia epidemica ...199910482022
new chimaeric hepatitis b virus core particles carrying hantavirus (serotype puumala) epitopes: immunogenicity and protection against virus challenge.virus-like particles generated by the heterologous expression of virus structural proteins are able to potentiate the immunogenicity of foreign epitopes presented on their surface. in recent years epitopes of various origin have been inserted into the core antigen of hepatitis b virus (hbv) allowing the formation of chimaeric hbv core particles. chimaeric core particles carrying the 45 n-terminal amino acids of the puumala hantavirus nucleocapsid protein induced protective immunity in bank voles ...199910486924
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
analysis of puumala hantavirus genome in patients with nephropathia epidemica and rodent carriers from the sites of infection.reverse transcription-polymerase chain reaction (rt-pcr) followed by sequence and phylogenetic analyses were used to study specimens from nine finnish nephropathia epidemica (ne) patients admitted to hospital during the epidemic in winter 1996-1997. blood samples from six patients were found to be positive for the partial m- and/or s-segment sequences of puumala hantavirus (puuv). analyses of these sequences (nt 2168-2610 for the m segment, and nt 819-1082 for the s segment) revealed six distinc ...199910502274
phage-displayed peptides mimicking the discontinuous neutralization sites of puumala hantavirus envelope glycoproteins.we selected peptide ligands mimicking the surface structure of discontinuous binding sites of puumala hantavirus-neutralizing monoclonal antibodies from a random 18-amino acid peptide library containing a disulfide bridge in a fixed position and displayed on a filamentous phage. the varying of selection conditions, either by shortening of the association time or by competitive elution with antigen, was crucial for the selection of peptide inserts that could be aligned with the primary sequences ...199910502511
epidemiological study of nephropathia epidemica in finland 1989-96.this study presents data on 33,000 serum samples studied from july 1989 to june 1996 in finland, with 6,701 serologically confirmed puumala virus (puu) infections. in addition, a puu serosurvey of 8,000 sera from finland is presented. on average, 957 puu infections were detected annually, resulting in an incidence of 19/100,000; mortality was less than 0.1%. the infection was most common in the district of ita-savo with an incidence of 90/100,000. the seasonal peak was in november-december; howe ...199910576121
chronic renal failure after puumala virus infection.chronic renal failure has never been described after puumala hantavirus infection, which usually causes acute renal failure with spontaneous full recovery. we report a 15-year-old boy who presented with puumala hantavirus infection and initial severe acute renal failure. his renal function gradually improved, but more than 2 years after the acute episode it was still moderately impaired, with a creatinine clearance of about 60 ml/min per 1.73 m(2)199910603154
dynamics of puumala hantavirus infection in naturally infected bank voles (clethrinomys glareolus).specific features of hantavirus infection in bank vole (clethrionomys glareolus) were studied in the endemic area of hemorrhagic fever with renal syndrome (hfrs) in the foothills of the ural mountains, using long-term observations on living animals by the capture-mark-recapture (cmr) method. the results demonstrated that the infection naturally circulating in the voles is chronic (lasting for up to 15 months) and asymptomatic, with a peak of puumala virus accumulation and release from the organi ...199910664394
a neutralizing recombinant human antibody fab fragment against puumala hantavirus.a combinatorial human antibody fab pcomb3h library, generated from splenic lymphocytes of a puumala hantavirus (puuv) immune individual, was selected against puuv using the phage display technique. panning was carried out with antigens immobilized by mabs directed to the two puuv envelope glycoproteins g1 and g2. thirteen fabs, with reactivity directed to puuv and specifically the g2 protein, as assessed by immunofluorescence and elisa respectively, were isolated in crude preparations. by a focu ...200010686029
serologic evidence of puumala virus infection in wild moose in northern sweden.puumala (puu) virus is the causative agent of nephropathia epidemica, the scandinavian form of hemorrhagic fever with renal syndrome. the infection is acquired by airborne transmission of puu virus from its rodent reservoir, the bank vole. besides serologic data indicating that the virus may spread also to heterologous rodents, there is little information on the susceptibility of wild living animals to puu virus. we studied the occurrence of antibodies to puu virus in serum samples from 427 wild ...200010761733
[clinical case of the month. a new case of nephropathia epidemica due to puumala virus].nephropathia epidemica due to puumala virus has already been described in belgium. its evolution is usually favourable. the main symptoms are fever, a decrease platelet count, proteinuria and acute renal insufficiency, which, in an epidemiological context, quickly point the correct diagnosis. acute and transitory myopia is typical. nevertheless, the clinical presentation, including multisystemic symptoms may lead to the false diagnosis of an acute bacterial or immune disease.200010769579
spatial and temporal dynamics of puumala hantavirus infection in red bank vole (clethrionomys glareolus) populations in belgium.dynamics of hantavirus infection and population densities in rodents were investigated from 1996 to 1999 in southern belgium. evidence of puumala infection was restricted to clethrionomys glareolus. although the serotype was not determined, antibodies against hantavirus were also found in eight apodemus sylvaticus. in fall 1996, the seroprevalence in c. glareolus was high (20.1%, 37 of 184) and the infection was widely distributed in the area studied whereas a focal occurrence of positive rodent ...200010773322
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
immunoglobulin a responses to puumala hantavirus.puumala hantavirus (puuv) causes nephropathia epidemica (ne), a form of haemorrhagic fever with renal syndrome that occurs in northern and central europe. the immunoglobulin a (iga) response in ne patients was studied. the levels of total serum iga in acute-phase samples from ne patients were found to be significantly elevated when compared with the levels in healthy controls. elisas for detection of the iga1 and iga2 responses against each puuv structural protein (n, g1 and g2) were developed a ...200010811929
a case-control study after a hantavirus infection outbreak in the south of belgium: who is at risk?puumala is the most common hantavirus serotype in europe and is spread mainly by the red bank vole. between 1 july 1992 and 31 january 1994, an outbreak of puumala virus-induced nephropathia epidemica (ne) occurred in the belgian ardennes. serologically confirmed cases (n = 41) were compared with two groups of asymptomatic seronegative controls. risks identified included sighting of living rodents, exposure to rodent droppings, and trapping rodents during the 4 weeks preceding onset of symptoms. ...199910825047
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
clinical aspects of nephropathia epidemica (puumala virus infection) in europe: a review.nephropathia epidemica (ne) is a prevalent zoonosis throughout europe and is caused by the puumala type of hantavirus. the incidence of ne varies in a cyclic fashion, with peaks occurring every 3rd to 4th year, coinciding with peaks in vole populations. the clinical course of ne is generally milder than haemorrhagic fever with renal syndrome caused by hantaviruses in other parts of the world. typically, ne has a sudden onset with fever, headache, backpain and gastrointestinal symptoms. however, ...200010826895
diagnostic potential of puumala virus nucleocapsid protein expressed in drosophila melanogaster cells.puumala virus (puu) nucleocapsid protein (n) was expressed in insect cells by using the drosophila expression system (des; invitrogen bv, groningen, the netherlands). stable transfectants were established by hygromycin b selection and showed continuous expression of the recombinant protein (des-puu-n) for at least 5 months. the antigenic property of des-puu-n was shown to be identical to that of native puu n when examined with a panel of hantavirus-specific monoclonal antibodies. enzyme-linked i ...200010834996
complement activation in nephropathia epidemica caused by puumala hantavirus.nephropathia epidemica (ne) is a hemorrhagic fever with renal syndrome caused by puumala hantavirus. there is considerable variability in the clinical severity of ne. its pathogenesis is largely unknown and data on complement activation in ne are scant. we sought here to establish how the complement system behaves during ne and whether the variation in the clinical outcome is related to the activation of complement.200010879661
[baculovirus: an example of an insect virus of use to humans].baculovirus is a viral pathogen of insects in general and lepidoptera in particular. the genome of this large virus consists of a circular, infectious bicatenary dna molecule. at the end of its replication cycle in insects, baculovirus produces a large quantity of at least two proteins, i.e., polyedrine and polypeptide p10. these proteins are essential for transmission of the virus in nature, but are not necessary in cell cultures. using molecular recombinant techniques, one or both of the genes ...199910901857
[outbreak of hemorrhagic fever with kidney syndrome in egor'ev district of moscow region].epizootological, serological, and molecular virological analysis of an outbreak of hemorrhagic fever with renal syndrome (hfrs) in the egoryevsk district of moscow region (september 1995-january 1996) has been carried out. hantavirus (puumala) antigen and virus-specific antibodies were isolated from bank voles captured in the endemic focus. anti-puumala antibodies were detected in the sera of all hfrs patients and in 2% healthy residents of the endemic focus. analysis of nucleotide sequence (rna ...200010971964
[the spread of hantaviruses in western siberia].studies made in west siberia established the existence of at least 4 hantavirus types: puumala, tula, topografov, and dobrava/belgrade. the authors detected puumala virus genovariants in voles, tula virus in sagebrush and narrow-skulled voles, and topografov virus in siberian lemmings. the etiological role of the hantavirus dobrada/belgrade was defined in the structure of morbidity of hemorrhagic fever with the renal syndrome. in russia, hantaviruses were first detected in mites: a hantavirus an ...200010981407
evaluation of two commercially available immunoassays for the detection of hantavirus antibodies in serum samples.hantaviruses are members of the family bunyaviridae and the spectrum of clinical symptoms in humans may vary from sub-clinical to severe haemorrhagic fever with renal syndrome (hfrs) or pulmonary syndrome (hps). several serotypes have been described from which at least five are pathogenic to humans. each serotype has a different animal reservoir and geographical distribution. in the acute phase of the disease the clinical diagnosis may be confirmed by serology or by polymerase-chain reaction (pc ...200010996116
renal function and blood pressure five years after puumala virus-induced nephropathy.nephropathia epidemica (ne) is a mild form of hemorrhagic fever with renal syndrome caused by puumala hantavirus. its long-term prognosis is considered favorable. some reports suggest, however, that a previous hantavirus infection increases the risk of hypertension.200011012905
dna vaccination of mice with a plasmid encoding puumala hantavirus nucleocapsid protein mimics the b-cell response induced by virus infection.inoculation of naked dna has been applied for the development of prophylactic and therapeutic vaccines against different viral infections. to study the humoral immune response induced by dna vaccination we cloned the entire nucleocapsid protein-encoding sequence of the puumala hantavirus strain vranica/hällnäs into the cmv promoter-driven expression unit of the plasmid pcdna3, generating pcdna3-vr1. a single dose injection of 50 microg of plasmid dna into each m. tibialis anterior of balb/c mice ...200111035190
puumala (puu) hantavirus strain differences and insertion positions in the hepatitis b virus core antigen influence b-cell immunogenicity and protective potential of core-derived particles.hepatitis b virus (hbv) core-derived chimeric particles carrying a puumala (puu) hantavirus (strain vranica/hällnäs) nucleocapsid (n) protein sequence (aa 1-45), alternatively inserted at three distinct positions (n-, c-terminus, or the internal region), and mosaic particles consisting of hbv core as well as core/puu (vranica/hällnäs) n (aa 1-45) readthrough protein were generated. chimeric particles carrying the insert at the n-terminus or the internal region of core induced some protective imm ...200011040127
first case of puumala virus infection in greece. 200011073146
evidence of puumala hantavirus infection in red foxes (vulpes vulpes) in belgium. 200011083049
molecular evolution of puumala hantavirus in fennoscandia: phylogenetic analysis of strains from two recolonization routes, karelia and other members of the genus hantavirus: in the family bunyaviridae:, puumala virus (puuv) is thought to be co-evolving with its natural host, the bank vole clethrionomys glareolus. to gain insight into the evolutionary history of puuv in northern europe during the last post-glacial period, we have studied wild-type puuv strains originating from areas along two postulated immigration routes of bank voles to fennoscandia. full-length sequences of the s rna segment and partial sequences (nt 216 ...200011086113
expression of a human, neutralizing monoclonal antibody specific to puumala virus g2-protein in stably-transformed insect cells.we cloned the heavy- and light-chain antibody genes of a human x (humanxmouse) trioma secreting a neutralizing, igg monoclonal antibody to the g2-protein of puumala virus. the antibody genes were inserted separately into plasmid transfer vector piei-4 such that the genes were under control of the baculovirus immediate early gene promoter, iei. trichoplusia ni (tn) cells were co-transfected with these constructs and a selection plasmid containing a neomycin-resistance gene. cloned transformants e ...200011121551
t-helper and humoral responses to puumala hantavirus nucleocapsid protein: identification of t-helper epitopes in a mouse model.puumala hantavirus (puuv) is a rodent-borne agent causing nephropathia epidemica in humans, a milder form of haemorrhagic fever with renal syndrome occurring in fennoscandia, central europe and western russia. in this study we characterized the immunogenicity of an e. coli-expressed nucleocapsid (n) protein of puuv (strain kazan-e6) in inbred mice (balb/c, cba and c57/bl6). the recombinant n (rn) protein raised puuv-specific antibodies in all three tested murine haplotypes, and all igg subclasse ...200111125166
expression of immunogenic puumala virus nucleocapsid protein in transgenic tobacco and potato plants.transgenic plants, expressing recombinant proteins, are suitable alternatives for the production of relevant immunogens. in the present study, the expression of puumala virus nucleocapsid protein in tobacco and potato plants (nicotiana tabacum and solanum tuberosum) and its immunogenicity was investigated. after infection of leaf discs of sr1 tobacco and tuber discs of potato cv. "desiree" with the agrobacterium strain lba4404 (pal4404, pbinar-puu-s) containing the 1302 bp cdna sequence of s-rna ...200111210942
genetic characterization of puumala hantavirus strains from belgium: evidence for a distinct phylogenetic lineage.puumala hantavirus (puuv) sequences were recovered from red bank voles (clethrionomys glareolus) trapped between 1996 and 1998 in four localities of southern belgium: thuin, montbliart, momignies and couvin. in addition, three puuv isolates originating from bank voles trapped in the 1980s in southern (montbliart) and northern (turnhout) belgium were genetically characterized. analysis of the complete s and partial m segment sequences showed that the belgian puuv strains constitute a genetic line ...200111226569
[respiratory manifestations of hemorrhagic fever with renal syndrome. retrospective study of 129 cases in champagne-ardenne and lorraine].the contradiction between airborne transmission of puumala virus and the low rate of airway manifestations reported in hemorrhagic fever with renal syndrome (hfrs) caused by this virus led us to conduct this study to check whether the incidence of respiratory manifestations may have been underestimated.200111244810
evaluation of a pan-reactive hantavirus enzyme immunoassay and of a hantavirus immunoblot for the diagnosis of nephropathia epidemica.nephropathia epidemica (ne) caused by the hantavirus serotype puumala (puuv) is endemic in large parts of europe. the prognosis of this disease is usually good. however, a rapid serological diagnosis is important to differentiate ne from potentially more severe renal conditions.200111255099
new immunochromatographic rapid test for diagnosis of acute puumala virus infection.a new immunochromatographic rapid test, poc puumala (erilab ltd., kuopio, finland), for detection of acute-phase puumala virus (puuv) infection was developed based on a highly purified baculovirus-expressed puuv nucleocapsid protein antigen and lateral immunodiffusion techniques. after addition of sample (5 microl of serum, plasma, or fingertip blood) and buffer, puuv-specific immunoglobulin m (igm) antibodies, if present, together with the gold-conjugated anti-human igm, formed a specific color ...200111376049
[viral infectious and chromosome aberrations in bank vole from natural and laboratory populations].the frequency of chromosome damage was studied in the carriers of virus of the hemorrhagic fever with renal syndrome (puumala virus) and in noninfected animals from two laboratory colonies and two natural populations of bank vole. in the laboratory colony, where puumala virus persisted for three years, multiaberrant ("rogue") cells were found in the bone marrow; the mean frequencies of both structural and numeral chromosome abnormalities were significantly enhanced. in the other laboratory colon ...200111421123
modifying the cellular transport of dna-based vaccines alters the immune response to hantavirus nucleocapsid protein.puumala virus is a member of the hantavirus genus (family bunyaviridae) and is one of the causative agents of hemorrhagic fever with renal syndrome (hfrs) in europe. a genetic vaccination approach was conducted to investigate if the immune response could be modulated using different cellular secretion and/or localisation signals, and the immune responses were analysed in balb/c mice and in a bank vole infectious model. rodents vaccinated with dna constructs encoding the antigen fused to an amino ...200111427253
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
polymorphism of the cytokine genes in hospitalized patients with puumala hantavirus infection.nephropathia epidemica (ne) is a mild type of haemorrhagic fever with renal syndrome caused by puumala (puu) hantavirus. the clinical course of ne varies from asymptomatic to fatal. the aim of this study was to establish whether polymorphisms in the cytokine genes are associated with susceptibility to and outcome of ne.200111427627
highly sensitive taqman pcr detection of puumala increasing number of clinical cases of hantavirus infections have been reported from various regions in asia, europe and north america. hantaviruses (family bunyaviridae, genus hantavirus) are enveloped and possess a single-stranded trisegmented rna genome of negative polarity. rodents or insectivores are natural hosts of hantaviruses and transmit the virus to humans chiefly by aerosolisation. these viruses are the causative agents of haemorrhagic fever with renal and pulmonary syndromes. in ...200111489422
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
infections of the central nervous system of suspected viral origin: a collaborative study from finland.we studied 3231 patients with acute central nervous system (cns) symptoms of suspected viral origin to elucidate the current etiologic spectrum. in 46% of the cases, a viral finding was observed. varicella-zoster virus (vzv) was the main agent associated with encephalitis, as well as meningitis and myelitis. vzv comprised 29% of all confirmed or probable etiologic agents. herpes simplex virus (hsv) and enteroviruses accounted 11% each, and influenza a virus 7%. vzv seems to have achieved a major ...200111582512
comparison of a new immunochromatographic rapid test with a commercial eia for the detection of puumala virus specific igm antibodies.hantaviruses are associated with two human diseases: haemorrhagic fever with renal syndrome (hfrs) and hantavirus pulmonary syndrome (hps). puumala virus (puuv), which is one of the hantaviruses, is a causative agent of nephropathia epidemica (ne), a mild form of hfrs.200111595586
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
molecular evolution of puumala hantavirus.puumala virus (puuv) is a negative-stranded rna virus in the genus hantavirus, family bunyaviridae. in this study, detailed phylogenetic analysis was performed on 42 complete s segment sequences of puuv originated from several european countries, russia, and japan, the largest set available thus far for hantaviruses. the results show that puuv sequences form seven distinct and well-supported genetic lineages; within these lineages, geographical clustering of genetic variants is observed. the ove ...200111689661
[hantavirus infection epidemiology in belgium].in europe, puumala (puu) is a hantavirus responsible for a human disease called nephropathia epidemica and its natural reservoir is the red bank vole, (clethrionomys glareolus). although the population densities and the prevalence rates of infection were high in red bank voles in southern belgium during the 1996 and 1999 epidemic years, the percentages of infected rodents were low in 1997 and 1998, when only a few positive sites were found. antibodies against puu virus were mainly detected in th ...200111697188
[hemorrhagic fever with renal syndrome].puumala hantavirus is the most common hantavirus infection in western europe. the causative agent, puumala virus, is a member of the hantavirus genus in the bunyaviridae family. the natural hosts of hantaviruses are chronically, but asymptomatic infected rodents, which transmit the virus to human in their excretions. puumala virus is carried by the bank vole, clethrionomys glareolus. hemorrhagic fever with renal syndrome (hfrs) caused by puumala virus in france or belgium is very similar to the ...200111715607
mesangiocapillary glomerulonephritis caused by puumala hantavirus infection.nephropathia epidemica induced by puumala hantavirus typically causes acute reversible renal function impairment. a typical renal biopsy finding is acute tubulointerstitial nephritis with slight glomerular mesangial changes. we describe here 5 patients who developed the nephrotic syndrome during the convalescent phase of an otherwise typical acute febrile nephropathia epidemica. renal biopsy of all patients disclosed type i mesangiocapillary glomerulonephritis (mcgn). a clinical remission of the ...200111721157
first molecular evidence for puumala hantavirus in slovakia.we report on the first puumala hantavirus nucleotide sequence (strain opina-916) amplified from a bank vole trapped in slovakia, central europe. phylogenetic analysis of the s-segment sequence grouped the virus within the western/central european sublineage of puumala virus. in the neighborhood of the rodent trapping site two cases of human infection by the puumala virus were verified.200111724269
wild-type puumala hantavirus infection induces cytokines, c-reactive protein, creatinine, and nitric oxide in cynomolgus macaques.hantaviruses cause two severe human diseases: hemorrhagic fever with renal syndrome (hfrs) and hantavirus pulmonary syndrome (hps). approximately 200,000 cases are reported annually, and there is to date no specific treatment available. a major obstacle in studying the medical aspects of hfrs and hps has been the lack of an adequate animal model. here we show that infection of cynomolgus macaques by wild-type puumala hantavirus resulted in typical signs of hfrs including lethargy, anorexia, prot ...200211739712
[oh, christmas tree!]. 199811757152
increased glomerular permeability in patients with nephropathia epidemica caused by puumala hantavirus.nephropathia epidemica (ne) is the scandinavian type of haemorrhagic fever with renal syndrome. usually heavy transient proteinuria is present at the onset of the disease.200211812874
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
[puumala virus infection (nephropathia epidemica) as different diagnosis of acute renal failure].puumala virus infection (nephropathia epidemica) as different diagnosis of acute renal failure.200211894176
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