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At least 19 recordsLinked to original sources

PubMed2002

Generation of recombinant vaccinia viruses expressing Puumala virus proteins and use in isolating cytotoxic T cells specific for Puumala virus.

Puumala (PUU) virus causes a form of hemorrhagic fever with renal syndrome (HFRS), called nephropathia epidemica (NE), in Europe. HFRS is characterized by an increased capillary permeability, which we hypothesize is caused by hyperactivation of the host immune system, especially cellular immune responses. To identify cytotoxic T lymphocytes (CTLs) specific for the PUU virus from NE patients, we have made recombinant vaccinia viruses expressing PUU virus proteins, the nucleocapsid (N) and two surface glycoproteins, G1 and G2. Recombinant vaccinia viruses carrying the N or the first half of the G2 cDNA under the control of a strong synthetic promoter were made. To express G1 and the second half of the G2 proteins, however, we needed to use a T7 expression system, where the T7 RNA polymerase is produced from another recombinant vaccinia virus co-infecting the same cells. These recombinant vaccinia viruses were used to detect and clone PUU virus-specific CTLs from the peripheral blood mononuclear cells of NE patients. An HLA-A24-restricted CTL line recognizing the G2 protein was isolated and its 9-mer epitope was determined.

Animals↗

PubMed1995

A vaccinia virus-vectored Hantaan virus vaccine protects hamsters from challenge with Hantaan and Seoul viruses but not Puumala virus.

To investigate the ability of a vaccinia virus-vectored vaccine expressing the M and the S segments of Hantaan (HTN) virus (C. S. Schmaljohn, S. E. Hasty, and J. M. Dalrymple, Vaccine 10:10-13, 1992) to elicit a protective immune response against other hantaviruses, we vaccinated hamsters with the recombinant vaccine and challenged them with HTN, Seoul (SEO), or Puumala (PUU) virus. Neutralizing antibodies to HTN virus were found in all vaccinated hamsters both before and after challenge. Neutralizing antibody titers to SEO virus were present at low levels or were undetectable after two immunizations with the vaccine but were positive in all vaccinated hamsters after challenge with SEO virus and were also positive in control animals that were not challenged. Neutralizing antibodies to PUU virus were observed only in hamsters previously challenged with PUU virus. To assay for virus in the blood and tissues of the hamsters, we developed a nested reverse transcriptase (RT)-PCR with cross-reactive outer primers and serotype-specific inner primers. The RT-PCR specifically detected as little as 1 PFU of virus in serum containing high-titer neutralizing antibodies and was more sensitive than immunofluorescent antibody staining for detecting virus in lung and kidney specimens of infected hamsters. By using the RT-PCR, we found that vaccinated hamsters, challenged with HTN or SEO virus, neither were viremic nor had evidence of virus in their lungs or kidneys. In contrast, vaccinated hamsters challenged with PUU virus were viremic and had PUU virus-specific nucleic acid in their organs.

Animals↗

PubMed2006

Regions of importance for interaction of puumala virus nucleocapsid subunits.

Puumala virus (PUUV) is a hantavirus that causes a mild form of hemorrhagic fever with renal syndrome in northern and central Europe, and in large parts of Russia. The nucleocapsid (N) protein encoded by hantaviruses plays an important role in the life-cycle of these viruses, and one important function for the N-protein is to oligomerize, surround and protect the viral RNAs. We have identified amino- and carboxy-terminal regions involved in PUUV N-N interactions, which comprise amino acids 100-120 and 330-405. Our findings strengthen the hypothesis that the amino-terminus of the N-protein of hantaviruses holds a more regulatory function regarding N-N interactions, while conserved residues in the carboxy-terminal region, F335 together with F336 and W392, in concert with Y388 and/or F400 seems to play a more critical role in the PUUV N-N formation. This study provides evidence that the amino-terminal regions involved in the N-N interaction of Puumala virus are similar to those reported for Seoul virus (SEOV) and to some extent Hantaan virus (HTNV), even though the identity between PUUV N and SEOV/HTNV N is markedly lower than between PUUV N and Tula virus (TULV) N or Sin Nombre virus (SNV) N.

Hemorrhagic Fever with Renal Syndrome↗

PubMed1998

Prevalence of antibodies specific to Puumala virus among farmers in Sweden.

OBJECTIVES: 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 Puumala virus occurs endemically only in the northern and central parts of Sweden was also tested. METHODS: Serum samples from 910 farmers and 663 referents living in various rural parts of Sweden were tested with an enzyme-linked immunosorbent assay, using a recombinant nucleocapsid protein of Puumala virus as the antigen. RESULTS: North of a latitude of 59 degrees N, the prevalence of Puumala virus antibodies was significantly higher among farmers (12.9%) than among referents (6.8%). In the southern areas, antibodies to Puumala virus were rare, and altogether only 2 of 459 persons had antibodies. Seropositive persons did not differ from seronegative ones with regard to blood pressure, and they did not comprise cases of chronic renal disease. CONCLUSIONS: Serological evidence confirmed that the exposure of humans to Puumala virus is firmly restricted to the northern and central parts of Sweden. In addition the evidence indicated that, in this region, farming is associated with an increased risk of contracting hantavirus infection.

Adult↗

PubMed2003

Patterns of Puumala virus infection in Finland.

Puumala hantavirus infection is prevalent throughout most of Europe, and in endemic areas it may be the most common cause of acute renal failure. To evaluate trends in incidence of Puumala virus infections in Finland, we analysed national surveillance data in 12-month periods from March 1995 to February 2002. During this time, 8184 laboratory-confirmed cases were notified to the National Infectious Disease Register. Three epidemic periods were identified, for which the number of cases was more than 1400 (there were approximately 600-900 cases per non-epidemic period). The incidence of Puumala hantavirus infection varied by geographic region during the study period, and the overall number of cases may be increasing.

Adolescent↗

PubMed2003

Expression of the nucleoprotein of the Puumala virus from the recombinant Semliki Forest virus replicon: characterization and use as a potential diagnostic tool.

Puumala virus (Bunyaviridae family, Hantavirus genus) causes a mild form of hemorrhagic fever with renal syndrome (HFRS) called nephropathia epidemica in northern and central Europe. Serological tests are used for diagnosis, but antigen production is difficult because the virus grows poorly in tissue culture. We expressed the N protein (nucleoprotein) of Puumala virus via the Semliki Forest virus (SFV) replicon in mammalian cells and compared its antigenic properties with those of the native antigen derived from Puumala virus-infected cells. Detection of immunoglobulin G or immunoglobulin M by enzyme-linked immunosorbent assay (ELISA), micro -capture ELISA, and indirect immunofluorescence assay was (at least) as effective with the recombinant antigen as with the native antigen when HFRS patient sera or organ washes from wild rodents were tested. No nonspecific reaction was observed. Thus, the SFV-expressed N protein of Puumala virus appears as a valid antigen, specific and sensitive for serological investigations.

Animals↗

PubMed1998

Hemorrhagic fever (Puumala virus infection) with ocular involvement.

BACKGROUND: 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. PATIENT AND METHODS: Comprehensive and repeated ophthalmic examinations of a previously healthy 35-year-old woman with acute Puumala virus infection were performed. Special attention was paid to ophthalmic A-scan ultrasound measurements and simultaneous blood chemistry tests. RESULTS: The ocular manifestations of this patient's illness included transient myopia, low intraocular pressure, conjunctival hemorrhages and changes of intraocular dimensions. There was forward movement of the anterior diaphragm and thickening of the crystalline lens, which occurred simultaneously with prominent fluctuations in the electrolyte balance, especially potassium. CONCLUSIONS: The observed changes in intraocular dimensions may have been caused by simultaneous fluctuations in electrolyte and osmotic balance, which could explain the myopic shift. The symmetry of the ocular measurements implied a systemic infection as the underlying reason for the ophthalmic symptoms and signs.

Adult↗

PubMed1995

Nucleotide and deduced amino acid sequences of the M and S genome segments of a Swedish Puumala virus isolate.

The Swedish Puumala (PUU) virus strain Vindeln 83-L20, isolated from a bank vole trapped in 1983 near Vindeln, Västerbotten county, Sweden, was characterized by nucleotide sequence analysis. The coding region of the M segment was determined by PCR followed by direct sequencing and the entire S segment was characterized by cloning and nucleotide sequence analysis. The genomic organization was found to be very similar to that of other PUU virus strains regarding open reading frames, polypeptide sizes and potential glycosylation sites. According to phylogenetic analysis 83-L20 was found to represent a new lineage within the Puumala virus serotype in the Hantavirus genus. The M segment sequence of 83-L20 was found to be more closely related to the Finnish PUU virus strains than to strains from Central Europe or from Russia. The evolutionary origin of the S segment was not as clearly resolved since the branching points of all PUU virus strains in the phylogenetic tree were nearly the same.

Amino Acid Sequence↗

PubMed1997

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 Austria, five species of rodents were trapped and screened for virus antibodies, antigen, and RNA. Hantaviruses were detected in two species, Cl. glareolus and M. arvalis, by reverse transcription-polymerase chain reaction (RT-PCR). RT-PCR products from Cl. glareolus tissues yielded a unique Puumala virus sequence distinct from Puumala virus sequences reported from other parts of Europe. RT-PCR products from M. arvalis tissues yielded two genetically distinct Tula virus sequences, one similar to sequences reported from Slovakia and the Czech Republic and another that appears to be a novel genetic variant of Tula virus. This is the first confirmed report of hantaviruses in Austria.

Animals↗

PubMed1993

Puumala virus antibody and immunoglobulin G avidity assays based on a recombinant nucleocapsid antigen.

Puumala virus is the causative agent of nephropathia epidemica (NE), a hantavirus infection which occurs widely in northern and central Europe and is generally diagnosed by the indirect immunofluorescence (IF) method. We have now expressed the Puumala virus Sotkamo strain nucleocapsid (N) protein-coding S genome segment as a beta-galactosidase fusion protein in Escherichia coli by using the pEX2 expression vector. The recombinant protein was purified by cutting the protein band from an agarose gel, melting the agarose, and removing the protein by freezing, incubation on ice, and centrifugation. The recovery was about 1 to 5 mg/200 ml of bacterial suspension, sufficient for coating 100 to 500 enzyme immunoassay microtiter plates. In a study of 312 IF-positive and 233 IF-negative serum samples from NE patients, the recombinant-N-protein enzyme immunoassay detected immunoglobulin G antibodies to Puumala virus with 97.8% sensitivity and 98.5% specificity compared with the IF test results. In addition, an immunoglobulin G avidity enzyme immunoassay was developed and used successfully to diagnose acute NE from a single serum sample. The results demonstrate that the bioengineered antigen is suitable for use in routine diagnostic assays for Puumala virus immunity and recent infection.

Adolescent↗

PubMed2001

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 segment of a Puumala virus, transgenic tobacco and potato plants expressed the Puumala virus nucleocapsid protein under control of the cauliflower 35S promoter. The recombinant proteins were found to be identical to the authentic Puumala virus nucleocapsid protein as analyzed by immunoblotting. Expression of the nucleocapsid protein was investigated over four plant generations (P to F4) and found to be stable (1 ng/3 microg dried leaf tissue). Transgenic tobacco plants were smaller compared to controls. The transformed potato plants were morphologically similar to control plants and produced tubers as the control potatoes. The S-antigen was expressed at a level of 1 ng protein/5 microg and 1 ng protein/4 microg dried leaf and root tissues, respectively, and remained stable in the first generation of vegetatively propagated potato plants. The immunogenicity of the Puumala virus nucleocapsid protein expressed in Nicotiana tabacum and Solanum tuberosum was investigated in New Zealand white rabbits. They were immunized with leaf extracts from transgenic tobacco and potato plants, and the serum recognized Puumala virus nucleocapsid protein. Transgenic plants expressing hantaviral proteins can thus be used for the development of cost-effective diagnostic systems and for alternative vaccination strategies.

Animals↗

PubMed1997

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 were under control of the baculovirus polyhedrin or p10 promoters, respectively. The transfer vector plasmid was cotransfected into cultured Spodoptera frugiperda (Sf9) cells with linearized DNA of the baculovirus Autographa californica nuclear polyhedrosis virus, and recombinant baculoviruses were selected by plaque formation on monolayers of Sf9 cells. Expression and secretion of an IgG monoclonal antibody was confirmed by assay of recombinant-infected Sf9 cell supernatants for the presence of the heavy and light chains. Specificity of the expressed human antibody was determined by immune-precipitation of radiolabeled Puumala virus proteins and by ELISA with Puumala virus-infected cell lysates. Similar quantities of the expressed IgG and the authentic monoclonal antibody neutralized Puumala virus in plaque-reduction neutralization assays. Neither the authentic nor the recombinant antibody could passively protect hamsters from challenge with Puumala virus; however, our results demonstrate the potential of this methodology for production of biologically active neutralizing antibodies.

Amino Acid Sequence↗

PubMed2000

[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.

Acute Kidney Injury↗

PubMed1999

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 earlier and more often than did the comparison group. In the province of Mikkeli with the highest incidence (70/100,000), the risk ratio was 5.1 (95% confidence interval (CI) 3.0-8.4) for 20- to 29-year-old farmers; in the older age groups, the risk was still increased but the risk ratios were lower. The peak incidence in the comparison group was 10 years later (age group 30-39 years). For the whole country, the result was similar although less marked. The average risk ratio adjusted by age, sex, and geographic variation was 1.7 (95% CI 1.5-1.8) for the whole country and 1.9 (95% CI 1.5-2.3) for the Mikkeli province, where 80% of Puumala virus infections among young farmers could be estimated to be attributable to occupation.

Adult↗

PubMed2002

[Puumala virus infection (nephropathia epidemica) as different diagnosis of acute renal failure].

UNLABELLED: Puumala virus infection (nephropathia epidemica) as different diagnosis of acute renal failure. HISTORY: A 34-year old patient presented in reduced status with a sudden onset of fever, headache, backpain, abdominal pain, mild diarrhea, nausea with vomiting, and blurred vision. Within a few days an acute renal failure developed. INVESTIGATIONS: On admittance there was thrombocytopenia of 27/nl, CRP of 109 mg/l and proteinuria of 5 g/l, moderate glucosuria and erythrocyturia of 250/microliter. Renal biopsy showed acute hemorrhagic interstitial nephritis. DIAGNOSIS, THERAPY AND FOLLOW UP: Diagnosis of nephropathia epidemica was proven by puumala-virus IgM- and later IgG-antibodies. Hantaan-antibodies were negative. Maximum serum creatinine of 640 micromol/l and urea of 30.5 mmol/l developed on the 5(th) day after admission. Without specific therapy the patient recovered fast and there were no persisting abnormalities during a 2-year follow up. CONCLUSION: In young patients with acute renal failure of unknown origin with the above symptoms hantavirus-infection with the subtypes puumala and dobrava should be considered in Central Europe.

Acute Kidney Injury↗

PubMed1993

Nucleotide and deduced amino acid sequences of the M and S genome segments of two Puumala virus isolates from Russia.

Hemorrhagic fever with renal syndrome (HFRS) is caused by viruses in the Hantavirus genus, family Bunyaviridae. Three serologically distinct hantaviruses, Hantaan, Seoul and Puumala viruses, are known to cause HFRS. We report here, for the first time, gene sequences of two human Puumala virus isolates, P360 and K27, obtained in an HFRS endemic region of the former Soviet Union. We compared the nucleotide sequences and the derived amino acid sequences of their gene products to a Puumala virus isolate from rodents.

Amino Acid Sequence↗

PubMedDate not supplied

Haemorrhagic fever with renal syndrome: evaluation of ELISA for detection of Puumala-virus-specific IgG and IgM.

IgM and IgG ELISA to Puumala virus were evaluated using sera from patients with haemorrhagic fever with renal syndrome (HFRS) from different geographical regions: Sweden, Denmark, Norway, Belgium and the European USSR. IgM ELISA proved useful in the diagnosis of HFRS in patients from all the regions mentioned above. Specific IgM could be detected as early as day 1 post onset of disease, and patients remained IgM-positive for several months. Specific IgG ELISA antibodies were also frequently detected in acute sera, and acute-convalescent serum pairs often failed to show a significant titre rise or increase in optical density (OD) values. This limits the use of IgG ELISA in patient diagnosis. Sera collected 2 years after infection revealed higher IgG ELISA OD readings than convalescent sera, and very high values were still detectable 10 to 20 years postinfection. IgG ELISA is therefore useful for the testing of immunity and in seroepidemiological studies. Acute and convalescent sera from HFRS patients in Korea and the Asian USSR showed no or only very weak reactivity in the Puumala virus IgG and IgM ELISA. These results are consistent with the "one-way" crossing described earlier.

Adolescent↗

PubMed1993

Susceptibility of human cells to Puumala virus infection.

Nephropathia epidemica involves several organs including kidney, lung, liver and brain. To investigate the susceptibility of putative target cells to the agent responsible, Puumala virus, we screened established human cell lines of lung (WI-38, A-427, CCD-11Lu), kidney (A-704), liver (Hep G2), pharynx (Detroit 562), submaxillary gland (A-253) and neural (SK-N-MC, SH-SY5Y) origin as well as primary human kidney glomerular cells, endothelial cells and peripheral blood monocytes/macrophages. Propagation of the Sotkamo strain of Puumala virus was also tested in the primary kidney, spleen and lung cells of bank voles (the natural host of the virus). All of the primary cells and most of the established cell lines expressed viral protein, synthesized viral RNA and secreted infectious virus, except the neural SK-N-MC and SH-SY5Y cells. None of the tested cell types except the primary bank vole kidney cells could propagate the virus as efficiently as the Vero E6 cells. The observed host cell range is wide and consistent with a multiorgan involvement of Puumala virus. No cytopathic effects were seen in any of the infected cell cultures.

Animals↗