Dobrava hantavirus in Estonia: does the virus exist throughout Europe?
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Animals↗
Biomedical subjects
A Vaheri
Publications and source records attributed to A Vaheri.
Seroprevalence and coprevalence of HIV and HBsAg in Nigerian children with/without protein energy malnutrition.
In order to assess the seroprevalence and coprevalence of hepatitis-B surface antigen (HBsAg), human immunodeficiency virus-1 and -2 (HIV-1 and -2) antibodies in Nigerian children with/without protein energy malnutrition (PEM), we studied plasma specimens of 206 children with PEM and 200 apparently healthy reference children aged between 1 and 3 years by enzyme-linked immunosorbent assays (ELISA). HIV-seropositive cases were confirmed by immunoblotting (IB). Of the children studied, eight (4%) of the healthy and four (1.9%) of the malnourished (P = 0.22, Fisher's exact test) were positive for HIV-1 antibodies, 40 (20%) of the healthy and 54 (26%) of the malnourished (P = 0.14) were positive for HBsAg, and five (2.5%) of the healthy and four (1.9%) of the malnourished (P = 0.70) were positive for both HIV-1/HBsAg. No case of HIV-2 antibodies was found. While the seroprevalence of HBsAg was higher in the malnourished subjects, the reverse was the case with HIV antibodies. However, all the four HIV-1-positive malnourished children and five of eight of the HIV-1-positive reference children were simultaneously positive for HBsAg. This is the first epidemiological report on the seroprevalence and coprevalence of HIV and HBsAg in apparently healthy and malnourished Nigerian children.
Child, Preschool↗
Epidemiology of encephalitis in children. A prospective multicentre study.
UNLABELLED: We found 175 cases with acute encephalitis in a population of 791,712 children aged 1 month-15 years during a 2-year surveillance period in 1993-1994. The overall incidence was 10.5/100,000 child-years with the highest figure in children < 1 year of age, 18.4/100,000 child-years. The microbial diagnosis was considered proven or suggested in 110 cases (63%); varicella zoster, respiratory and enteroviruses comprised 61% of these, and adeno, Epstein Barr-, herpes simplex and rota viruses comprised 5% each. A clearcut change seems to have occurred in the aetiology of encephalitis. Mumps, measles, and rubella virus associated encephalitides have been almost eliminated. Varicella zoster, respiratory, and enteroviruses have increased in frequency and occur in younger age groups. New causes were identified, especially Chlamydia pneumoniae and HHV-6. Our data should assist in making a specific diagnosis and defining appropriate antimicrobial therapy. CONCLUSIONS: The spectrum of encephalitis in children has changed due to vaccination programs. The incidence, however, appears to be about the same due to increasing frequency of other associated old and new microbes.
Acute Disease↗
Luminometric microplate hybridization for detection of varicella-zoster virus PCR product from cerebrospinal fluid.
We modified and optimized a new microplate hybridization assay to detect the varciella-zoster virus (VZV) PCR product, and studied cerebrospinal fluid (CSF) samples of 287 patients with meningitis, encephalitis or other neurological diseases or symptoms. Specific antibodies to VZV and reference antigens were determined by enzyme immunoassay from serum and CSF, they were then compared with clinical findings and with the results obtained by VZV-PCR using different detection methods for VZV-specific amplified DNA. VZV DNA was found in the CSF of 25 patients using the microplate hybridization assay and chemiluminescence detection for amplified DNA. All 25 CSF samples were also positive in Southern blotting. Among the patients, 10 had chickenpox, 4 had shingles, and 11 had no rash at all. The detection rate of VZV-specific DNA by microplate hybridization was 30% higher than that obtained by conventional agarose gel electrophoresis. In most patients the diagnosis was confirmed by demonstrating specific intrathecal antibody production to VZV but not to other viruses. These results indicate the presence of VZV in the central nervous system (CNS) in many patients with chickenpox or shingles, and even in patients without a rash. The microplate hybridization assay based on chemiluminescence detection improves considerably the detection rate of the VZV-PCR product compared to agarose gel electrophoresis and will add to the list of recognized VZV infections in the CNS. It is especially useful in cases where there is no cutaneous manifestation.
Chickenpox↗
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 appeared to be at least as conserved as the S segment. Phylogenetic analysis based on the S, M and L segment sequences proposes that the three viral genes have a similar evolutionary history with no evidence for genome segment reassortment. Precise sequencing of the L segment termini demonstrated that the Puumala strains differ from the conserved sequences of the other hantaviruses at two positions.
Amino Acid Sequence↗
The ezrin protein family: membrane-cytoskeleton interactions and disease associations.
Ezrin, radixin, moesin and merlin form a subfamily of conserved proteins in the band 4.1 superfamily. Ezrin protein subfamily members act as linkers between the plasma membrane and the cytoskeleton. Members of the subfamily have been shown to interact with each other, with cell adhesion molecules such as CD44 and with F-actin. Recent data indicate that intercellular adhesion molecules 1 and 2 also interact with ezrin. The proteins are also involved in the redistribution of intercellular adhesion molecules and the organization of cell membrane structures. Merlin is a tumor suppressor that is involved in tumorigenesis of schwannomas and meningiomas. Merlin has the same overall protein structure as the other proteins in the subfamily but may have partially distinct functions.
Animals↗
Assessment of plasma fibronectin in malnourished Nigerian children.
BACKGROUND: Severe malnutrition is associated with septic infections. The concentrations of fibronectin, albumin, and transferrin in plasma were measured in three groups of children with protein-energy malnutrition, aged 1-3 years, each group comprising 20 children. The aim of which was to test whether plasma fibronectin, being an opsonic protein, was reduced in such children, and if it was a useful index for assessing the severity of malnutrition. METHODS: The concentrations of fibronectin, albumin, and transferrin in plasma were studied by enzyme immunoassay/ immunoblotting, spectrophotometry and immunoturbidimetry respectively. RESULTS: All values were significantly lower in the patients with malnutrition than in the age- and sex-matched well-nourished Nigerian reference children. Within the malnourished group, the fibronectin value was evenly reduced in all subgroups. Albumin and transferrin values were lowest in the patients with kwashiorkor, highest in the marasmic patients, and intermediate in the patients with marasmic kwashiorkor; the values correlated mutually in individual cases as well, but not with the fibronectin levels. Neither plasma fibronectin fragmentation nor tissue fibronectin was detected in any patient with malnutrition or in the reference subjects. CONCLUSIONS: The reduced plasma fibronectin values in these patients may be due to reduced synthesis by the liver, as evidenced by the equally reduced albumin and transferrin concentrations and/or to the multiple infections characteristic of the patients.
Biomarkers↗
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, Escherichia coli-expressed, or baculovirus-expressed nucleocapsid protein (N). Neutralization and immunofluorescence assays were included for comparison. Equally high sensitivities and specificities were obtained with three mu-capture-based IgM ELISAs using native, baculovirus-expressed, and E. coli-expressed N antigens, respectively, and by an ELISA based on purified E. coli-expressed full-length N adsorbed to solid phase. The assays based on truncated amino-terminal N proteins, including a commercially available PUU virus IgM ELISA, all showed lower sensitivities. For detection of PUU virus-specific IgG, ELISAs based on monoclonal antibody-captured native or baculovirus-expressed N antigens showed optimal sensitivities and specificities, while the assays based on E. coli-expressed N did not detect all PUU virus IgG-positive serum samples. A commercially available PUU virus IgG ELISA based on E. coli-expressed amino-terminal N showed a significantly lower sensitivity than those of all other IgG assays.
Antibodies, Viral↗
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 analysis of the partial M-and/or S-segment sequences obtained from three severely ill NE patients revealed three PUU strains related to but distinct from previously reported strains from Finland. The M-segment sequence of PUU from bank voles trapped near the probable site of infection for one of the patients showed 98.2% identity to that of the PUU strain obtained from the patient, suggesting a link between wild-type PUU from the natural focus and the NE case. The S-segment sequences from the patient and the bank voles, however, showed substantially lower identity (95.8%). As this difference in diversity for M and S genes (1.8 and 4.2%) is atypical for PUU genetic drift, one possibility is that the strain acquired at the putative place of infection is a reassortant one.
Adult↗
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 respective viral genomes revealed no differences in the coding region of the S gene. However, the noncoding regions of the S gene were found to be different at positions 26 and 1577. In one additional and independent adaptation experiment, all analyzed cDNA clones from the Vero E6-adapted variant were found to carry substitutions at position 1580 of the S segment, just 3 nucleotides downstream of the mutation observed in the first adaptation. No differences were found in the consensus sequences of the entire M segments from the wt and the Vero E6-adapted variants. The results indicated different impacts of the S and the M genomic segments for the adaptation process and selective advantages for the variants that carried altered noncoding sequences of the S segment. We conclude that the isolation in cell culture resulted in a phenotypically and genotypically altered hantavirus.
Adaptation, Physiological↗
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 functions. The peptide insert, CHWMFSPWC, when displayed on the phages, completely inhibited Puumala virus infection in cell culture at the same effective concentration as the eluting antibody specific for envelope glycoprotein G2. The binding of the phage clones to the virus and inhibition of infection were not necessarily coincident; Pro-6 was critical for virus inhibition, while consensus residues Trp-2 and Phe-4 were essential for binding. The strategy described can be applied to any virus for production of molecules mimicking the effect of neutralizing antibodies.
Animals↗
Chlamydia trachomatis detected in human placenta.
AIMS: To evaluate the relation between Chlamydia trachomatis infection and stillbirth, placental tissue was studied for the presence of C trachomatis. METHODS: Paraffin wax embedded placental tissue of a stillbirth fetus, born at the 36th week of gestation to a 21 year old mother with high serum antibody titres to C trachomatis immunotypes during pregnancy and who was culture positive to C trachomatis three years previously, was studied by in situ hybridisation, polymerase chain reaction, and immunohistochemistry for the presence of C trachomatis. RESULTS: C trachomatis was detected in placental specimens by in situ hybridisation and alkaline phosphatase antialkaline phosphatase staining in several sections, whereas control tissues were uniformly negative, indicating the presence of C trachomatis nucleic acid and antigen in the placenta. CONCLUSION: This is the first reported case in which C trachomatis has been demonstrated in the human placenta.
Adult↗
Cerebrospinal fluid plasminogen activator inhibitor-1 in patients with neurological disease.
AIM: To study cerebrospinal fluid (CSF) concentrations of plasminogen activator inhibitor type-1 (PAI-1) in patients with neurological disease. METHODS: CSF PAI-1 concentrations were measured in 51 patients with neurological disease and 20 reference subjects using an ELISA. The patient group comprised three patients with viral meningitis, 20 with encephalitis, nine with acute lymphoblastic (n = 7) and myeloid (n = 2) leukaemia (with central nervous system involvement), and 19 with multiple sclerosis. RESULTS: Raised PAI-1 concentrations were observed in patients with leukaemia, encephalitis and multiple sclerosis. There was no difference in the mean concentrations of PAI-1 in patients with meningitis when compared with the reference subjects. The highest mean (SEM) PAI-1 concentration was found in patients with leukaemia (1.28 (0.36) ng/ml), and the next highest in those with encephalitis (1.19 (0.20) ng/ml). these values were much higher than those in patients with viral meningitis. In a previous report, raised CSF tissue-type plasminogen activator (tPA) activities were detected in patients with multiple sclerosis, leukaemia and encephalitis, with mean activities in decreasing order. PAI-1 concentrations in the same patients were the reverse of their corresponding tPA activities, being higher in those with leukaemia and encephalitis, than in patients with multiple sclerosis. There was no association between CSF PAI-1 concentrations and age in either patients or controls. Similarly, there was no association between CSF PAI-1 concentrations and urokinase-type plasminogen activator (uPA). CONCLUSIONS: Raised CSF PAI-1 concentrations may be used as a non-specific marker of neurological disease. Moreover, PAI-1 may play an important role in regulating the functions tPA, and probably uPA, in CSF.
Adolescent↗
Neurofibromatosis 2 tumor suppressor protein colocalizes with ezrin and CD44 and associates with actin-containing cytoskeleton.
Neurofibromatosis 2 (NF2) protein (merlin; schwannomin) is a tumor suppressor involved in tumorigenesis of NF2-associated and sporadic schwannomas and meningiomas. The protein shares the domain structure of three homologous proteins: ezrin, radixin and moesin (ERM). ERM proteins function as membrane organizers and may act as linkers between plasma membrane molecules, such as CD44 and ICAM-2, and the cytoskeleton. We analyzed the distribution and effects of transfected NF2 protein in COS-1, CHO and 293 cells, and endogenous NF2 protein in U251 glioma cells. The distribution was compared to ezrin, CD44 and F-actin. Both transfected and endogenous NF2 protein localized underneath the plasma membrane in a pattern typical of an ERM protein. In COS-1 transfectants, NF2 protein typically codistributed with ezrin but, in cells with poorly developed actin cytoskeleton, it replaced ezrin in filopodia and ruffling edges. NF2 protein colocalized with CD44, which in transfected cells accumulated into restructured cell membrane protrusions. The association of CD44 and NF2 protein was further suggested by binding of CD44 from cellular lysates to recombinant NF2 protein. Interaction between NF2 protein and the actin-containing cytoskeleton was indicated by partial colocalization, by cytochalasin B-induced coclustering, and by retention of NF2 protein in the detergent-insoluble fraction. Transfected NF2 protein induced morphogenic changes. The cells contained restructured membrane extensions and blebs, and CHO cells expressing NF2 protein were more elongated than control transfectants. In conclusion, NF2 protein possesses functional properties of an ERM family member.
Actins↗
Myelitis associated with influenza A virus infection.
We report a patient presenting with myelitis after respiratory symptoms. A high level of antibodies to influenza A virus was measured in serum and cerebrospinal fluid (CSF), and the serum/CSF antibody ratio was 1.7, suggesting specific antibody production in the central nervous system. Magnetic resonance imaging of the spinal canal showed a contrast-enhanced swelling on the cervical medulla. Such a case would have warranted the use of antiviral therapy and calls to mind the neurotropic potential of influenza A viruses.
Antibodies, Viral↗
[Kaposi's sarcoma another new infectious disease?].
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AIDS-Related Opportunistic Infections↗
Inhibition of puumala and tula hantaviruses in Vero cells by MxA protein.
Human MxA protein is a type I Interferon-inducible intracytoplasmic protein, which mediates antiviral actions against a variety of negative-strand RNA viruses including influenza A, measles, and vesicular stomatitis viruses. Recently, it has also been shown that several members of the Bunyaviridae family are inhibited by MxA protein. The hantavirus genus in the Bunyaviridae family includes important human pathogenic viruses, e.g., Puumala (PUUV), Hantaan, and Sin Nombre viruses. Tula virus (TULV) is a new member of the genus, but its pathogenicity in man remains to be determined. As assumed by the similarities in replication strategy. MxA would be a good candidate molecule for antiviral action against these viruses, also. To gain more insight into the MxA action on PUUV, we studied PUUV and TULV replication in stably MxA genetransfected Vero cells. We show that MxA protein has the capacity to inhibit both viral protein and RNA accumulation in virus-infected cells. We also studied PUUV and TULV infection in MxA-transfected U-937 cell clones. In these cell lines both hantaviruses grew poorly, independent of whether the cells were expressing MxA or not Whether cell line-specific differences in the antiviral activity of MxA protein against hantaviruses exist cannot be conclusively determined due to the lack of productive infection of PUUV and TULV in U-937 cells.
Animals↗
ICAM-2 redistributed by ezrin as a target for killer cells.
Very little is known about the receptors and target molecules involved in natural killer (NK) cell activity. Here we present a model system in which interleukin-2-activated killing by NK cells depends on the intercellular adhesion molecule ICAM-2 and is regulated by the distribution of ICAM-2. The level of ICAM-2 expression in NK-sensitive and resistant cells is similar, but in sensitive cells ICAM-2 is concentrated into bud-like cellular projections known as uropods, whereas in resistant cells it is evenly distributed. The cytoskeletal-membrane linker protein ezrin is also localized in uropods. Transfection of human ezrin into NK-resistant cells induces uropods formation, redistribution of ICAM-2 and ezrin, and sensitizes target cells to interleukin-2-activated killing. These results reveal a new mechanism of target-cell recognition: cytotoxic cells recognize adhesion molecules that are already present on normal cells, but in diseased cells are concentrated into a biologically active cell-surface region by cytoskeletal reorganization. The results also highlight the importance of cytoskeletal interactions in the regulation of ICAM-2-mediated adhesive phenomena.
Animals↗