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tula virus: a newly detected hantavirus carried by european common voles.a novel hantavirus has been discovered in european common voles, microtus arvalis and microtus rossiaemeridionalis. according to sequencing data for the genomic rna s segment and nucleocapsid protein and data obtained by immunoblotting with a panel of monoclonal antibodies, the virus, designated tula virus, is a distinct novel member of the genus hantavirus. phylogenetic analyses of tula virus indicate that it is most closely related to prospect hill, puumala, and muerto canyon viruses. the resu ...19947966573
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 ...19968862399
unique and conserved features of tula hantavirus m gene encoding envelope glycoproteins g1 and g2.the sequence of the genomic m segment encoding the surface glycoproteins g1 and g2 of wild-type tula hantavirus (tul) has been determined. analyses of m nucleotide sequences show that tul is genetically distinct from other hantaviruses. comparison to ten currently known hantavirus g1g2 amino acid sequences points out several, presumably functional, regions with substantial homology indicating a common ancestry and similar evolutionary pathways for all members of the hantavirus genus.19968883363
characterization of tula virus antigenic determinants defined by monoclonal antibodies raised against baculovirus-expressed nucleocapsid protein.tula virus was recently discovered by rt-pcr in lung samples from european common voles (microtus arvalis and m. rossiaemeridionalis). since virus isolation attempts had been unsuccessful, no antigen was available for analysis or for use in immunoassays. to circumvent this, complete tula virus nucleocapsid protein (bac-tul-n) was expressed in recombinant baculovirus. rodent antibody end-point titers to bac-tul-n and to truncated n fragments indicated that the nh2-terminal region is the major ant ...19968896239
quasispecies in wild-type tula hantavirus populations.tula virus (tul) is a recently detected hantavirus carried by european common voles. reverse transcriptase pcr cloning was used to study tul s segment/n protein quasispecies. both the distribution and character of mutations observed in three mutant spectra indicated limited selection at the protein level. at least 8% of the mutations were neutral or well tolerated; fixation of such mutations may play a role in tul evolution in its natural host.19968971044
isolation and characterization of tula virus, a distinct serotype in the genus hantavirus, family bunyaviridae.a vero e6 cell culture isolate of tula virus (tul), a hantavirus first detected in european common voles (microtus arvalis and m. rossiaemeridionalis) by rt-pcr was obtained after initial passaging of tul-infected vole lung samples in laboratory-colonized m. arvalis. tul was defined as a classical serotype by a cross-focus-reduction neutralization test (frnt) and was also shown to be distinct from other hantaviruses by haemagglutination inhibition assay. the sequences of s, m and partial l genom ...19969000098
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
completion of the tula hantavirus genome sequence: properties of the l segment and heterogeneity found in the 3' termini of s and l genome rnas.in this study the l segment and the 5' and 3' termini of the s, m and l segments of the prototype tula hantavirus (tul) were sequenced, thus completing the first determination of the genome sequence of a hantavirus that has not been linked to any human disease. the tul l segment comprises 6541 nt with one orf of 6459 nt in the antigenome sense. this orf potentially encodes a 2153 aa protein with a predicted molecular mass of 247 kda. the amino acid sequence includes all the motifs conserved in r ...19989820136
recombination in tula hantavirus evolution: analysis of genetic lineages from slovakia.to examine the evolution of tula hantavirus (tul), carried by the european common vole (microtus arvalis and m. rossiaemeridionalis), we have analyzed genetic variants from slovakia, the country where the virus is endemic. phylogenetic analysis (phylip) based on either partial (nucleotides [nt] 441 to 898) or complete n-protein-encoding sequences divided slovakian tul variants into two main lineages: (i) strains from eastern slovakia, which clustered with russian strains, and (ii) strains from w ...19999847372
[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
interaction between molecules of hantavirus nucleocapsid protein.intermolecular interactions of tula hantavirus n (nucleocapsid) protein were detected in the yeast two-hybrid system, prompting further attempts to study this phenomenon. using chemical cross-linking and immunoblotting it was shown that the n protein from purified virus and from infected cell lysates as well as recombinant protein produced in a baculovirus expression system are capable of forming dimers, trimers and multimers, thus confirming the capacity of the protein molecules to interact wit ...200111457990
transfection-mediated generation of functionally competent tula hantavirus with recombinant s rna segment.since the discovery of rna recombination in polioviruses, there has been a general belief that this mechanism operates only in positive-sense rna viruses. recently, studying wild-type tula hantavirus, we observed a mosaic-like structure of the s rna segment that was consistent with generation by recombination between viruses from two genetic lineages. here we show transfection-mediated rescue of tula virus carrying recombinant s rna segment. independent attempts yielded s rna molecules of simila ...200211889055
tula hantavirus in belgium.european common voles (microtus arvalis), captured in belgium in 1999, were proven by molecular as well as by serological techniques to be infected with tula hantavirus (tulv). this is the first evidence for the presence of tulv in this country. no indication of spill-over infections of puumala virus, known to be highly endemic among bank voles (clethrionomys glareolus) within the same geographical regions as the trapped tulv-infected common voles, was observed. together with previous reports on ...200212002543
identification of tula hantavirus in pitymys subterraneus captured in the cacak region of serbia-yugoslavia.atypical serum neutralizing antibody responses to prototype strains of puumala viruses in some patients with hemorrhagic fever with renal syndrome (hfrs) have long suggested the existence of other hantaviruses in the balkans.200212044299
tula virus infection associated with fever and exanthema after a wild rodent bite.reported here is the first case of human acute infection with tula virus, which occurred in a 12-year-old boy in switzerland. this hantavirus had been considered apathogenic to humans, and in switzerland only tulv-genome sequences have been demonstrated in wild rodents to date. in this case, paronychia, fever and exanthema occurred after the patient was bitten by a wild rodent, indicating an unusual route of hantavirus transmission. thus, tula virus infection should be taken into account in pati ...200212072943
rodent host specificity of european hantaviruses: evidence of puumala virus interspecific spillover.in order to investigate rodent host specificity of european hantaviruses, experimental infection of colonized and wild-trapped rodents was performed. in addition to the natural rodent reservoir, clethrionomys glareolus, puumala hantavirus (puuv) could infect colonized microtus agrestis and lemmus sibiricus, but not syrian hamsters or balb/c mice. neither c. glareolus, nor m. agrestis, could be readily infected by tula hantavirus (tulv). wild-trapped apodemus flavicollis and a. agrarius, the natu ...200212376967
non-covalent interaction between nucleocapsid protein of tula hantavirus and small ubiquitin-related modifier-1, sumo-1.to find cellular binding counterparts for the nucleocapsid protein (n) of tula hantavirus (tulv), two cdna libraries were screened using yeast two-hybrid systems based on lexa and gal4 transcription factors. five cdna clones encoding sumo-1 (small ubiquitin-related modifier, also known as sentrin) were selected in the lexa system. confocal microscopy revealed that, in infected cells, tulv n protein and sumo-1 colocalize at the perinuclear area providing further evidence for interaction between t ...200312606074
genetic evidence for tula virus in microtus arvalis and microtus agrestis populations in croatia.to determine the threat of hantavirus infection to u.s. forces, small mammals were sampled from training areas within croatia. of the 152 samples, 20 were positive for tula virus (tul), 12 common voles (microtus arvalis) and eight field voles (microtus agrestis). sequences from m. agrestis were found in five and sequences from m. arvalis were found in six of seven sequence groups. the high percentage of the same tul sequences in m. agrestis and m. arvalis suggests the co-occurrence of this virus ...200212656127
human tula virus infection or rat-bite fever? 200312736795
mapping of the regions involved in homotypic interactions of tula hantavirus n protein.hantavirus nucleocapsid (n) protein has been suggested to form homodimers and homotrimers that are further integrated into the nucleocapsid filaments around the viral rna. here we report detailed mapping of the regions involved in the homotypic n protein interactions in tula hantavirus (tulv). peptide scan screening was used to define the interaction regions, and the mammalian two-hybrid assay was used for the functional analysis of n protein mutants. to study linear regions responsible for n pr ...200314512541
occurrence of renal and pulmonary syndrome in a region of northeast germany where tula hantavirus circulates.hantavirus species tula (tulv) is carried by european common voles (microtus spp.). its pathogenic potential for humans is unknown. in a rural region of northeast germany, a 43-year-old man became ill with fever, renal syndrome, and pneumonia. typing of late acute- and convalescent-phase sera by focus reduction neutralization assay revealed the presence of neutralizing antibodies against tulv. moreover, we detected tulv genetic material in microtus arvalis animals that were trapped at places onl ...200314532254
tula hantavirus l protein is a 250 kda perinuclear membrane-associated protein.the complete open reading frame of tula hantavirus (tulv) l rna was cloned in three parts. the middle third (nt 2191-4344) could be expressed in e. coli and was used to immunize rabbits. the resultant antiserum was then used to immunoblot concentrated tulv and infected vero e6 cells. the l protein of a hantavirus was detected, for the first time, in infected cells and was found to be expressed as a single protein with an apparent molecular mass of 250 kda in both virions and infected cells. usin ...200415105534
differential antiviral response of endothelial cells after infection with pathogenic and nonpathogenic hantaviruses.hantaviruses represent important human pathogens and can induce hemorrhagic fever with renal syndrome (hfrs), which is characterized by endothelial dysfunction. both pathogenic and nonpathogenic hantaviruses replicate without causing any apparent cytopathic effect, suggesting that immunopathological mechanisms play an important role in pathogenesis. we compared the antiviral responses triggered by hantaan virus (htnv), a pathogenic hantavirus associated with hfrs, and tula virus (tulv), a rather ...200415163707
[prevalence of hantavirus infections in germany].hantaviruses belong to the group of "emerging" viruses. pathogenic european hantaviruses can cause a human disease designated "hemorrhagic fever with renal syndrome" of varying severity. in general, diagnostics of hantavirus infections are based on immunofluorescence assays using virus-infected cells or enzyme immunoassays and western blot tests using recombinant nucleocapsid proteins. for highly sensitive detection of hantavirus-specific antibodies in the enzyme immunoassay, a homologous hantav ...200415254821
characterization of tula virus from common voles (microtus arvalis) in poland: evidence for geographic-specific phylogenetic clustering.tula virus (tulv), a recently identified arvicolid rodent-borne hantavirus, is harbored by the european common vole (microtus arvalis) in central russia and the czech and slovak republics. we report the isolation and characterization of this hantavirus from m. arvalis captured in poland, a country where human disease caused by hantaviruses has not been recognized. of 34 arvicolid rodents (24 clethrionomys glareolus, 9 m. arvalis, 1 pitymys sp.) captured in lodz and tuszyn, poland, during june to ...200415284484
tula hantavirus infection of vero e6 cells induces apoptosis involving caspase 8 activation.hantaviruses are known to cause two severe human diseases: haemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome. the mechanisms of pathogenesis of these two diseases are progressively becoming understood. recently, two hantaviruses, hantaan and prospect hill were reported to cause programmed cell death of vero e6 cells. this study shows that tula hantavirus (tulv) infection efficiently triggers an apoptotic programme in infected vero e6 cells, and that the replication of tulv ...200415483239
oligomerization of hantavirus n protein: c-terminal alpha-helices interact to form a shared hydrophobic space.the structure of the nucleocapsid protein of bunyaviruses has not been defined. earlier we have shown that tula hantavirus n protein oligomerization is dependent on the c-terminal domains. of them, the helix-loop-helix motif was found to be an essential structure. computer modeling predicted that oligomerization occurs via helix protrusions, and the shared hydrophobic space formed by amino acids residues 380-iillf-384 in the first helix and 413-li-414 in the second helix is responsible for stabi ...200415564476
tula hantavirus triggers pro-apoptotic signals of er stress in vero e6 cells.tula virus is a member of the hantavirus genus of the family bunyaviridae. viruses of this family have an unusual pattern of intracellular maturation at the er-golgi compartment. we recently found that tula virus, similar to several other hantaviruses, is able to induce apoptosis in cultured cells [li, x.d., kukkonen, s., vapalahti, o., plyusnin, a., lankinen, h., vaheri, a., 2004. tula hantavirus infection of vero e6 cells induces apoptosis involving caspase 8 activation. j. gen. virol. 85, 326 ...200515708603
recombinant tula hantavirus shows reduced fitness but is able to survive in the presence of a parental virus: analysis of consecutive passages in a cell culture.tula hantavirus carrying recombinant s rna segment (rectulv) grew in a cell culture to the same titers as the original cell adapted variant but presented no real match to the parental virus. our data showed that the lower competitiveness of rectulv could not be increased by pre-passaging in the cell culture. nevertheless, the recombinant virus was able to survive in the presence of the parental virus during five consecutive passages. the observed survival time seems to be sufficient for transmis ...200515725355
hfrs causing hantaviruses do not induce apoptosis in confluent vero e6 and a-549 cells.hantaviruses are known to cause little or no cytopathic effect in vitro, but have been suggested to cause apoptosis. to determine whether different hantaviruses would induce apoptosis to varying degrees, confluent vero e6 cells were infected with the hemorrhagic fever with renal syndrome (hfrs) causing viruses hantaan, dobrava, saaremaa, and puumala. however, no difference was found in the percentage of adherent cells, or of cells with condensed nuclei, between non-infected and virus-infected ce ...200515834879
[the epizootological and virological characteristics of a natural hantavirus infection focus in the subtropic zone of the krasnodarsk territory].a natural focus of hantavirus infection was detected and examined during the studies conducted in 2000-2002 around the sochi (the western spurs of the great caucasus ridge, which descended to the black sea (the krasnodar territory of russia). at least 4 rodent species, such as microtus majori, a. (s.) ponticus, a. agrarius, a. (s.) ciscaucasicus, were shown to participate in the circulation of hantaviruses. a comparative analysis of the nucleotide sequences of genomic s- and m-segments of hantav ...200516078428
a novel method for cloning of non-cytolytic viruses.hantaviruses are rodent-borne pathogens with a segmented single-stranded rna genome of negative polarity. spontaneous occurrence of variants with genetic heterogeneity have been observed both in vivo and in vitro. the objective of this study was to establish a method for the cloning of genetically homogenous hantaviruses which can be used for subsequent functional studies. infected veroe6 cells were incubated with an agarose/medium overlay to prevent uncontrolled distribution of de novo synthesi ...200616504312
oligomerization of hantavirus nucleocapsid protein: analysis of the n-terminal coiled-coil domain.hantaviruses constitute a genus in the family bunyaviridae. they are enveloped negative-strand rna viruses with a tripartite genome encoding the nucleocapsid (n) protein, the two surface glycoproteins gn and gc, and an rna-dependent rna polymerase. the n protein is the most abundant component of the virion; it encapsidates genomic rna segments forming ribonucleoproteins and participates in genome transcription and replication as well as virus assembly. in the course of rna encapsidation, n prote ...200616940519
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 100-1 ...200616972031
[epizootology of hemorrhagic fever with renal syndrome in the central chernozem region].a total of 5149 small mammals belonging to 16 species were collected from the lipetsk, voronezh, and belgorod regions (40 administrative districts) in 2003-2004 and examined by elisa and ifa to detect hantavirus antigen and antibodies in the lung tissues. hantavirus circulation was revealed in 13 species, the highest hantavirus activity being detected in field (apodemus agrarius) and small wood (a. (s) uralensis) mice (dobrava-belgrad virus), bank (clethrionomis glareolus) (puumala virus) and co ...200617087062
chemokine production predominates in human monocytes infected with tula virus.many reports suggest the hypothesis of a complex immune response accompanying hantaviral infections. however, little is known about the immunopathogenesis of nonpathogenic hantaviruses, especially tula virus (tulv). the aim of our study was to determine the cytokine/chemokine profile induced after the infection of human macrophages with tulv and the role of viral replication in this process. also, we wanted to establish how the study of tulv is relevant to our previous study of pathogenic hantav ...200717425435
tula and puumala hantavirus nss orfs are functional and the products inhibit activation of the interferon-beta promoter.the s rna genome segment of hantaviruses carried by arvicolinae and sigmodontinae rodents encodes the nucleocapsid (n) protein and has an overlapping (+1) open reading frame (orf) for a putative nonstructural protein (nss). the aim of this study was to determine whether the orf is functional. a protein corresponding to the predicted size of tula virus (tulv) nss was detected using coupled in vitro transcription and translation from a cloned s segment cdna, and a protein corresponding to the pred ...200717705180
detection and typing of human pathogenic hantaviruses by real-time reverse transcription-pcr and pyrosequencing.because the clinical course of human infections with hantaviruses can vary from subclinical to fatal, rapid and reliable detection of hantaviruses is essential. to date, the diagnosis of hantavirus infection is based mainly on serologic assays, and the detection of hantaviral rna by the commonly used reverse transcription (rt)-pcr is difficult because of high sequence diversity of hantaviruses and low viral loads in clinical specimens.200717717126
kinship, dispersal and hantavirus transmission in bank and common voles.hantaviruses are among the main emerging infectious agents in europe. their mode of transmission in natura is still not well known. in particular, social features and behaviours could be crucial for understanding the persistence and the spread of hantaviruses in rodent populations. here, we investigated the importance of kinclustering and dispersal in hantavirus transmission by combining a fine-scale spatiotemporal survey (4 km2) and a population genetics approach. two specific host-hantavirus s ...200818071626
tula hantavirus isolate with the full-length orf for nonstructural protein nss survives for more consequent passages in interferon-competent cells than the isolate having truncated nss orf.the competitiveness of two tula hantavirus (tulv) isolates, tulv/lodz and tulv/moravia, was evaluated in interferon (ifn) -competent and ifn-deficient cells. the two isolates differ in the length of the open reading frame (orf) encoding the nonstructural protein nss, which has previously been shown to inhibit ifn response in infected cells.200818190677
[molecular characterization of hantavirus zhejiang isolate zt10 strain from m. fartis].to learn about the complete genomic sequence of the seoul virus strain zt10 isolated from m. fartis.200818414685
high rates of molecular evolution in hantaviruses.hantaviruses are rodent-borne bunyaviruses that infect the arvicolinae, murinae, and sigmodontinae subfamilies of muridae. the rate of molecular evolution in the hantaviruses has been previously estimated at approximately 10(-7) nucleotide substitutions per site, per year (substitutions/site/year), based on the assumption of codivergence and hence shared divergence times with their rodent hosts. if substantiated, this would make the hantaviruses among the slowest evolving of all rna viruses. how ...200818417484
oligomerization of hantaviral nucleocapsid protein: charged residues in the n-terminal coiled-coil domain contribute to intermolecular interactions.the nucleocapsid (n) protein of hantaviruses (family bunyaviridae) is the most abundant component of the virion; it encapsidates genomic rna segments and participates in viral genome transcription and replication, as well as in virus assembly. during rna encapsidation, the n protein forms intermediate trimers and then oligomers via 'head-to-head, tail-to-tail' interactions. in previous work, using tula hantavirus (tulv) n protein as a model, it was demonstrated that an intact coiled-coil structu ...200818753226
hantaviruses and tnf-alpha act synergistically to induce erk1/2 inactivation in vero e6 cells.we have previously reported that the apathogenic tula hantavirus induces apoptosis in vero e6 epithelial cells. to assess the molecular mechanisms behind the induced apoptosis we studied the effects of hantavirus infection on cellular signaling pathways which promote cell survival. we previously also observed that the tula virus-induced cell death process is augmented by external tnf-alpha. since tnf-alpha is involved in the pathogenesis of hantavirus-caused hemorrhagic fever with renal syndrome ...200818822184
first detection of tula hantaviruses in microtus arvalis voles in hungary.tula hantavirus (tulv) is a member of the genus hantavirus, family bunyaviridae and is mainly carried by the european common vole (microtus arvalis). in order to detect tulv, we tested microtus arvalis (mar) and microtus subterraneus (msu) voles captured in two different locations of the southern transdanubian region of hungary. the viral genome was detectable in 37% of the tested mar voles but, interestingly, was absent in all msu. phylogenetic analysis performed with a partial coding sequence ...200818836679
first genetic detection of tula hantavirus in wild rodents in the netherlands. 200818977537
first molecular evidence of tula hantavirus in microtus voles in slovenia.different microtus species, present in a worldwide range habitat populating north america, europe, asia, and few other species have been recognized previously as a hantavirus reservoir. tula hantavirus was first reported in microtus arvalis and microtus rossiaemeridionalis from central russia and later discovered in several european countries. using molecular techniques we have demonstrated the presence of tula hantavirus in three different microtus species in slovenia. phylogenetic analyses of ...200919410611
new genetic lineage of tula hantavirus in microtus arvalis obscurus in eastern kazakhstan.genomic sequences of tula (tulv) hantavirus were recovered from tissue samples of european common voles microtus arvalis (subspecies obscurus) captured in kazakhstan, central asia. phylogenetic analysis of the s genomic segment of kazakh tulv strains showed that they form distinct, well supported genetic lineage and share a more ancient common ancestor with two russian lineages of tulv. the deduced sequence of the nucleocapsid (n) protein of kazakh tulv strains carried specific amino acid signat ...200819440462
degradation and aggresome formation of the gn tail of the apathogenic tula hantavirus.the cytoplasmic tails of envelope glycoprotein gn of pathogenic hantaviruses but not of the apathogenic prospect hill virus (phv) were recently reported to be proteasomally degraded in simian cos7 cells. here, we show that the cytoplasmic tails of the glycoproteins of the apathogenic hantaviruses tula virus (tulv) and phv are also degraded through the ubiquitin-proteasome pathway, both in human hek-293 and in simian vero e6 cells. tulv gn tails formed aggresomes in cells with proteasomal inhibit ...200919675185
extensive host sharing of central european tula virus.to examine the host association of tula virus (tulv), a hantavirus present in large parts of europe, we investigated a total of 791 rodents representing 469 microtus arvalis and 322 microtus agrestis animals from northeast, northwest, and southeast germany, including geographical regions with sympatric occurrence of both vole species, for the presence of tulv infections. based on serological investigation, reverse transcriptase pcr, and subsequent sequence analysis of partial small (s) and mediu ...201019889769
tula hantavirus nss protein accumulates in the perinuclear area in infected and transfected cells.the small rna segment of some hantaviruses (family bunyaviridae) encodes two proteins: the nucleocapsid protein and, in an overlapping reading frame, a non-structural (nss) protein. the hantavirus nss protein, like those of orthobunya- and phleboviruses, counteracts host innate immunity. here, for the first time, the nss protein of a hantavirus (tula virus) has been observed in infected cells and shown to localize in the perinuclear area. transiently expressed nss protein showed similar localiza ...201019956987
different cross-reactivity of human and rodent sera to tula virus and puumala virus.tula virus (tulv) and puumala virus (puuv) are hantaviruses carried by the bank vole (myodes glareolus) and european common vole (microtus arvalis), respectively. puuv is a causative agent of hemorrhagic fever with renal syndrome (hfrs), while tulv is thought to be apathogenic to humans. the n-terminal regions of the n proteins from tulv and puuv were expressed and applied as enzyme-linked immunosorbent assay (elisa) antigens. colonized japanese grass voles (microtus montebelli) and balb/c mice ...201020116854
pathogenic hantaviruses direct the adherence of quiescent platelets to infected endothelial cells.hantavirus infections are noted for their ability to infect endothelial cells, cause acute thrombocytopenia, and trigger 2 vascular-permeability-based diseases. however, hantavirus infections are not lytic, and the mechanisms by which hantaviruses cause capillary permeability and thrombocytopenia are only partially understood. the role of beta(3) integrins in hemostasis and the inactivation of beta(3) integrin receptors by pathogenic hantaviruses suggest the involvement of hantaviruses in altere ...201020181715
electron cryotomography of tula hantavirus suggests a unique assembly paradigm for enveloped viruses.hantaviruses (family bunyaviridae) are rodent-borne emerging viruses that cause a serious, worldwide threat to human health. hantavirus diseases include hemorrhagic fever with renal syndrome and hantavirus cardiopulmonary syndrome. virions are enveloped and contain a tripartite single-stranded negative-sense rna genome. two types of glycoproteins, g(n) and g(c), are embedded in the viral membrane and form protrusions, or "spikes." the membrane encloses a ribonucleoprotein core, which consists of ...201020219926
tula virus in populations of small terrestrial mammals in a rural landscape.over 5 years (2000-2004), populations of small mammals from a rural landscape in southern moravia (czech republic) were investigated for the presence of tula virus (tulv) antigen using the elisa set hantagnost. in total, 1566 individuals from 10 species were examined. the prevalence in the common vole (microtus arvalis pallas 1778), the main reservoir of tulv, was 10% (n = 871). the prevalence of tulv antigen increases with its population numbers. the highest number of tulv antigen-positive comm ...201020420534
cytoplasmic tails of hantavirus glycoproteins interact with the nucleocapsid protein.here we characterize the interaction between the glycoproteins (gn and gc) and the ribonucleoprotein (rnp) of puumala virus (puuv; genus hantavirus, family bunyaviridae). the interaction was initially established with native proteins by co-immunoprecipitating puuv nucleocapsid (n) protein with the glycoprotein complex. mapping of the interaction sites revealed that the n protein has multiple binding sites in the cytoplasmic tail (ct) of gn and is also able to bind to the predicted ct of gc. the ...201020444994
pathogenic hantaviruses andes virus and hantaan virus induce adherens junction disassembly by directing vascular endothelial cadherin internalization in human endothelial cells.hantaviruses infect endothelial cells and cause 2 vascular permeability-based diseases. pathogenic hantaviruses enhance the permeability of endothelial cells in response to vascular endothelial growth factor (vegf). however, the mechanism by which hantaviruses hyperpermeabilize endothelial cells has not been defined. the paracellular permeability of endothelial cells is uniquely determined by the homophilic assembly of vascular endothelial cadherin (ve-cadherin) within adherens junctions, which ...201020463083
non-human primates in outdoor enclosures: risk for infection with rodent-borne hantaviruses.different species of non-human primates have been exploited as animal disease models for human hantavirus infections. to study the potential risk of natural hantavirus infection of non-human primates, we investigated serum samples from non-human primates of three species living in outdoor enclosures of the german primate center (gpc), göttingen, located in a hantavirus endemic region of central germany. for that purpose we used serological assays based on recombinant antigens of the bank vole (m ...201120727685
andes virus regulation of cellular micrornas contributes to hantavirus-induced endothelial cell permeability.hantaviruses infect human endothelial cells (ecs) and cause two diseases marked by vascular permeability defects, hemorrhagic fever with renal syndrome (hfrs) and hantavirus pulmonary syndrome (hps). vascular permeability occurs in the absence of ec lysis, suggesting that hantaviruses alter normal ec fluid barrier functions. ecs infected by pathogenic hantaviruses are hyperresponsive to vascular endothelial growth factor (vegf), and this alters the fluid barrier function of ec adherens junctions ...201020844033
structural studies of hantaan virus.hantaan virus is the prototypic member of the hantavirus genus within the family bunyaviridae and is a causative agent of the potentially fatal hemorrhagic fever with renal syndrome. the bunyaviridae are a family of negative-sense rna viruses with three-part segmented genomes. virions are enveloped and decorated with spikes derived from a pair of glycoproteins (gn and gc). here, we present cryo-electron tomography and single-particle cryo-electron microscopy studies of hantaan virus virions. we ...201021068243
the c-terminal 42 residues of the tula virus gn protein regulate interferon induction.hantaviruses primarily infect the endothelial cell lining of capillaries and cause two vascular permeability-based diseases. the ability of pathogenic hantaviruses to regulate the early induction of interferon determines whether hantaviruses replicate in endothelial cells. tula virus (tulv) and prospect hill virus (phv) are hantaviruses which infect human endothelial cells but fail to cause human disease. phv is unable to inhibit early interferon (ifn) responses and fails to replicate within hum ...201121367904
seroprevalence study in forestry workers of a non-endemic region in eastern germany reveals infections by tula and dobrava-belgrade hantaviruses.highly endemic and outbreak regions for human hantavirus infections are located in the southern, southeastern, and western parts of germany. the dominant hantavirus is the bank vole transmitted puumala virus (puuv). in the eastern part of germany, previous investigations revealed tula virus (tulv) and dobrava-belgrade virus (dobv) infections in the respective rodent reservoirs. here, we describe a seroprevalence study in forestry workers from brandenburg, eastern germany, using igg elisa and imm ...201121611907
multiple infections of rodents with zoonotic pathogens in austria.rodents are important reservoirs for a large number of zoonotic pathogens. we examined the occurrence of 11 viral, bacterial, and parasitic agents in rodent populations in austria, including three different hantaviruses, lymphocytic choriomeningitis virus, orthopox virus, leptospira spp., borrelia spp., rickettsia spp., bartonella spp., coxiella burnetii, and toxoplasma gondii. in 2008, 110 rodents of four species (40 clethrionomys glareolus, 29 apodemus flavicollis, 26 apodemus sylvaticus, and ...201424915446
hypoxia induces permeability and giant cell responses of andes virus-infected pulmonary endothelial cells by activating the mtor-s6k signaling pathway.andes virus (andv) is a south american hantavirus that causes a highly lethal hantavirus pulmonary syndrome (hps) characterized by hypoxia, thrombocytopenia, and vascular leakage leading to acute pulmonary edema. andv infects human pulmonary microvascular and lymphatic endothelial cells (mecs and lecs, respectively) and nonlytically enhances the permeability of interendothelial cell adherence junctions in response to vascular endothelial growth factor (vegf). recent findings also indicate that a ...201324067973
infection of human airway epithelial cells by different subtypes of dobrava-belgrade virus reveals gene expression patterns corresponding to their virulence potential.dobrava-belgrade virus (dobv) is a pathogen causing hemorrhagic fever with renal syndrome in europe. virulence and case fatality rate are associated with virus genotype; however the reasons for these differences are not well understood. in this work we present virus-specific effects on the gene expression profiles of human lung epithelial cells (a549) infected with different genotypes of dobv (dobrava, kurkino, and sochi), as well as the low-virulent tula virus (tulv). the data was collected by ...201627058765
[human hantavirus diseases - still neglected zoonoses?].hantavirus disease is the most common rodent-borne viral infection in the czech republic, with a mean annual incidence of 0.02 cases per 100 000 population and specific antibodies detected in 1% of the human population. four hantaviruses (puumala, dobrava-belgrade, tula, and seewis) circulate in this country, of which puumala virus (responsible for a mild form of hemorrhagic fever with renal syndrome called nephropathia epidemica) and dobrava-belgrade virus (causing haemorrhagic fever with renal ...201526795222
surveillance of hantaviruses in poland: a study of animal reservoirs and human hantavirus disease in subcarpathia.the first cluster of hemorrhagic fever with renal syndrome (hfrs) in poland was identified in 2007 in the subcarpathian region. the natural environment of this area is a key habitat for hantavirus vectors. the animal reservoir of existing human hfrs clusters was studied to assess the occurrence of viruses (including tula virus, puumala virus, and dobrava-belgrade virus) among rodents. we examined 70 suspected human cases with symptoms corresponding to the clinical picture of hfrs. serological an ...201424902039
genetic detection of dobrava-belgrade hantavirus in the edible dormouse (glis glis) in central serbia.hantaviruses are endemic in the balkans, particularly in serbia, where sporadic cases and/or outbreaks of hantaviral human disease have been reported repeatedly, and evidenced serologically. here, we present genetic detection of dobrava-belgrade virus (dobv) hantaviral sequences in wild rodents trapped in central serbia. all the animals were pre-screened serologically by indirect immunofluorescence (if) test and only those with a positive finding of hantaviral antigens were further tested by pol ...201524762257
[hantaviruses in germany: threat for zoo, pet, companion and farm animals?].hantaviruses are so-called "emerging" and "re-emerging" viruses because of the new and sudden nature of their appearance. human infections can lead to two distinct disease patterns, the haemorrhagic fever with renal syndrome and the hantavirus cardiopulmonary syndrome. all known human pathogenic hantaviruses are transmitted through rodent hosts. there are three rodent-associated hantaviruses in germany. the bank vole-associated puumala virus (puuv) is responsible for most of the human hantavirus ...201424511827
phylogeographic diversity of pathogenic and non-pathogenic hantaviruses in slovenia.slovenia is a very diverse country from a natural geography point of view, with many different habitats within a relatively small area, in addition to major geological and climatic differences. it is therefore not surprising that several small mammal species have been confirmed to harbour hantaviruses: a. flavicollis (dobrava virus), a. agrarius (dobrava virus-kurkino), m. glareolus (puumala virus), s. areanus (seewis virus),m. agrestis, m. arvalis and m. subterraneus (tula virus). three of the ...201324335778
isolation and complete genome characterization of novel reassortant orthoreovirus from common vole (microtus arvalis).a novel mammalian orthoreovirus (mrv) strain was isolated from the lung tissue of a common vole (microtus arvalis) with tula hantavirus infection. seven segments (l1-l3, m2-m3, s2, and s4) of the hungarian mrv isolate morv/47ma/06 revealed a high similarity with an mrv strain detected in bank vole (myodes glareolus) in germany. the m1 and s3 segment of the hungarian isolate showed the closest relationship with the sequence of a slovenian human and a french murine isolate, respectively. the highe ...201727858312
high prevalence of tula hantavirus in common voles in the netherlands.tula virus (tulv) is a zoonotic hantavirus. knowledge about tulv in the netherlands is very scarce. therefore in 2014, 49 common voles (microtus arvalis) from a region in the south of the netherlands, and in 2015, 241 common voles from regions in the north of the netherlands were tested with the tulv quantitative rt-pcr. in the southern region, prevalence of tulv was 41% (20/49). in the northern regions, prevalence ranged from 12% (4/34) to 45% (17/38). phylogenetic analysis of the obtained sequ ...201728112627
hantavirus in new geographic regions, sweden.in sweden, human cases of puumala hantavirus (puuv) infections are reported from the northern endemic regions. we found hantavirus-specific antibodies in yellow-necked mice (apodemus flavicollis) trapped in human dwellings in the surroundings of the cities of uppsala and stockholm, which are situated far south from the traditional endemic areas of puuv. because the yellow-necked mouse is the most common rodent in human dwellings, hantaviruses in this rodent species may be important for the publi ...201627258208
a molecular-level account of the antigenic hantaviral surface.hantaviruses, a geographically diverse group of zoonotic pathogens, initiate cell infection through the concerted action of gn and gc viral surface glycoproteins. here, we describe the high-resolution crystal structure of the antigenic ectodomain of gn from puumala hantavirus (puuv), a causative agent of hemorrhagic fever with renal syndrome. fitting of puuv gn into an electron cryomicroscopy reconstruction of intact gn-gc spike complexes from the closely related but non-pathogenic tula hantavir ...201627117403
three vole species and one (?) novel arvicolid hantavirus pathogen: tula virus revisited. 201626794642
high genetic structuring of tula hantavirus.tula virus (tulv) is a vole-associated hantavirus with low or no pathogenicity to humans. in the present study, 686 common voles (microtus arvalis), 249 field voles (microtus agrestis) and 30 water voles (arvicola spec.) were collected at 79 sites in germany, luxembourg and france and screened by rt-pcr and tulv-igg elisa. tulv-specific rna and/or antibodies were detected at 43 of the sites, demonstrating a geographically widespread distribution of the virus in the studied area. the tulv prevale ...201626831932
tula hantavirus infection in a hospitalised patient, france, june 2015.we report an infection with tula virus in june 2015, leading to hospitalisation, in a patient living approximately 60 km east of paris with no previous remarkable medical history. clinical symptoms were limited to a fever syndrome with severe headache. the main laboratory findings included thrombocytopenia and elevated transaminase levels. based on s (small) gene sequence analysis, the strain affecting the patient was closely related to strains detected in central europe, especially to a south-e ...201526691901
[tula hantavirus in crimea].genetic evidence of the tula virus (tulv) in crimea region of russia is presented. based on the reverse transcription pcr and subsequent sequence analysis, a total of 4 rna isolates of the tulv were identified from the tissue samples of the altai voles microtus obscurus captured in the bakhchisaray district of the republic crimea. phylogenetic analysis of the s-, m-, and l-segment sequences of the crimean tulv strains showed that they formed distinct genetic lineage, russia iv, in the tulv varia ...201527192820
adler hantavirus, a new genetic variant of tula virus identified in major's pine voles (microtus majori) sampled in southern european russia.although at least 30 novel hantaviruses have been recently discovered in novel hosts such as shrews, moles and even bats, hantaviruses (family bunyaviridae, genus hantavirus) are primarily known as rodent-borne human pathogens. here we report on identification of a novel hantavirus variant associated with a rodent host, major's pine vole (microtus majori). altogether 36 hantavirus pcr-positive major's pine voles were identified in the krasnodar region of southern european russia within the years ...201525433134
tula hantavirus infection in immunocompromised host, czech republic.we report molecular evidence of tula hantavirus as an etiologic agent of pulmonary-renal syndrome in an immunocompromised patient. acute hantavirus infection was confirmed by using serologic and molecular methods. sequencing revealed tula virus genome rna in the patient's blood. this case shows that tula virus can cause serious disease in humans.201324209605
evidence of recombination in tula virus strains from serbia.tula hantavirus (tulv) belongs to bunyaviridae family, with negative sense rna genome. segmented nature of hantaviral genome allows for genetic reassortment, but the evidence of homologous recombination also exists. in this study we analyzed tulv sequences isolated in serbia on different occasions and from different rodent hosts: 1987 strain from microtus subterraneus and 2007 strain from microtus arvalis. phylogenetic analysis of both l and s segment sequences is suggestive of geographically re ...201424008094
tula virus infections in the eurasian water vole in central europe.recent reports of novel hantaviruses in shrews and moles and the detection of rodent-borne hantaviruses in different rodent species raise important questions about their host range and specificity, evolution, and host adaptation. tula virus (tulv), a european hantavirus, is believed to be slightly or non-pathogenic in humans and was initially detected in the common vole microtus arvalis, the east european vole m. levis (formerly rossiaemeridionalis), and subsequently in other microtus species. h ...201222225425
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