Dobrava Hantavirus Research Articles

Dobrava hantavirus causes hemorrhagic fever with renal syndrome in central Europe and is carried by two different Apodemus mice species

In central Europe, hemorrhagic fevers with renal syndrome (HFRS) in humans are caused by the hantavirus species Puumala (transmitted by voles) and a second, Hantaan-related species (transmitted by mice). The second virus could be identified as Dobrava virus. To date, 19 clinical cases of Dobrava infection have been found in Germany and Slovakia. All patients exhibited a mild/moderate clinical course and no case fatality occurred. Screening for infected rodents revealed that the striped field mouse (Apodemus agrarius) represents the main reservoir for Dobrava virus in central Europe. Nucleotide sequence comparisons and phylogenetic analysis based on complete and partial genomic S segment nucleotide sequences placed the Slovakian A. agrarius-derived hantavirus strains within the Dobrava species, forming a cluster on the Dobrava phylogenetic tree. In east Slovakia, a single Dobrava virus-infected yellow-necked mouse (Apodemus flavicollis) was trapped in a locality that predominantly showed Dobrava-infected A. agrarius. Comparison of the S segment sequence (nucleotides 381-935) revealed that the Dobrava strain from A. flavicollis shows only 84.3% nucleotide homology to A. agrarius-derived strains from this location but 96.3% homology to A. flavicollis-derived Dobrava strains from the Balkans (southeast Europe). Phylogenetic analysis of the partial S segment placed the A. flavicollis-derived Dobrava strain from Slovakia on a distinct Dobrava lineage (DOB-Af) together with the south-east European A. flavicollis-derived strains. The results indicate that Dobrava strains from A. agrarius (DOB-Aa) vs. A. flavicollis (DOB-Af) could develop different degrees of virulence in humans.

Dobrava hantavirus causes hemorrhagic fever with renal syndrome in central Europe and is carried by two different Apodemus mice species

In central Europe, hemorrhagic fevers with renal syndrome (HFRS) in humans are caused by the hantavirus species Puumala (transmitted by voles) and a second, Hantaan-related species (transmitted by mice). The second virus could be identified as Dobrava virus. To date, 19 clinical cases of Dobrava infection have been found in Germany and Slovakia. All patients exhibited a mild/moderate clinical course and no case fatality occurred. Screening for infected rodents revealed that the striped field mouse (Apodemus agrarius) represents the main reservoir for Dobrava virus in central Europe. Nucleotide sequence comparisons and phylogenetic analysis based on complete and partial genomic S segment nucleotide sequences placed the Slovakian A. agrarius-derived hantavirus strains within the Dobrava species, forming a cluster on the Dobrava phylogenetic tree. In east Slovakia, a single Dobrava virus-infected yellow-necked mouse (Apodemus flavicollis) was trapped in a locality that predominantly showed Dobrava-infected A. agrarius. Comparison of the S segment sequence (nucleotides 381–935) revealed that the Dobrava strain from A. flavicollis shows only 84.3% nucleotide homology to A. agrarius-derived strains from this location but 96.3% homology to A. flavicollis-derived Dobrava strains from the Balkans (southeast Europe). Phylogenetic analysis of the partial S segment placed the A. flavicollis-derived Dobrava strain from Slovakia on a distinct Dobrava lineage (DOB-Af) together with the south-east European A. flavicollis-derived strains. The results indicate that Dobrava strains from A. agrarius (DOB-Aa) vs. A. flavicollis (DOB-Af) could develop different degrees of virulence in humans. J. Med. Virol. 63:158–167, 2001. © 2001 Wiley-Liss, Inc.

Dobrava hantavirus causes hemorrhagic fever with renal syndrome in central Europe and is carried by two differentApodemus mice species

Dobrava hantavirus causes hemorrhagic fever with renal syndrome in central Europe and is carried by two differentApodemus mice species

Puumala and Dobrava hantaviruses causing hemorrhagic fever with renal syndrome in Estonia.

Puumala and Dobrava hantaviruses causing hemorrhagic fever with renal syndrome in Estonia.

Genetic analysis of wild-type Dobrava hantavirus in Slovenia: co-existence of two distinct genetic lineages within the same natural focus.

Genetic analysis was performed of wild-type (wt) Dobrava hantavirus (DOB) strains from Slovenia, the country where the virus was first discovered and where it was found to cause haemorrhagic fever with renal syndrome (HFRS), with a fatality rate of 12%. Two hundred and sixty mice of the genus APODEMUS:, trapped in five natural foci of DOB-associated HFRS during 1990-1996, were screened for the presence of anti-hantavirus antibodies and 49 APODEMUS: flavicollis and four APODEMUS: agrarius were found to be positive. RT-PCR was used to recover partial sequences of the wt-DOB medium (M) and small (S) genome segments from nine A. flavicollis and one A. agrarius. Sequence comparison and phylogenetic analysis of the Slovenian wt-DOB strains revealed close relatedness of all A. flavicollis-derived virus sequences (nucleotide diversity up to 6% for the M segment and 5% for the S segment) and the geographical clustering of genetic variants. In contrast, the strain harboured by A. agrarius showed a high level of genetic diversity from other Slovenian DOB strains (14%) and clustered together on phylogenetic trees with other DOB strains harboured by A. agrarius from Russia, Estonia and Slovakia. These findings suggest that the DOB variants carried by the two species of APODEMUS: in Europerepresent two distinct genetic lineages.

Antigenic properties and diagnostic potential of recombinant Dobrava virus nucleocapsid protein

Dobrava hantavirus (DOBV) causes severe hemorrhagic fever with renal syndrome in the Balkan region and has been detected recently also in Russia, Estonia, and Germany. DOBV nucleocapsid protein (N) was produced in insect cells, using the baculovirus expression system (bac-DOBV-N), and in E. coli as a truncated (aa 1-165) glutathione-S transferase fusion protein (DOBV-dN-GST). The antigenic properties of bac-DOBV-N were found identical to native DOBV-N when examined by a panel of hantavirus-specific monoclonal antibodies. Enzyme immunoassays for detection of IgM and IgG antibodies were set up using DOBV recombinant N proteins and compared with those based on recombinant Hantaan and Puumala virus N, using panels of sera collected from DOBV, Hantaan and Puumala virus-infected patients. Full-length N protein (bac-DOBV-N) was found to be a more sensitive antigen than DOBV-dN-GST. The sensitivity values for sera from DOBV-infected patients were 100% for bac-DOBV-N and 86% for DOBV-dN-GST by IgM assays, and 98% for bac-DOBV-N and 88% for DOBV-dN-GST by IgG assays. The specificity values were 100% for bac-DOBV-N and 99% for DOBV-dN-GST by IgM assays, and 100% for both antigens by IgG assays.

Short report: simultaneous occurrence of Dobrava, Puumala, and Tula Hantaviruses in Slovakia.

The prevalence of antibody to hantaviruses in Slovakia (serum panel n = 2,133) was lower in the western part (0.54%) and higher in the eastern part (1.91%) of the country and was found to be significantly enhanced in a group of forest workers from eastern Slovakia (5.88%). One-third of the IgM-negative convalescent phase sera from patients with hemorrhagic fever with renal syndrome exhibited antibodies reacting predominantly with Puumala virus antigen, while two-thirds had antibodies directed mainly against Hantaan virus antigen. Fine analysis of two Hantaan virus-reactive sera by a focus reduction neutralization test showed that Dobrava hantavirus was the source of these human infections. Initial results of rodent screening indicated the circulation of Dobrava virus in populations of striped field mice (Apodemus agrarius) in eastern Slovakia.

Dobrava virus infection: serological diagnosis and cross-reactions to other hantaviruses

Recent data have shown that Dobrava (DOB) hantavirus is the cause of severe haemorrhagic fever with renal syndrome (HFRS) in central and eastern Europe. To determine whether serological assays need to be based on the homologous viral antigen rather than on closely related hantavirus antigens, acute and convalescent sera from patients with HFRS collected in former Yugoslavia were examined for IgM and IgG to three hantavirus antigens; DOB, Hantaan (HTN) and Puumala (PUU). Focus reduction neutralization test was included for comparison and confirmation of the enzyme-linked immunosorbent assay (ELISA) results. Although the results showed that the cross-reactivity was high between these three antigens during the acute phase of the disease, one of 155 patients serum samples reacted only in the DOB antigen-based IgM assay. The evaluation of IgG reactivities revealed that a DOB antigen-based IgG ELISA has to be used in sero-epidemiological studies; 7.1% (11/155) of the acute phase/early convalescent sera and 12.5% (2/16) of the late convalescent sera, respectively, reacted only with the homologous DOB antigen.

A major outbreak of hantavirus infection in Belgium in 1995 and 1996.

Haemorrhagic fever with renal syndrome (HFRS) is a human disease characterized by flu-like symptoms, renal dysfunction, and in severe cases, haemorrhagic manifestations. The causative agents of HFRS are Hantaan (HTN), Seoul (SEO), Puumala (PUU) and Dobrava (DOB) hantaviruses. Hantavirus infections are of increasing importance in Europe. Outbreaks occur in Belgium with a 3- to 4-year interval with an increasing number of cases. We describe the largest outbreak so far in Belgium with 217 serologically and clinically confirmed cases in the period between October 1995 and December 1996. We demonstrated that the use of viral antigen derived from a local PUU-strain was able to detect significantly more sera positive for IgM in an immunofluorescence assay. Furthermore, although in some cases SEO, HTN and DOB antibody-reactivities were detected by ELISA, only PUU infections could be confirmed by neutralization test. The presence of an unknown hantavirus serotype circulating in Belgium should be considered.

Dobrava hantavirus in Russia

Dobrava hantavirus in Russia

Human Dobrava hantavirus infections in Estonia

Outbreaks of severe hemorrhagic fever with renal syndrome (HFRS) caused by Dobrava hantavirus (DOB) have been reported in Albania, Greece, and Bosnia-Herzegovina. A seroepidemiologic study conducted by the authors in Estonia provided the first evidence of human DOB infection in a Baltic country. Hantavirus infection was first confirmed in Estonia in 1986 and believed related to Puumala hantavirus (PUU). To enable precise serotyping, serum samples were collected from 1728 healthy people in 11 counties in Estonia. Of 51 samples confirmed as positive, 34 showed the highest reactivities to PUU, while 17 reacted best with DOB antigen. In a further analysis of 11 selected positive samples, six showed the presence of neutralizing antibodies specific to PUU and five reacted specifically with DOB. These findings suggest that both BOB and PUU cause human infections in Estonia.

Dobrava hantavirus outbreak in Russia

Dobrava hantavirus outbreak in Russia

Dobrava hantavirus in Estonia: does the virus exist throughout Europe?

Hantaviruses cause haemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). Each hantavirus is maintained in its own natural rodent host, and human beings get infected by inhalation of rodent excreta. 1 Plyusnin A Vapalahti O Vaheri A Hantaviruses: genome structure, expression and evolution. J Gen Virol. 1996; 77: 2677-2687 Crossref PubMed Scopus (345) Google Scholar HPS is caused by Sin Nombre and related viruses, which are carried by sigmodontine rodents endemic in the New World; HFRS is associated with Hantaan (HTN) and Seoul (SEO) viruses in Asia and with Puumala virus in Europe. 1 Plyusnin A Vapalahti O Vaheri A Hantaviruses: genome structure, expression and evolution. J Gen Virol. 1996; 77: 2677-2687 Crossref PubMed Scopus (345) Google Scholar Dobrava (DOB) virus has recently been shown to cause severe HFRS in Slovenia, Albania, Greece, and Bosnia. 2 Avsic-Zupanc T Toney A Anderson K et al. Genetic and antigenic properties of Dobrava virus: a unique member of the Hantavirus genus, family Bunyaviridae.. J Gen Virol. 1995; 76: 2801-2808 Crossref PubMed Scopus (86) Google Scholar , 3 Antoniades A Stylinakis A Papa A et al. Direct detection of Dobrava virus in Greek and Albanian haemorrhagic fever with renal syndrome (HFRS) patients. J Infect Dis. 1996; 174: 407-410 Crossref PubMed Scopus (90) Google Scholar , 4 Lundkvist A, Hukic M, Hörling J, et al. Puumala and Dobrava viruses cause haemorrhagic fever with renal syndrome in Bosnia-Herzegovina: evidence of highly cross-neutralising antibody responses in early patient sera. J Med Virol (in press). Google Scholar The prototype DOB strain was isolated from the yellow-necked field mouse, Apodemus flavicollis, in Slovenia.2 Avsic-Zupanc T Toney A Anderson K et al. Genetic and antigenic properties of Dobrava virus: a unique member of the Hantavirus genus, family Bunyaviridae.. J Gen Virol. 1995; 76: 2801-2808 Crossref PubMed Scopus (86) Google Scholar We report detection of DOB genome sequences in the striped field mouse, Apodemus agrarius, from Estonia.

Prevalence of Serum Antibodies to Hantaviruses in Northern Sweden as Measured by Recombinant Nucleocapsid Proteins

An enzyme-linked immunosorbent assay (ELISA) based on recombinant nucleocapsid protein (rN delta) (aa 1-117) of Hantaan, Seoul, Dobrava, Sin Nombre and Puumala hantaviruses was used to determine the prevalence of antibodies among randomized and stratified individuals from northern Sweden. In total, 137/1533 individuals (8.9%) had specific serum IgG antibodies to Puumala virus, the only hantavirus known to occur in the region. The prevalence of antibodies to Puumala virus (8.9%) was determined to be higher than previously reported (5.4%) in the same serum material, by use of immunofluorescence assay. As expected, sera reactive to Puumala virus rN delta did frequently cross-react with Sin Nombre virus protein. Unexpectedly, 21/1533 (1.4%) individuals recognized the Sin Nombre virus rN delta exclusively. Another 8 subjects showed reactivity in the ELISA to Hantaan, Seoul, or Dobrava virus-derived rN delta but not Puumala virus or Sin Nombre virus rN delta. The present demonstration in some individuals of antibodies specifically recognizing the Sin Nombre, Dobrava, Hantaan and Seoul virus protein justifies an awareness of the possibility that hantaviruses antigenically different from Puumala virus might occur in the region.