Dobrava-Belgrade virus (DOBV) is a European hanta-virus that causes hemorrhagic fever with renal syndrome (HFRS); case-fatality rates in Balkan countries are as high as 12%. To determine causative agents, we examined 126 cases of DOBV-associated HFRS in central and southern European Russia. In central Russia (Lipetsk, Voronezh, Orel regions), outbreaks were caused by a DOBV variant (DOBV-Aa) carried by Apodemus agrarius. In southern Russia (Sochi district), where HFRS is endemic, HFRS cases were caused by a new DOBV variant (DOBV-Ap), found in A. ponticus, a novel hantavirus natural host. Both viruses, DOBV-Aa/Lipetsk and DOBV-Ap/Sochi, were isolated through Vero E6 cells, genetically characterized, and used for serotyping of the HFRS patients' serum. The clinical severity of HFRS caused by DOBV-Aa resembles that of HFRS caused by Puumala virus (mild to moderate); clinical severity of disease caused by DOBV-Ap infections is more often moderate to severe.

Dobrava-Belgrade virus (DOBV) is a human pathogen that has evolved in, and is hosted by, mice of several species of the genus Apodemus. We propose a subdivision of the species Dobrava-Belgrade virus into four related genotypes – Dobrava, Kurkino, Saaremaa, and Sochi – that show characteristic differences in their phylogeny, specific host reservoirs, geographical distribution, and pathogenicity for humans.

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In Russia, 131,590 cases of hemorrhagic fever with renal syndrome caused by 6 different hantaviruses were reported during 2000–2017. Most cases, 98.4%, were reported in western Russia. The average case-fatality rate was 0.4%, and strong regional differences were seen, depending on the predominant virus type.

Epidemiological and ecological data of a Hantavirus infected bank vole population were collected using live-trapping methods. A close association between the distribution of HV-infected bank voles and wet habitat types was found. Several seroconversions were observed during the life of individual bank voles. All seroconversions occurred within the wet habitat types and only after a certain age was reached. Survival of HV-infected bank voles did not differ from not-infected animals. In the laboratory passive antibody transfer was observed from antibody-positive females to their offspring.

A large outbreak of hemorrhagic fever with renal syndrome (HFRS) occurred in the winter of 2006-2007 in a region southeast of Moscow in Central European Russia. Of the 422 patients with HFRS investigated in this study, 58 patients were found to be infected by Puumala virus, whereas as many as 364 were infected by Dobrava-Belgrade virus (DOBV). Early serum samples from 10 DOBV-infected patients were used for nucleic acid amplification, which was successful for 5 patients. Molecular analyses demonstrated that the causative hantavirus belongs to the DOBV-Aa genetic lineage, which is carried by the striped field mouse (Apodemus agrarius) as the natural reservoir host. Neutralization assays with convalescent-phase sera from these patients confirmed infection by DOBV-Aa; related viruses, such as the Dobrava-Slovenia virus (DOBV-Af) and the Dobrava-Sochi virus (DOBV-Ap), were neutralized at lower efficiencies. The clinical courses of the 205 patients enrolled in the study were found to be mostly mild to moderate; however, an unexpectedly high fraction (27%) of patients exhibited severe illness. One patient died from kidney failure and showed symptoms of generalized subcutaneous hemorrhage. The results provide molecular, serodiagnostic, and clinical evidence that DOBV-Aa is a common pathogen in East Europe that causes large outbreaks of HFRS.Hemorrhagic fever with renal syndrome (HFRS) is an infectious disease caused by hantaviruses in Asia and Europe (16,20) and most probably in Africa (13; our unpublished results). In the Americas, the autochthonous hantavirus species cause the hantavirus (cardio)pulmonary syndrome (24,26). Hantaviruses carry trisegmented negative-strand RNA genomes and belong to the family Bunyaviridae. Different rodent species are known to be the natural hosts of the currently identified hantaviruses pathogenic for humans (16,20). The viruses are transmitted to humans by aerosolized rodent excreta. Shrews were shown to be alternative hantavirus hosts (14, 31); however, the clinical significance of shrew-borne hantaviruses is still unclear.The demonstration of viral nucleotide sequences in specimens derived from patients with HFRS gives a clue to the involvement of a particular virus in the infection and allows its detailed molecular phylogenetic characterization. Because of the short-term viremia typical for human hantavirus infections, viral genetic material can best be amplified from blood or plasma during the first days after the onset of clinical symptoms (16). In contrast, serotyping of neutralizing antibodies is suggested to be most significant when convalescent-phase sera from the patients are used (19).HFRS cases in the European administrative regions of Russia are contributing to 97% of the total number of HFRS cases registered in Russia. Until recently, the majority of HFRS cases in European Russia were caused by Puumala virus (PUUV) and considerably fewer (mainly sporadic cases) were caused by Dobrava-Belgrade virus (DOBV) infections. However, during the period from 1991 to 2006, three l...

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ABSTRACT. European Russia is a highly endemic area of hemorrhagic fever with renal syndrome (HFRS), a rodent-borne zoonotic disease, caused by hantaviruses. In total, 145 small mammals of four species (Myodes glareolus, Apodemus flavicollis, A. agrarius, and A. uralensis) were trapped in the Samara region of European Russia in August 2005 and examined for the presence of hantavirus (HV). Anti-HV antibodies were found in six of 68 (8.8%) M. glareolus and in one of 19 (5.3%) A. flavicollis by indirect immunofluorescent antibody assay (IFA). The Puumala virus (PUUV), which is one of the hantavirus species, was detected in the lungs of seven M. glareolus by RT-PCR. The virus S-segment was extremely similar (96.2% to 99.3%) to the sequence found in a fatal case of HFRS in the Samara region. Phylogenetic analyses of S and M segments showed that the Samara PUUVs form a cluster within the Russian Volga lineage and apparently differ from other European PUUVs. Anti-PUUV antibodies were found in blood sera from seven HFRS patients and from one undiagnosed patient from the Samara region, using IFA and an enzyme-linked immunosorbent assay (ELISA). These data suggest that the bank vole M. glareolus is a primary natural reservoir and vector for PUUV, which is the main causative agent of HFRS in humans in the Samara region.KEY WORDS: epidemiology, hantavirus, hemorrhagic fever with renal syndrome, Puumala virus, rodents.J. Vet. Med. Sci. 71(12): 1569-1578, 2009 Hantaviruses belong to the genus Hantavirus, within the family Bunyaviridae, and cause two forms of human illness. These zoonoses include hemorrhagic fever with renal syndrome (HFRS), which occurs in Asia and Europe and is caused by the Hantaan virus (HTNV), Seoul virus (SEOV), Puumala virus (PUUV), Dobrava-Belgrade virus (DOBV), and Amur virus (AMRV). The second form of illness is hantavirus (cardio) pulmonary syndrome (HPS), which occurs in the Americas and is caused by the Sin Nombre virus, Andes virus, and other hantaviruses [13,28,33]. Hantaviruses are transmitted by aerosolized excreta from their natural hosts, mainly rodents of the family Muridae. Particular hantavirus species are usually harbored by a single rodent species, or by a few closely related rodent species, which indicates co-evolution and co-speciation of hantaviruses with their hosts. The virus genome contains three segments of negative-stranded RNA: the large (L) segment encodes a viral RNA-dependent RNA polymerase, the medium (M) segment encodes a glycoprotein precursor, and the small (S) segment encodes a nucleocapsid protein (NP) [34].In