[Show abstract][Hide abstract] ABSTRACT: Sochi virus was recently identified as a new hantavirus genotype carried by the Black Sea field mouse, Apodemus ponticus. We evaluated 62 patients in Russia with Sochi virus infection. Most clinical cases were severe, and the case-fatality rate was as high as 14.5%.
[Show abstract][Hide abstract] ABSTRACT: For the period from 2001 to 2011 zoological and epizootological studies in more than 100 points of Northwestern Caucasus including territories of Krasnodar Region and Republic of Adygea were carried out. 8723 specimens of small mammals represented by 20 rodent species and 7 insectivorous species were captured and examined. Organs and blood from 5057 specimens of creatures were studied for hantavirus infection. The presence of natural foci of circulation of 2 species of hantavirus--Dobrava/Belgrade and Tula--was established. Sochi viruses and presumably Kurkin with main natural hosts--Caucasian wood and field mice belong to the first species. Tula and Adler viruses with the main host--Microtus genus vole belong to the second species. Quantitative characteristics of infection of small mammals of various species during different seasons and years on the examined territories were obtained, that allowed to create a map of allocation of foci of hantavirus circulation that differ by structure.
Zhurnal mikrobiologii, epidemiologii, i immunobiologii 03/2014;
[Show abstract][Hide abstract] ABSTRACT: A new genotype of Dobrava-Belgrade virus (DOBV), Sochi virus, was found in the Black Sea field mouse, Apodemus ponticus. This mouse is naturally occurring in the Southern European Russia and transcaucasian countries between the Black and the Caspian Sea. Recently, cell culture isolates of Sochi virus have been generated from A. ponticus and an HFRS patient with fatal outcome.
At the present state of knowledge, Sochi virus seems to be the most dangerous representative of DOBV. Virus diagnostics in patients was accomplished by immunofluorescence assay, serotyping of neutralizing antibodies, and RT-PCR amplification of viral genome segments. In phylogenetic analyses we found a spatial clustering of the viral nucleotide sequences derived from patients and mice trapped at different localities of the Russian Black Sea coast region demonstrating Sochi virus as the causal pathogenic agent in humans.
We currently oversee in detail the clinical courses of 51 patients with confirmed Sochi virus infection. The case fatality rate was determined to be as high as 14%. Nearly 60% of clinical courses were defined as severe (including deaths) and nearly 40% as moderate. Four times more males than females were affected. Quite unusual for hantavirus disease, also young people became ill due to Sochi virus infection; 10% of patients were found between 7 and 15 years old and the age average of all patients was not much higher than 30 years.
There is an urgent need to monitor the epidemiology of the new virus—not only because of its health-threatening character in this particular geographical area but also because of its potential ability to overcome host species barriers. Colonization of nearly related host species, as A. flavicollis or A. sylvaticus, by the virus could dramatically increase its geographical spread and consequently further enhance the danger for the human population.
[Show abstract][Hide abstract] ABSTRACT: From 2000 to 2011 85 600 cases of hemorrhagic fever with renal syndrome (HFRS) were registered in Russian Federation. Epidemically active foci of HFRS infection are located generally in temperate latitudes of the European part and the Far East. In the Far East regions whose fraction of all the HFRS disease cases in Russia is around 2%, the causative agents of the infection are Hantaan, Amur, Seoul hantaviruses, the natural reservoir for those are striped field mouse, Korean field mouse and brown rat. In the European part of Russia the causative agent of the infection are Puumala hantavirus as well as 2 genetic subtypes of Dobrava virus, the main reservoirs of those in the nature are bank vole, striped field mouse and Black Sea field mouse, respectively. 9 strain of Puumala and 10 strains of Dobrava virus were isolated. Based on sequencing of Dobrava virus strains significant differences were detected between Dobrava virus strains isolated from Black Sea field mouse from Sochi and striped field mouse from Lipetsk Region. Cultural inactivated vaccine against HFRS was developed and completed preclinical trials.
Zhurnal mikrobiologii, epidemiologii, i immunobiologii 06/2013;
[Show abstract][Hide abstract] ABSTRACT: The monoclonal antibodies to Puumala, Dobrava, Hantaan, and Seoul hantaviruses were obtained using mice. The viruses were known to cause HFRS, and two variants of ELISA were designed. First, Hanta-PUU variant, was constructed using monoclonal antibodies to Puumala virus envelope glycoprotein (G(N):G(C)) for detecting only Puumala virus antigen. The second, Hanta-N variant, was constructed using monoclonal antibodies to Dobrava and Puumala nucleocapsid proteins for detecting four above mentioned hantaviruses. Both Hanta-PUU and Hanta-N assays were reliable in detecting specific hantavirus antigens and the immunogenecity of hantavirus vaccines.
[Show abstract][Hide abstract] ABSTRACT: 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.
Archives of Virology 10/2012; 158(3). DOI:10.1007/s00705-012-1514-5 · 2.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Antigenic diversity among different hantaviruses requires a variety of reagents for diagnosis of hantavirus infection. To develop a diagnostic method applicable to various hantavirus infections with a single set of reagents, we developed an enzyme-linked immunosorbent assay (ELISA) using recombinant nucleocapsid proteins of three hantaviruses, Amur, Hokkaido, and Sin Nombre viruses. This novel cocktail antigen-based ELISA enabled detection of antibodies against Hantaan, Seoul, Amur, Puumala, and Sin Nombre viruses in immunized laboratory animals. In wild rodent species, including Apodemus, Rattus, and Myodes, our ELISA detected antibodies against hantaviruses with high sensitivity and specificity. These data suggest that our novel diagnostic ELISA is a useful tool for screening hantavirus infections and could be effectively utilized for serological surveillance and quarantine purposes.
Journal of Veterinary Medical Science 05/2012; 74(9):1237-42. DOI:10.1292/jvms.12-0006 · 0.78 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Sochi virus, a novel genetic variant of Dobrava-Belgrade virus, was isolated in cell culture from a fulminant lethal case of hantavirus disease presenting with shock and combined kidney and lung failure. Sochi virus is transmitted to humans from host reservoir Apodemus ponticus and must be considered a life-threatening emerging agent.
[Show abstract][Hide abstract] ABSTRACT: The findings suggest that there are natural foci of hantavirus infection in the Tambov Region. There is evidence that Dobrava/Belgrade hantavirus (DOB-Aa) was a leading etiological agent in the outbreak of the disease in the winter of 2006-2007. Epidemiological analysis showed that the outbreak of hemorrhagic fever with renal syndrome (HFRS) afflicted the region during November to April, by reaching its peak in January (52.2%). Among the patients with HFRS, rural dwellers were 91%. People were infected with the virus mainly by taking care of domestic animals (97.2%). The reservoir of the virus and the source of its human infection in the outbreak was a field mouse, its western subspecies Apodemus agrarius agrarius, which was absolutely dominated among all the virus carriers.
[Show abstract][Hide abstract] ABSTRACT: Puumala virus (PUUV) and other Arvicolinae-borne hantaviruses are difficult to cultivate in cell culture. To isolate these hantaviruses efficiently, hantavirus nucleocapsid protein (NP)-positive but seronegative wild rodents were selected by NP-detection ELISA. Three of 68 Myodes glareolus captured in Samara, Russia, were NP-positive and seronegative. Syrian hamsters were inoculated with lung homogenates from NP-positive rodents for virus propagation. Virus isolation in vitro was carried out by inoculation of lung homogenates of NP-positive hamsters to Vero E6 cell monolayers. Two PUUV strains (Samara49/CG/2005 and Samara94/CG/2005) from M. glareolus were isolated in Vero E6 cells. Nucleotide and amino acid sequence identities of the S segment of these isolates to those of PUUV F-s808 from a fatal HFRS patient in Samara region were 96.7-99.3% and 99.3-100.0%, respectively. Morphologic features of Vero E6 cells infected with PUUV strain Samara49/CG/2005 were quite similar to those of Hantaan virus-infected cells. Isolation of Hokkaido virus from Myodes rufocanus captured in Hokkaido, Japan, was also performed. Hokkaido virus NP and RNA were recovered and maintained in hamsters. These results suggest that inoculation of Syrian hamsters with rodent samples is an efficient method for the isolation and maintenance of PUUV and other Arvicolinae-borne hantaviruses.
[Show abstract][Hide abstract] 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.
Journal of Veterinary Medical Science 12/2009; 71(12):1569-78. DOI:10.1292/jvms.001569 · 0.78 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: Puumala virus (PUUV), a causative agent of hemorrhagic fever with renal syndrome (HFRS), is prevalent in Europe and European Russia. No vaccine has been developed for PUUV-associated HFRS, primarily because of the low viral yield in cultured cells. A PUUV strain known as DTK/Ufa-97 was isolated in Russia and adapted for growth in Vero E6 cells maintained in serum-free medium. The DTK/Ufa-97 strain produced a higher viral titer in serum-free medium, suggesting that it may prove useful in the development of an HFRS vaccine. When PUUV-infected Vero E6 cells were grown in serum-free medium, the DTK/Ufa-97 strain yielded more copies of intracellular viral RNA and a higher viral titer in the culture fluid than did the Sotkamo strain. Phylogenetic analysis revealed that PUUVs can be classified into multiple lineages according to geographical origin, and that the DTK/Ufa-97 strain is a member of the Bashkiria-Saratov lineage. The deduced amino acid sequences of the small, medium, and large segments of the DTK/Ufa-97 strain were 99.2% to 100%, 99.3% to 99.8%, and 99.8% identical, respectively, to those of the Bashkirian PUUV strains and 96.9%, 92.6%, and 97.4% identical, respectively, to those of the Sotkamo strain, indicating that the PUUVs are genetically diverse. However, DTK/Ufa-97 and other strains of PUUV exhibited similar patterns of binding to a panel of monoclonal antibodies against Hantaan virus. In addition, diluted antisera (i.e., ranging from 1:160 to 1:640) specific to three strains of PUUV neutralized both homologous and heterologous viruses. These results suggest that the DTK/Ufa-97 strain is capable of extensive growth and is antigenically similar to genetically distant strains of PUUV.
The Japanese journal of veterinary research 12/2008; 56(3):151-65. · 0.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Dobrava-Belgrade virus (DOBV) is a European hantavirus 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.
[Show abstract][Hide abstract] ABSTRACT: 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 common (Microtus arvalis) (Tula virus) voles. These species were frequently found to have their untypical hantaviruses, which was most commonly observed in small wood mice. It is suggested that the small wood mouse is likely to take a certain part in maintaining the circulation of Dobrava-Belgrad virus.
[Show abstract][Hide abstract] ABSTRACT: The authors of the article describe two cases of hemorrhagic fever with renal syndrome (HFRS) with prevalence of signs of nervous system involvement. The first case was a 40-year-old woman with moderate HFRS, who developed Guillain-Barre syndrome of axonal-demyelinating polyneuropathy. An important observation was the absence of hemorrhagic or renal syndrome; combined therapy including plasmapheresis was successful. The second case demonstrated polymorphism of HFRS clinical manifestations with prevalence of neurological symptoms, which consisted in encephalopathy and no renal failure signs; hemorrhagic syndrome was moderate. In both cases the diagnosis was confirmed by elevated titer of antibodies to HFRS virus, belonging to the group of hantaviruses.
[Show abstract][Hide abstract] ABSTRACT: 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 hantaviruses has provided evidence that 13 viral RNA isolates from the A. (S.) ciscaucasicus belong to the Dobrava/Belgrade virus clade; however the RNA isolate from the Microtus majori belong to the Tula virus clade.
[Show abstract][Hide abstract] ABSTRACT: Hemorrhagic fever with renal syndrome (HVRS) has been for decades a topical problem for healthcare systems of many countries in the Eurasian continent. Viruses triggering HVRS alongside with other related viruses (but not pathogenic to man) were discovered in 70-80-ies and formed a new genus Hantavirus of the Bunyaviridae family. The study results of a severe outbreak of the respiratory disease with the mortality rate of 60% (South-West of the USA, 1933) showed that hantaviruses were also among the causative agents. Later, the disease was designated as hantavirus cardio-pulmonary syndrome. By now, it has been established that hantaviruses are wide spread with different rodents being their carriers. The discussed viruses cause, in rodents, a chronic asymptomatic infection and are transferred, later, to man by the aerogenic path through excretions of infected animals. Studies of hantaviruses have been restricted for a long time due to their high pathogenicity (protection equipment not below than the P-3 level is needed), because of a lack of a laboratory model of infected animals and because of a low growth in cell cultures. With the rapid development and application of molecular biological techniques of the recent years, substantial progress has been made in studies of hantaviruses. Different aspects of hantavirus ecology, molecular biology, morphology, pathogenesis and diagnostics are discussed in the offered survey.