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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.

The work is devoted to clarify the etiological aspects of the hemorrhagic fever with renal syndrome (HFRS), clinical and epidemiological features that are closely linked to the etiology, as well as to development of methods and products for specific diagnosis and vaccine prevention of hantavirus infection. That regard to hantaviruses a set of virological, immunological and molecular-genetics methods were developed significantly enhance the effectiveness of the specific diagnostics of HFRS. The features of humoral immunity in HFRS were identified and atypical clinical forms of HFRS was istablished; indicators of natural immunity to hantavirus in the population living in different regions of Russia and the former Soviet republics have been identified that allowed us to refine nosological area of HFRS; new, previously unknown natural foci of HFRS, including hantavirus RNA, in the central regions of Russia and in the subtropical zone of Krasnodar region have been identified and studied; 76 strains and 70 isolates of 9 rodent species and one species of birds, as well as from the blood of patients with HFRS and sectional materials from HFRS dead patients have been isolated and identified; new hantavirus species - Khabarovsk, Taimyr-Topografov, Adler, as well as two new genotypes Dobrava/Belgrad virus - Kurkino and Sochi have been identified; species composition of small mammals - the natural reservoir of hantaviruses was the refined; etiological role and epidemiological importance of different hantaviruse types in HFRS incidence structure was established; the existence of new etiologically distinct hantavirus infections with significant epidemiological differences has been proven; manufacturing techniques and methods of control of the culture inactivated vaccine against HFRS has been developed.

The frequency of chromosome damage was studied in the carriers of virus of the hemorrhagic fever with renal syndrome (Puumala virus) and in noninfected animals from two laboratory colonies and two natural populations of bank vole. In the laboratory colony, where Puumala virus persisted for three years, multiaberrant (“rogue”) cells were found in the bone marrow; the mean frequencies of both structural and numeral chromosome abnormalities were significantly enhanced. In the other laboratory colony, no Puumala virus was detected during all 30 years of its existence, but the mean frequencies of structural chromosome damage were increased to the same degree probably due to the prolonged breeding under laboratory conditions, which resulted in suppression of immunity and DNA repair. The voles from the natural populations were more resistant to the clastogenic viral effect, but they also had multiaberrant cells which served as indicators of viral infection. The data obtained support the hypothesis that viral infections increase mutation rate, contributing thereby to the evolution process.

Specific features of hantavirus infection in bank vole (Clethrionomys glareolus) were studied in the endemic area of hemorrhagic fever with renal syndrome (HFRS) in the foothills of the Ural mountains, using long-term observations on living animals by the capture-mark-recapture (CMR) method. The results demonstrated that the infection naturally circulating in the voles is chronic (lasting for up to 15 months) and asymptomatic, with a peak of Puumala virus accumulation and release from the organism during the first month after infection. It was shown that the bank vole population includes young animals with maternal immunity, which remain resistant to the Puumala virus infection for 3-3.5 months. The infection rate in voles depended on the age and sexual maturity of animals. The greatest proportion of seropositive animals was observed among overwintered males. Seroconversion in voles was more frequent during the period of high reproductive activity.

An immunoglobulin G avidity assay was used to determine recent and past hantavirus infection in bank voles (Clethrionomys glareolus). Sera of experimentally infected bank voles were studied at different time intervals. The avidity of specific IgG increased over time after infection. This experimental data were used to estimate the time after onset of hantavirus infection in naturally infected bank voles caught in an endemic area. The possibility to discriminate between recently infected animals and animals infected some time ago is important since the proportion of recently infected bank voles represents the intensity of the epizootic which in turn correlates to the risk of humans to contract the disease.

Inapparent, persisting hantavirus infection was demonstrated in bank voles (Clethrionomys glareolus) after experimental infection with strain Kazan 6 C.g. isolated in the U.S.S.R. Virus, viral antigen, antibodies, and the capacity for horizontal transmission of infection were demonstrable throughout the period of observation (13 months), the highest titers being observed 10–20 days postinfection. Direct correlation was detected between the intensity of horizontal transmission and the level of humoral immunity. The progeny of infected females were shown to be passively immune for 30–45 days after birth and to be relatively resistant to infection with strain Kazan 6 C.g. during that period.

Four strains of haemorrhagic fever with renal syndrome virus (HFRSV) from rodents or patients in European U.S.S.R. foci of HFRS were isolated in laboratory bred C. glareolus. The sensitivity of these animals to HFRSV was compared with that of five other laboratory and wild animals.

The use of indirect fluorescent antibody testing (IFAT) and enzyme linked immunosorbant assay (ELISA) procedures allowed the hemorrhagic fever with renal syndrome (HFRS) virus antigen to be detected not only in the known reservoir host, Clethrionomys glareolus, but also in 7 other species of small mammals in European foci of the U.S.S.R. Marked viscerotropism of HFRS virus and the participation of brown fat in maintaining the infection in rodents were demonstrated. The frequency of detection of circulating antigen and antibody to HFRS virus in rodents is indicative of the high level of activity of the virus in its epizootic foci.