Puumala and Dobrava viruses cause hemorrhagic fever with renal syndrome in Bosnia-Herzegovina: Evidence of highly cross-neutralizing antibody responses in early patient sera

Abstract

Hantavirus infection was diagnosed serologically by mu-capture IgM and IgG ELISAs in hemorrhagic fever with renal syndrome (HFRS) patients admitted to Tuzla Hospital, Bosnia-Herzegovina. The results indicated that more than one hantavirus caused the outbreak. To address the question of which hantavirus serotypes were involved, sequentially drawn sera were analyzed by focus reduction neutralization test (FRNT) for antibodies against Puumala, Hantaan, Dobrava, and Seoul hantaviruses. The data revealed that acute- or early convalescent-phase sera, even when drawn as late as 3 weeks after the onset of disease, could not be used for typing of the causative hantavirus; a significant number of these samples showed similar reactivity of neutralizing antibodies to several different hantavirus serotypes. Moreover, although several acute-phase sera showed the highest FRNT titer to Hantaan virus, convalescent sera from these patients in all cases showed high specificity for Puumala or Dobrava viruses. This phenomenon, interpreted as a cross-neutralizing primary antibody response, makes several earlier reports concerning causative agents of HFRS questionable. Serological examination of small rodents trapped in the endemic area identified Puumala- and Dobrava-like virus infections. RT-PCR and sequencing of rodent lung samples identified Dobrava virus in one yellow-necked field mouse (Apodemus flavicollis). Cross-FRNT data, using polyclonal rabbit antibodies, clearly confirmed Dobrava virus as a unique hantavirus serotype. In conclusion, the results revealed that both Puumala- and Dobrava-like viruses caused HFRS in Bosnia-Herzegovina, whereas no signs of Hantaan or Seoul virus involvement were found.

High prevalence of Seoul hantavirus in a breeding colony of pet rats

“…An 80% reduction of the number of foci, as compared with the virus control, was used as a criterion for virus neutralisation titres and the titrations were performed as described earlier [30] (online Supplementary Material). Serum samples collected in January 2013 from two HFRS patients (Cherwell and Wrexham) were also tested using specific hantavirus FRNTs against SEOV, DOBV, PUUV and HTNV.…”

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

“…2 An association of DOB virus with HFRS was recently found in patients from southeastern Europe (Albania, Greece, former Yugoslavia) and Russia. [5][6][7] In a study performed in Estonia (northeastern Europe), Plyusnin and others 8 demonstrated the presence of DOB virus in A. agrarius, the natural host of HTN virus in Asia. 1,2 In Slovakia (central Europe), HFRS is a well-known disease; clinical cases as well as infected rodents have been serologically diagnosed using HTN or PUU virus antigens.…”

Serologic Investigation of Hantavirus Infection in Patients with Previous Thrombocytopenia, and Elevated Urea and Creatinine Levels in an Epidemic Region of Turkey

“…The focus reduction neutralization tests (FRNT) were performed on seropositive samples at the Swedish Institute for Communicable Dis- (12), and DOBV Slovenia strain (13) were used for FRNT analyses. The tests were performed as previously described by Lundkvist et al (14). In this protocol, the ELISA and/or immunoblotting seropositive samples were serially diluted and mixed with an equal volume of diluted virus, containing 30-70 focus forming units/100 ml.…”