molecular evolution and pathogenic relevance
Hantaviruses (Bunyaviridae family) are rodent-borne bunyaviruses that cause hemorrhagic fever with renal syndrome (HFRS) in Eurasia. This thesis presents novel data about two European hantaviruses, Dobrava virus (DOBV) and Tula virus (TULV). DOBV is an important etiologic agent of HFRS in Europe. DOBV strains were found to be hosted by at least two different rodent species, yellow-necked mouse (Apodemus flavicollis) and striped field mouse (A. agrarius). According to their natural hosts they form the distinct genetic lineages DOBV-Af and DOBV-Aa, respectively. We have determined and analysed the complete S and M, and partial L segment nucleotide sequences of sympatrically occurring DOBV-Af and DOBV-Aa strains from Central Europe. Molecular phylogenetic analyses gave evidence for genetic reassortment in the evolution of the virus species. Moreover, we amplified a DOBV-Aa nucleotide sequence from a DOBV-seropositive HFRS patient from Germany. This is the first molecular identification of human infection by DOBV in Central Europe and the first direct proof that a virus strain related to the DOBV-Aa lineage, carried by A. agrarius rodents, is able to cause HFRS. Under biosafety level 3 conditions, we have established a DOBV isolate named Slovakia (SK/Aa) from an A. agrarius animal captured in Slovakia. SK/Aa, as the only isolate clearly belonging to the DOBV-Aa lineage, can be taken as the representative of this virus lineage. The new virus isolate, in comparison to a DOBV-Af strain, was used for serotyping neutralising antibodies of HFRS patients in Central Europe by the use of a focus reduction neutralisation assay. Most patients'' sera exhibited a higher end-point titer towards SK/Aa suggesting that DOBV-Aa strains are responsible for most of the DOBV HFRS cases in this region. TULV is carried by European common voles (Microtus sp.). Its pathogenic potential for humans was rather unknown. We have described the first case of HFRS which can be associated with TULV infection. Moreover, TULV strains detected in M. arvalis near the home village of the patient in North-East Germany clustered with strains from Poland and represent a new, well-supported genetic lineage within the TULV species. In addition to DOBV and longer known Puumala virus, TULV is most likely an additional causative agent of HFRS in Central Europe.
School:Humboldt-Universität zu Berlin
Source Type:Master's Thesis
hemorrhagic fever with renal syndrome (HFRS)
Date of Publication:02/09/2005