To examine the host association of Tula virus (TULV), a hantavirus present in large parts of Europe, we investigated a total of 791 rodents representing 469 Microtus arvalis and 322 Microtus agrestis animals from northeast, northwest, and southeast Germany, including geographical regions with sympatric occurrence of both vole species, for the presence of TULV infections. Based on serological investigation, reverse transcriptase PCR, and subsequent sequence analysis of partial small (S) and medium (M) segments, we herein show that TULV is carried not only by its commonly known host M. arvalis but also frequently by M. agrestis in different regions of Germany for a prolonged time period. At one trapping site, TULV was exclusively detected in M. agrestis, suggesting an isolated transmission cycle in this rodent reservoir separate from spillover infections of TULV-carrying M. arvalis. Phylogenetic analysis of the S and M segment sequences demonstrated geographical clustering of the TULV sequences irrespective of the host, M. arvalis or M. agrestis. The novel TULV lineages from northeast, northwest, and southeast Germany described here are clearly separated from each other and from other German, European, or Asian lineages, suggesting their stable geographical localization and fast sequence evolution. In conclusion, these results demonstrate that TULV represents a promiscuous hantavirus with a large panel of susceptible hosts. In addition, this may suggest an alternative evolution mode, other than a strict coevolution, for this virus in its Microtus hosts, which should be proven in further large-scale investigations on sympatric Microtus hosts.Hantaviruses (genus Hantavirus, family Bunyaviridae) are characterized by a tripartite RNA genome of negative polarity. The small (S) genome segment of about 1.7 kb encodes the nucleocapsid (N) protein that is associated as a multimer with the viral RNA genome. The medium (M) segment of about 3.6 kb encodes a glycoprotein precursor that is cotranslationally cleaved at a highly conserved WAASA motif into the G1 and G2 envelope glycoproteins. These proteins form oligomers which mediate the interaction of the virus with the cellular receptor. The large (L) segment of about 6.5 kb encodes the RNA-dependent RNA polymerase that functions as transcriptase and replicase (for a review, see reference 57).In general, hantaviruses are harbored by persistently infected rodent reservoir hosts which shed the hantaviruses by urine, feces, and saliva. Therefore, the major route of transmission to humans is by inhalation of aerosols originating from virus-contaminated urine or feces (for a review, see reference 58). The high stability of hantaviruses in nature allows indirect transmission and underlines the importance of environmental factors on the frequency of transmission (31). An alternative route of virus transmission to humans is by rodent bites (10). Human-to-human transmission has exclusively been observed for the South American Andes virus (42).The congruent phylogenetic affinities of h...

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Background: The objective of the study was to develop and evaluate IgM and IgG ELISAs and an IgG Western blot test for the serological detection of human infections with Andes virus (ANDV), the major cause of hantavirus cardiopulmonary syndrome (HCPS) in South America. Methods: The entire nucleocapsid (N) protein-encoding sequence of ANDV (strain AH-1) was cloned and expressed in the yeast Saccharomyces cerevisiae. The polyhistidine-tagged recombinant N (rN) protein of ANDV was purified by nickel-chelation chromatography and characterized by its reactivity with different N-specific monoclonal antibodies. To detect an antibody response directed against ANDV in humans, indirect IgM and IgG ELISAs and an IgG Western blot test based on ANDV rN antigen were developed. The evaluation of the tests was performed using a negative serum panel and 63 blinded sera from Argentina and Chile, containing acute-phase and convalescent sera from HCPS patients. Results: The specificities and sensitivities for the IgM and IgG ELISAs were demonstrated to be very high. The IgG ELISA data were confirmed by the IgG Western blot assay based on the same rN antigen. Almost all anti-ANDV-positive sera reacted to higher endpoint titers with N protein of ANDV than with those of Sin Nombre, Laguna Negra or Puumala virus. The cross-reactivity of anti-ANDV-N IgG-positive sera to rN proteins of other hantaviruses was found to be increased with time after the onset of HCPS. Conclusion: The high sensitivity of the novel assays should facilitate early diagnosis of ANDV infections and might contribute to a successful treatment of HCPS patients.