Widespread use of reverse transcription polymerase chain reaction has led to the realization that a multitude of rodent species harbor genetically distinct or related hantaviruses. Thus, a rapid method of predicting the pathogenic potential of newfound hantaviruses would assist in outbreak investigations. We examined the utility of analyzing and comparing phylogenetic trees based on the entire S-segment coding region of hantaviruses and those based on cytochrome B gene mitochondrial DNA sequences of rodents to ascertain the pathogenic potential of recently described arvicolid rodent-borne hantaviruses. Strains Tobetsu and Kamiiso from Clethrionomys rufocanus in Japan shared a common ancestry with Puumala virus strains from Clethrionomys glareolus (Figure 3), suggesting that hantaviruses harbored by grey-sided voles may similarly be pathogenic for humans. Phylogenetic analysis of mitochondrial DNA also revealed that Eothenomys regulus, the arvicolid-rodent reservoir of Muju virus, in sharing an ancestral node with Clethrionomys glareolus, might similarly harbor a pathogenic hantavirus. By extension, Eothenomys smithii and Eothenomys andersoni in Japan may also serve as reservoirs of pathogenic hantaviruses (Figure 4). By contrast, recently identified strains Lodz and Cacak from Microtus arvalis in Poland and from Pitymys subterraneus in Serbia, respectively, may not be pathogenic since they cluster with other Tula virus strains. Moreover, Microtus arvalis and Pitymys subterraneus are phylogenetically related to Microtus pennsylvanicus and Microtus californicus in the United States; their respective hantaviruses, Prospect Hill virus and Isla Vista virus, have not been implicated in human disease. In this regard as well, Khabarovsk virus from Microtus fortis in Russia may be nonpathogenic for humans. This pilot study shows the potential utility of employing mitochondrial DNA analysis of rodents to predict the pathogenicity of hantaviruses, as well as to determine which rodent species are likely to harbor hantaviruses.

Figure 3. Phylogenetic tree based on full-length Figure 4. Phylogenetic tree based on

S-genomic segment sequences of hantaviruses. mitochondrial DNA sequences of arvicolid

PUU (Puumala); TUL (Tula); KBR (Khabarovsk); rodents. Bootstrap values for 1,000 iterations

IV (Isla Vista); PH (Prospect Hill) and Muju. are shown in italics.