Letter and Reply: Genetic interaction between Dobrava and Saaremaa hantaviruses: now or millions of years ago?

Abstract

In their paper (3), Klempa and coauthors reported results on (phylo)genetic analyses of hantaviruses occurring in two species of Apodemus mice, Dobrava virus (DOBV)-Af (from DOBV associated with A. flavicollis) and DOBV-Aa (associated with A. agrarius), and concluded that “DOBV-Af and DOBV-Aa are distinct but also subject to genetic exchanges that affect their evolutionary trajectories.” From these grounds, they then criticize our view that DOBV-Aa is a distinct hantavirus species, Saaremaa virus (SAAV) (1, 7, 9). (When we first discovered SAAV, it was designated a genetic lineage of DOBV [5, 8], and it was only with accumulating data that we came to the conclusion that it represents a distinct, new hantavirus.) We feel that the claim of Klempa et al. for currently occurring genetic exchanges between DOBV and SAAV is not well grounded and their view lacks an evolutionary dimension. Although DOBV and SAAV are closely related, there are three most important differences. (i) While DOBV causes severe hemorrhagic fever with renal syndrome (fatality up to 12%), SAAV causes a milder form of the disease, similar to nephropathia epidemica (references 2 and 4 and our unpublished data). (ii) DOBV and SAAV are clearly differentiated by classical serology (reference 1 and our unpublished data). (iii) DOBV is lethal to suckling mice, while SAAV is not (J. Klingstrom and A. Lundkvist, unpublished data). In fact, in answering the crucial question of whether DOBV and SAAV are distinct entities or not, Klempa et al. came up with some controversy themselves: on the one hand, the two types are distinct; on the other, they are subject to genetic interactions (reassortment and recombination). Following this logic, DOBV and SAAV should, at the same time, be reproductively isolated and capable of “breeding”. In our opinion, we are dealing here with a case of host switching, which occurred in the evolution of these hantaviruses (7, 9, 11), and we most recently obtained the crucial piece of evidence to support our view (6). Phylogenetic analysis revealed a discrepancy in the relationships of DOBV, SAAV, and Hantaan virus and their respective rodent hosts. This discrepancy is consistent with the transmission of (pre)DOBV/SAAV between A. flavicollis and A. agrarius, which resulted in the ecological and reproductive isolation of the two hantaviruses. Crucially, the time point of the host switching, 2.7 to 4.0 million years ago, was closer to the present than the estimated time of split between the two Apodemus species (<6.5 million years ago).