Experimental Cowpox Virus (CPXV) Infections of Bank Voles: Exceptional Clinical Resistance and Variable Reservoir Competence

Abstract

Cowpox virus (CPXV) is a zoonotic virus and endemic in wild rodent populations in Eurasia. Serological surveys in Europe have reported high prevalence in different vole and mouse species. Here, we report on experimental CPXV infections of bank voles (Myodes glareolus) from different evolutionary lineages with a spectrum of CPXV strains. All bank voles, independently of lineage, sex and age, were resistant to clinical signs following CPXV inoculation, and no virus shedding was detected in nasal or buccal swabs. In-contact control animals became only rarely infected. However, depending on the CPXV strain used, inoculated animals seroconverted and viral DNA could be detected preferentially in the upper respiratory tract. The highest antibody titers and virus DNA loads in the lungs were detected after inoculation with two strains from Britain and Finland. We conclude from our experiments that the role of bank voles as an efficient and exclusive CPXV reservoir seems questionable, and that CPXV may be maintained in most regions by other hosts, including other vole species. Further investigations are needed to identify factors that allow and modulate CPXV maintenance in bank voles and other potential reservoirs, which may also influence spill-over infections to accidental hosts.

In Vivo Characterization of a Bank Vole-Derived Cowpox Virus Isolate in Natural Hosts and the Rat Model

“…The outcome of all these animal experiments further substantiates the recent hypothesis of reservoir species-specific phylogenetic lineages within the CPXV classification [31]. As depicted in Table 4, different CPXV strains display clearly different behavior in the different corresponding presumed reservoir animals and the Wistar rat animal model.…”

“…Nevertheless, growth kinetics of CPXV GerMygEK 938/17 on Vero76 cells in comparison to those of other CPXV strains like Brighton Red, RatPox09, or the very closely related CPXV strain Ger2010MKY allowed no proposition concerning the in vivo virulence. While all four tested CPXV strains showed a very similar outcome in the replication kinetics on Vero76 cells, the results of the animal experiments differed markedly [31]. Along with a previous study, we concluded that in vitro assays could not predict in vivo properties or virulence differences [39].…”

“…However, the role and importance of bank voles as reservoir hosts for CPXV is still a matter of debate. Our recent studies from 2017 have justified doubts on the susceptibility of bank voles as reservoirs for CPXV, because independent of the CPXV-isolate or infection route used, virus shedding was never detectable and only very few bank voles showed antibody titers above 1:80 [31]. However, a bank vole-derived isolate for experimental inoculation was not available at this time.…”

“…As depicted in Table 4, different CPXV strains display clearly different behavior in the different corresponding presumed reservoir animals and the Wistar rat animal model. While a common vole-derived CPXV isolate (CPXV-like 2 clade) leads to respiratory signs and prominent virus shedding in both the original reservoir animal and an animal model (Wistar rats) for an accidental host [27], the inoculated bank voles revealed no clinics, no virus shedding and a low titer seroconversion rate of 60% [31]. Vice versa, common voles inoculated with the bank vole-derived CPXV isolate (CPXV-like 3 clade) exhibited neither virus shedding nor seroconversion.…”

“…They exhibited even more prominent respiratory clinical signs than common voles [27]. In addition, experimental studies with the other putative reservoir host, the bank vole, were performed [31]. However, independent of the application route or the CPXV isolate used (different phylogenetic clades and host origin) or the bank vole evolutionary lineage, viral shedding was not detectable.…”