Primary mouse dermal fibroblast cell cultures as an in vitro model system for the differential pathogenicity of cross-species herpesvirus papio 2 infections.

Infection of mice with herpesvirus papio 2 (HVP2) parallels zoonotic monkey B virus infections. A major benefit of the HVP2/mouse model is the existence of two HVP2 subtypes: HVP2nv rapidly invades and destroys the CNS while HVP2ap produces no clinical signs and mild histopathological lesions. However, in the natural baboon host, no difference in pathogenicity of HVP2 subtypes is evident. Primary dermal fibroblast cells were evaluated as a model system for defining virus-host interactions that influence the outcome of a cross-species infection. No differences in plaque formation or virus replication were observed between HVP2 subtypes in primary baboon dermal fibroblast cultures. In contrast, when primary mouse dermal fibroblasts (PMDF) were infected, HVP2nv replicated to higher titers and was more efficient at shutting down host-cell protein synthesis compared to HVP2ap. HVP2ap-infected PMDF cells produced more IFN-beta compared to HVP2nv, and IFN-beta pretreatment of PMDF cultures inhibited HVP2ap replication but did not affect HVP2nv. The differential pathogenicity of HVP2 subtypes in mice and the lack of such differences in the natural baboon host are recapitulated in the primary dermal fibroblast cell culture system. This model may prove useful in examining early, local, host responses that influence the outcome of cross-species infections.