Host-pathogen dynamics of squirrelpox virus infection in red squirrels (Sciurus vulgaris)

•We investigate the time course of infection of squirrelpox virus in red squirrels.•Most animals will succumb to this normally lethal infection in about 3 weeks.•Virus replication is primarily in the skin and oral mucosa, not in internal organs.•The greatest amounts of viral DNA are found in skin lesions and also in the saliva.•Environmental deposition of the virus is a likely factor in its transmission.

To improve our understanding of squirrelpox virus (SQPV) infection in the susceptible host, three red squirrels were challenged with wild-type SQPV via scarification of the hind-limb skin. All squirrels seroconverted to the infection by the end of the experiment (17 days post-challenge). Challenged animals suffered disease characterised by the development of multiple skin and oral lesions with rapid progression of skin lesions at the infection site by day 10 post-challenge. No internal pathological changes were found at post-mortem examination. A novel SQPV Taqman® Real-time PCR detected viral DNA from multiple organs, with the largest amounts consistently associated with the primary and secondary skin and oral lesions where viral replication was most likely occurring. Immunohistochemistry clearly detected viral antigen in the stratified squamous epithelium of the epidermis, tongue and the oropharyngeal mucosa-associated lymphoid tissue and was consistently associated with histological changes resulting from viral replication. The lack of internal pathological changes and the detection of relatively low levels of viral DNA when compared with primary and secondary skin lesions argue against systemic disease, although systemic spread of the virus cannot be ruled out. This study allowed a comprehensive investigation of the clinical manifestation and progression of SQPV infection with a quantitative and qualitative analysis of virus dissemination and shedding. These findings suggest two separate routes of SQPV transmission under natural conditions, with both skin and saliva playing key roles in infected red squirrels.