Host-pathogen interactions in human polyomavirus 7 (HPyV7)-associated skin disease

The recently discovered polyomavirus HPyV7 is emerging as a cause for intensely itchy skin eruptions in immunocompromised hosts. We performed an in-depth investigation of a renal transplant recipient with HPyV7-associated eruption that resolved with reduction of immunosuppression and treatment with acitretin. RNA sequencing of diseased skin revealed a strong interferon response that decreased upon clinical resolution, correlating with cessation of viral protein expression and seroconversion for HPyV7-specific antibodies. Sequencing of HPyV7 revealed a mutagenic hotspot within a previously undetected agnoprotein gene. The cytosine deaminases APOBEC3A and APOBEC3B were significantly upregulated in affected skin, and the observed viral sequence modifications were consistent with APOBEC activity, suggesting that it may play a role in viral evolution in diseased skin. Through this multi-omic approach, we confirm a pathogenic role for HPyV7, identify signature components of the host response, and highlight the complex interplay between the skin immune microenvironment and viral mutagenesis. 3 skin biopsy RNA-seq samples were analyzed: less affected skin biopsy (3 replicates: 2 technical replicates first and a 3rd replicate done during the late-treatment run), more affected skin biopsy (3 replicates: 2 technical replicates first and a 3rd replicate done during the late-treatment run), late-treatment skin biopsy (1 sample).