1031 Human polyomavirus 7 (HPyV7)-associated eruptions in immunocompromised hosts

Since its discovery in normal skin, 5 cases of HPyV7-associated rashes have been reported. We present the clinical, viral, and immunologic findings from a renal transplant recipient with a pruritic, pink-grey, scaly eruption. Histopathology demonstrated the “peacock plumage” pattern characteristic of HPyV6/7-associated rashes and HPyV7 viral DNA was detected in affected skin. The eruption resolved after treatment with acitretin and reduction of mycophenolate mofetil dose. Skin biopsies revealed moderate infiltration of macrophages, Langerhans cells, and CD4+ T cells in pre-treatment skin, with notable CD8+ T cell infiltration evident only post-treatment. Symptom resolution correlated with cessation of viral protein expression and emergence of HPyV7-neutralizing antibodies. Shotgun metagenomic sequencing of skin swabs revealed that >99.9% of non-human reads were HPyV7 pre- and post-treatment. However, the relative abundance of viral transcripts in a post-treatment skin biopsy decreased 940-fold compared to pre-treatment, supporting a pathogenic role for viral gene expression. Additionally, DNA and RNA sequencing revealed a putative agnoprotein in the HPyV7 genome with numerous insertion-deletion mutations. One 8bp-deletion variant was more abundantly expressed in highly affected skin, suggesting the presence of active vs dormant viral populations. DNA from a previously reported HPyV7 dermatitis case revealed similar sequence variants, while viromes from 20 volunteers with asymptomatic HPyV7 colonization lacked similar variants. The antiviral DNA cytosine deaminase, APOBEC3B, was significantly upregulated in affected skin, and the observed mutations were consistent with APOBEC activity, suggesting that APOBEC3B may play a role in viral evolution in diseased skin. This study begins to uncover the complex host-pathogen dynamics that produce HPyV7-associated pathology.