044 Metatranscriptomics reveals association of α-, β-, and γ-HPVs with typical epidermodysplasia verruciformis in a large cohort of patients with CIB1, TMC6, or TMC8 mutations

Cutaneous human papillomavirus (HPV) infection typically manifests with isolated warts. However, some patients in familial clustering develop extensive and protracted HPV infections, primarily the β-HPV types 5 8, distinct cutaneous findings. This clinical entity, epidermodysplasia verruciformis (EV), autosomal recessive inheritance, is characterized by numerous flat warts childhood, which progress into squamous cell carcinomas later life. The “typical” form of EV, not vulnerable to other caused mutations CIB1, TMC6, or TMC8, impair keratinocyte-intrinsic immunity infection. Mutations genes related T-cell development function, have been associated “atypical” EV infections. We developed a whole-transcriptome sequencing-based method on RNA from skin biopsies for concomitant detection viral genetic determinants wart lesions cohort 50 patients. method, VirPy, can detect 926 viruses, including more than 400 HPVs, corresponding mutations. Nine TMC8 (n=2), TMC6 (n= 5) CIB1 (n=2) 12 families, 14 were detected. most predominant this was HPV14. In addition, RNA-seq data examined variant prioritization, pathogenicity confirmation, expression profiling. Besides, we identified total 20 different HPVs 16 β-, three α- one γ-HPV(HPV128) patient mutation. summary, utilization RNA-Seq as first-tier diagnostic allowed us simultaneously profile transcriptome host mutation exploring consequences variants unknown significance well virome