show Abstracthide AbstractDedicator of cytokinesis 8 (DOCK8) deficiency is a rare autosomal recessive, combined immunodeficiency that features cutaneous viral-associated manifestations, including molluscum contagiosum, herpesvirus infections, and warts (HPV infections) along with atopic dermatitis. We present a comprehensive investigation of the skin microbiome of DOCK8-deficient patients, focusing on the skin virome. We utilized both reference-based and reference-free analyses to investigate the microbial (viral) 'dark matter' and discovered a large number of novel human papillomavirus genomes.