Unraveling the skin virome of DOCK8-deficient patients

Authors

• O Tirosh
• S Conlan
• C Deming
• NISC Comparative Sequencing Program
• C Ng
• S Lee-Lin
• JA Segre
• HH Kong

Abstract

DOCK8 (dedicator of cytokinesis 8) mutations underlie a rare autosomal recessive form of primary immunodeficiency. DOCK8 protein is involved in the activation of Rho-family GTPases, which are crucial for diverse cell functions. However, DOCK8 is highly expressed in immune cells; consequently, deficient patients manifest with multiple immune system abnormalities. These patients exhibit persistent viral infections of the skin, atopic dermatitis, allergies and skin and hematopoietic malignancies. The high incidence of viral lesions on DOCK8-deficient patients’ skin led us to investigate the virome, or viral component of their skin microbiome, to gain insight into disease pathogenesis. To study the DNA viral community of DOCK8-deficient patients, we deployed shotgun metagenomics to clinical skin samples taken from different body sites. This method allowed us to explore the components of the skin microbiome in an unbiased fashion. DOCK8 patients exhibit a high relative abundance of viral reads in skin samples, compared to matching healthy volunteers. Our analyses reveal that the DNA virus community on patients’ skin is dominated by human papillomaviruses (HPVs), molluscum contagiosum virus, human polyomaviruses and bacterial phages. Using computational tools, such as de-novo assembly, we could also identify possible novel HPVs. Preliminary probing of RNA virus community, using RNA-seq, enabled us to identify, for the first time, the presence of several human RNA viruses on the skin. Our goal is to develop comprehensive datasets to explore more broadly the viral diversity that can colonize and infect human skin.

Scientific Focus Area: Genetics and Genomics

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