Expanded skin virome in DOCK8-deficient patients.

Area of Science:

• Immunology
• Virology
• Microbiome Research

Background:

• Healthy skin harbors a low viral load, primarily bacteriophages.
• Eukaryotic viruses are linked to skin diseases, but skin viromes are poorly characterized.
• Primary immunodeficiencies offer insights into host-microbe interactions, particularly in skin infections.

Purpose of the Study:

• To investigate the impact of Dedicator of cytokinesis 8 (DOCK8) deficiency on the skin virome.
• To characterize eukaryotic viral communities in DOCK8-deficient individuals compared to healthy controls.

Main Methods:

• Deep metagenomic sequencing of skin samples from DOCK8-deficient patients and healthy volunteers.
• Bioinformatic analysis, including de novo assembly, to identify and characterize viral genomes.
• Comparative analysis of viral diversity and representation between patient and control groups.

Main Results:

• DOCK8-deficient skin samples showed significantly higher eukaryotic viral representation and diversity than healthy skin.
• Hundreds of novel human papillomavirus genomes were identified using de novo assembly.
• The findings suggest an expansion of the skin virome in the absence of functional DOCK8.

Conclusions:

• Immune surveillance is crucial for controlling eukaryotic viral colonization on the skin.
• DOCK8 deficiency impairs the immune system's ability to regulate the skin virome.
• This research sheds light on previously unknown viral communities in the skin microbiome.