Human anelloviruses, companions in a lifelong journey

Viruses have historically been described as a piece of bad news wrapped up in protein. Yet, viruses discovered more recently, often found by chance, have been shown to exhibit a relationship with humans that is less strictly parasitic than traditionally thought. The growing interest in non-pathogenic viruses has led to a focus on the healthy human virome, which refers to the total composition of viruses present in a healthy human body. Within the human virome, anelloviruses, members of the Anelloviridae family, are perhaps the most fascinating and often describes as one of the friendliest viruses known. These viruses chronically infect the vast majority of the human population, reaching near 100% prevalence, and dominate in blood. Each individual carries a personal set of members belonging to this genetically diverse family, defined as the anellome, that stay with us throughout life without causing any disease. Anelloviruses are among the most mysterious viruses to date, due to absence of robust culture systems or animal models, and their biological significance is unknown. In this thesis, several fundamental knowledge gaps are addressed. In part 1, anellovirus colonization, potential transmission routes and their source in early-life are investigated, and in part 2 anellovirus-host interactions, particularly the innate immunity, are examined for their contribution to virus control. Overall, much remains to be learned from these tiny companions in our lifelong journey.