
1. Structure and Genome
Anelloviridae are non-enveloped viruses with an icosahedral capsid, featuring a unique circular, single-stranded DNA genome of 3000–4000 nucleotides. This genome encodes at least two key open reading frames (ORFs): ORF1, which likely produces capsid and replication-associated proteins, and ORF2, which may suppress immune pathways like NF-κB. High GC content in non-coding regions forms complex secondary structures that regulate replication. These viruses depend entirely on host nuclear polymerases, using the rolling circle replication method to generate double-stranded intermediates before synthesizing new genomes.

2. Clinical Significance and Transmission
Anelloviridae are detected in over 90% of the global population, often establishing persistent infections from the first month of life. Transmission occurs through maternal routes, saliva droplets, and sexual contact. Despite their prevalence, they remain asymptomatic, with no definitive disease link. Viral loads tend to rise during immunosuppression, hinting at interactions with host immunity. Their vast genetic diversity—spanning over 200 species—indicates an evolutionary success that is still being explored.

3. Research Frontiers
While not associated with specific diseases, Anelloviridae may influence immune responses and act as cofactors in certain conditions. Current studies focus on their replication strategies, host interactions, and potential immunomodulatory roles. Understanding these dynamics could unveil critical insights into persistent infections, viral evolution, and therapeutic opportunities. With their silent yet widespread presence, Anelloviridae remain a compelling target for virology and immunology research.