Host control and regulation of human anellovirus persistence

Anellovirus persistence in humans is linked to 121 host genetic loci, with NF-kB signaling regulation as the predominant pathway across over 1.1 million participants.

• Why it matters: Although anelloviruses persist lifelong and are highly abundant, the host determinants shaping their physiologic distribution and abundance are unclear.
• What they did: The authors built a pangenome of 2,023 strains and ran genome-wide association studies in >1.1 million participants from three genetic biobanks, then integrated immune-linked detection patterns and single-cell transcription screening.
• The result: They found myeloid progenitors in bone marrow as a prominent in vivo transcription site and showed Perturb-seq that anellovirus ORF2, especially from Alphatorquevirus, attenuates TNF-a–induced NF-kB signaling.

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