Genetic analyses identify 82 loci where common variants influence viral DNA load in blood, with many signals in the MHC (HLA region) for EBV and HHV-7, and strong heritability contributions (e.g., around half for EBV). The ERAP1–ERAP2–LNPEP locus also shows strong associations, driven by different signals for EBV and HHV-7 loads.

The study distinguishes EBV type 1 and type 2 loads in saliva, revealing possible type-specific host–virus interactions and birth-origin effects, with type 2 prevalence varying by birthplace.

Viral DNA loads in blood and saliva are generally low but detectable, with herpesviruses and anelloviruses prominent; saliva exhibits bursts of lytic activity for herpesviruses, while blood reflects latent or cell-associated DNA.

Viral DNA load shows circadian and seasonal patterns, with EBV higher in winter and daily fluctuations for EBV and HHV-7, persisting after adjusting for confounders.

The study uses large datasets to analyze how the human DNA virome in blood and saliva varies with age, sex, ancestry, and genetics, quantifying viral DNA load and its associations with host genetic variation.

HLA alleles show virus- and tissue-specific associations (e.g., HLA-DRB1*04:04 with higher EBV load; HLA-A*02:01 reduces EBV load in blood but not saliva), indicating diverse immune recognition for latent versus lytically active viruses.

Age and sex strongly influence viral DNA load across multiple viruses, with older individuals showing higher EBV and TTV loads in blood, younger individuals higher in HHV-7 and HHV-6B, and men generally having higher loads than women.

An ancestry-specific analysis highlights ACKR1 rs2814778 as contributing to differences in EBV and HHV-7 prevalence between African and European ancestries, partially explaining observed disparities.

Other genes outside the MHC, including BCL, PML, SP110, MX2, TNFRSF13B, FAS, and TBKBP1, implicate roles in viral replication, immune evasion, and apoptosis influencing viral DNA load and persistence.