Transmission Dynamics of Human Herpesviruses and Other Blood DNA Viruses from Whole Genome Sequences of Families

While hundreds of thousands of human whole genome sequences (WGS) have been collected in the effort to better understand genetic determinants of disease, these whole genome sequences have rarely been used to study another major determinant of human health: the human virome. Using the unmapped reads from WGS of 1,000 families, we present insights into the human blood DNA virome. In addition to extensively cataloguing the viruses detected in WGS of human whole blood and lymphoblastoid cell lines, we use the family structure of our dataset to show that household drives transmission of many microbes. We also identify several cases of inherited chromosomally integrated herpes 6A and 6B and locate candidate integration sequences for these cases. We document genetic diversity within exogenous and integrated HHV species and within integration sites of HHV-6. Finally, in the first observation of its kind, we present evidence that suggests widespread de novo HHV-6B integration and HHV-7 episome replication in lymphoblastoid cell lines. These findings show that the unmapped read space of WGS may be a promising avenue for virology research. ### Competing Interest Statement The authors have declared no competing interest.