The blood DNA virome in 8,000 humans

Abstract

The characterization of the blood virome is important for the safety of blood-derived transfusion products, and for the identification of emerging pathogens. We explored non-human sequence data from whole-genome sequencing of blood from 8,240 individuals, none of whom were ascertained for any infectious disease. Viral sequences were extracted from the pool of sequence reads that did not map to the human reference genome. Analyses sifted through close to 1 Petabyte of sequence data and performed 0.5 trillion similarity searches. With a lower bound for identification of 2 viral genomes/100,000 cells, we mapped sequences to 94 different viruses, including sequences from 19 human DNA viruses, proviruses and RNA viruses (herpesviruses, anelloviruses, papillomaviruses, three polyomaviruses, adenovirus, HIV, HTLV, hepatitis B, hepatitis C, parvovirus B19, and influenza virus) in 42% of the study participants. Of possible relevance to transfusion medicine, we identified Merkel cell polyomavirus in 49 individuals, papillomavirus in blood of 13 individuals, parvovirus B19 in 6 individuals, and the presence of herpesvirus 8 in 3 individuals. The presence of DNA sequences from two RNA viruses was unexpected: Hepatitis C virus is revealing of an integration event, while the influenza virus sequence resulted from immunization with a DNA vaccine. Age, sex and ancestry contributed significantly to the prevalence of infection. The remaining 75 viruses mostly reflect extensive contamination of commercial reagents and from the environment. These technical problems represent a major challenge for the identification of novel human pathogens. Increasing availability of human whole-genome sequences will contribute substantial amounts of data on the composition of the normal and pathogenic human blood virome. Distinguishing contaminants from real human viruses is challenging.

Rapid identification of human‐infecting viruses

“…A total of 14,242,328 viral reads and 396 viral contigs were obtained from Moustafa's study (Moustafa et al, ). Each read or contig was queried against the viral sequences from databases of NCBI RefSeq and Virus‐Host DB by blastn and blastx, and the viruses with the best blast hit from the human‐infecting viruses were considered as human‐infecting viruses.…”

Known unknowns: how might the persistent herpesvirome shape immunity and aging?

“…Using a viromic approach, whole genome sequencing from the blood of uninfected donors readily detects multiple human herpesvirus strains [63]. The frequency of cells carrying latent CMV has been estimated at ~1 in 10 4–5 peripheral blood mononuclear cells (PBMCs), with ~10 viral copies per latently infected cell [64].…”

Metagenomics in pooled plasma, with identification of potential emerging infectious pathogens

“…In conclusion, the results showed us a thought‐provoking discovery of DNA fragments of some pathogens that might threaten blood safety. Despite the discovery of DNA contamination in both commercial reagents and those of environmental origin, the transfusion‐transmissible microbiome results encourage regulation of screening strategies on donor recruitment in certain epidemic areas or seasons to ensure blood safety . Besides the defect of PCR sequencing that could not distinguish dead or alive pathogens, more metagenomics investigation on qualified donations should be encouraged and further investigations such as bacteria culture should be performed to determine whether that pathogen is infectious.…”