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.
Highlights
Research on the human microbiome has been primarily directed to the prokaryotic composition of the human microflora
Sex, and age were important determinants of viral prevalence. This large study calls attention on the challenge of interpreting generation sequencing data for the identification of novel viruses. It serves to categorize the abundance of human DNA viruses using an unbiased technique
Analysis of the whole human genome by next-generation sequencing is an exercise in metagenomics: after mapping sequencing reads to the human reference genome, there is a significant proportion that is left uncharacterized [1]
Summary
Research on the human microbiome has been primarily directed to the prokaryotic composition of the human microflora. Previous studies of the human virome have addressed the viral component of the gut flora [2,3,4] and skin [5,6,7], with particular attention to the very abundant bacteriophages [7, 8]. Many viruses are present in peripheral blood —in particular, members of the Herpesviridae and Anelloviridae families are identified in the absence of disease. Metagenomic studies on blood have identified great genetic diversity of anelloviruses [10,11,12]. Other viral sequences in the blood of healthy individuals are related to members of the Picornaviridae, Poxviridae, Flaviviridae, and Phycodnaviridae families (reviewed in [9]). A number of viruses, prominently retroviruses, are integrated in the human genome as provirus, while others may integrate occasionally or accidentally [14]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
