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      An atlas of the blood virome in healthy individuals

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          Highlights

          • We identified 56 different viruses from 37 viral families, including 25 human DNA, RNA and retroviruses in 70% of the studied pools.

          • Anelloviruses are widely distributed and dominate the blood virome in healthy individuals.

          • Human herpesviruses and GBV-C are commonly prevalent in asymptomatic humans.

          • The prevalence of RNA viruses often causing acute infection, like HEV, HPIV, RSV and HCoV-HKU1, revealing of a transmissible risk of asymptomatic infection.

          • Several viruses possible related to transfusion safety were identified, including human Merkel cell polyomavirus, Papillomavirus, Parvovirus B19 and Herpesvirus 8 in addition to HBV and HIV.

          Abstract

          Emerging evidence indicates that gut virome plays a role in human health and disease, however, much less is known about the viral communities in blood. Here we conducted a direct metatranscriptomic sequencing of virus-like-particles in blood from 1200 healthy individuals, without prior amplification to avoid potential amplification bias and with a strictly bioinformatic and manual check for candidate viral reads to reduce false-positive matches. We identified 55 different viruses from 36 viral families, including 24 human DNA, RNA and retroviruses in 70% of the studied pools. The study showed that anelloviruses are widely distributed and dominate the blood virome in healthy individuals. Human herpesviruses and pegivirus-1 are commonly prevalent in asymptomatic humans. We identified the prevalence of RNA viruses often causing acute infection, like HEV, HPIV, RSV and HCoV-HKU1, revealing of a transmissible risk of asymptomatic infection. Several viruses possible related to transfusion safety were identified, including human Merkel cell polyomavirus, papillomavirus, parvovirus B19 and herpesvirus 8 in addition to HBV. In addition, phages in Caudovirales and Microviridae, were commonly found in pools of samples with a very low abundance; a few sequences for invertebrate, plant and giant viruses were found in some of individuals; however, the remaining 31 viruses mostly reflect extensive contamination from commercial reagents and the work environments. In conclusion, this study is the first comprehensive investigation of blood virome in healthy individuals by metatranscriptomic sequencing of VLP in China. Further investigation of potential false positives representing a major challenge for the identification of novel viruses in mNGS, will offer a systemic idea and means to reveal true viral infections of human.

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          Most cited references35

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          The virome in mammalian physiology and disease.

          The virome contains the most abundant and fastest mutating genetic elements on Earth. The mammalian virome is constituted of viruses that infect host cells, virus-derived elements in our chromosomes, and viruses that infect the broad array of other types of organisms that inhabit us. Virome interactions with the host cannot be encompassed by a monotheistic view of viruses as pathogens. Instead, the genetic and transcriptional identity of mammals is defined in part by our coevolved virome, a concept with profound implications for understanding health and disease. Copyright © 2014 Elsevier Inc. All rights reserved.
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            The human virome: assembly, composition and host interactions

            The human body hosts vast microbial communities, termed the microbiome. Less well known is the fact that the human body also hosts vast numbers of different viruses, collectively termed the ‘virome’. Viruses are believed to be the most abundant and diverse biological entities on our planet, with an estimated 1031 particles on Earth. The human virome is similarly vast and complex, consisting of approximately 1013 particles per human individual, with great heterogeneity. In recent years, studies of the human virome using metagenomic sequencing and other methods have clarified aspects of human virome diversity at different body sites, the relationships to disease states and mechanisms of establishment of the human virome during early life. Despite increasing focus, it remains the case that the majority of sequence data in a typical virome study remain unidentified, highlighting the extent of unexplored viral ‘dark matter’. Nevertheless, it is now clear that viral community states can be associated with adverse outcomes for the human host, whereas other states are characteristic of health. In this Review, we provide an overview of research on the human virome and highlight outstanding recent studies that explore the assembly, composition and dynamics of the human virome as well as host–virome interactions in health and disease.
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              The blood DNA virome in 8,000 humans

              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.
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                Author and article information

                Contributors
                Journal
                Virus Res
                Virus Res
                Virus Research
                Elsevier
                0168-1702
                1872-7492
                17 November 2022
                02 January 2023
                17 November 2022
                : 323
                : 199004
                Affiliations
                [a ]NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, CAMS&PUMC, Beijing 100730, PR China
                [b ]China Institute of Veterinary Drug Control, Beijing 100081, PR China
                Author notes
                [1]

                These authors contributed equally to this work.

                Article
                S0168-1702(22)00333-1 199004
                10.1016/j.virusres.2022.199004
                10194198
                36402209
                a14ffdf0-55d3-4640-b0f1-a2f68b102c82
                © 2022 The Authors. Published by Elsevier B.V.

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                : 22 July 2022
                : 14 October 2022
                : 15 November 2022
                Categories
                Article

                Microbiology & Virology
                virome,blood,metatranscriptomic sequencing,healthy individuals
                Microbiology & Virology
                virome, blood, metatranscriptomic sequencing, healthy individuals

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