Exploring the Diversity of the Human Blood Virome

Abstract

Metagenomics is greatly improving our ability to discover new viruses, as well as their possible associations with disease. However, metagenomics has also changed our understanding of viruses in general. The vast expansion of currently known viral diversity has revealed a large fraction of non-pathogenic viruses, and offers a new perspective in which viruses function as important components of many ecosystems. In this vein, studies of the human blood virome are often motivated by the search for new viral diseases, especially those associated with blood transfusions. However, these studies have revealed the common presence of apparently non-pathogenic viruses in blood, particularly human anelloviruses and, to a lower extent, human pegiviruses (HPgV). To shed light on the diversity of the human blood virome, we subjected pooled plasma samples from 587 healthy donors in Spain to a viral enrichment protocol, followed by massive parallel sequencing. This showed that anelloviruses were clearly the major component of the blood virome and showed remarkable diversity. In total, we assembled 332 complete or near-complete anellovirus genomes, 50 of which could be considered new species. HPgV was much less frequent, but we, nevertheless, recovered 17 different isolates that we subsequently used for characterizing the diversity of this virus. In-depth investigation of the human blood virome should help to elucidate the ecology of these viruses, and to unveil potentially associated diseases.

The plasma virome in longitudinal samples from pregnant patients

“…Nucleic acid from DNA and RNA viruses, including members of the Anelloviridae, Herpesviridae, Flaviridae , and others, are common in peripheral blood ( Popgeorgiev et al., 2013 ; Furuta et al., 2015 ; Rascovan et al., 2016 ; Moustafa et al., 2017 ). Many viruses in the blood have unclear pathogenicity, although some evidence of their association with clinical conditions has been recently reported ( Kaczorowska and van der Hoek, 2020 ; Cebria-Mendoza et al., 2021a ; Stapleton et al., 2011 ; Fama et al., 2020 ; Kyathanahalli et al., 2021 ). This evidence raises the possibility of vertical transmission of the highly prevalent blood viruses to the fetus during pregnancy ( Racicot and Mor, 2017 ; Yu et al., 2022 ).…”

Human Anelloviruses: Influence of Demographic Factors, Recombination, and Worldwide Diversity

“…Partial ORF1 sequences were not discarded, as they included a coding region of at least 500 amino acids. A phylogenetic analysis was then carried out including the previously proposed reference species ( 15 ) and the newly described ORF1 sequences. This allowed assignment of contigs as belonging to TTV, TTMV, or TTMDV genera (197, 88, and 64 sequences, respectively) ( Fig.…”

“…Anelloviruses are an ancient family characterized by a vast diversity ( 16 ), and recently, thousands of human anellovirus sequences have been deposited in databases ( 14 – 16 ). It is therefore appropriate to quantify the current diversity of human anelloviruses.…”

“…TTV, TTMV, and TTMDV have been subdivided into 26, 38, and 15 species, respectively, and these numbers are expected to increase considerably as more isolates are identified ( 12 , 13 ). Recent metagenomics studies have identified thousands of complete or nearly complete anellovirus genomes ( 14 – 16 ). These findings have confirmed the extraordinary diversity of anelloviruses, compared to other human viruses, with recombination playing a major role ( 16 ).…”

Metagenomic analysis of the virome of pooled plasma from healthy blood donors

“…More detailed studies are needed to evaluate if anellovirus might exert pathogenic effect. At present, anelloviruses are still considered part of the natural human virome because of their high prevalence and largely asymptomatic persistence [21].…”