Global genome analysis reveals a vast and dynamic anellovirus landscape within the human virome

Arze, Cesar; Springer, Simeon; Dudas, Gytis; Patel, Sneha; Bhattacharyya, Agamoni; Swaminathan, Harish; Brugnara, Carlo; Delagrave, Simon; Ong, Tuyen; Kahvejian, Avak; Echelard, Yann; Weinstein, Elena; Hajjar, Roger J.; Andersen, Kristian G.; Yozwiak, Nathan L.

doi:10.1016/j.chom.2021.07.001

Cited by 70 publications

(136 citation statements)

References 82 publications

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“…Anelloviruses are an ancient family characterized by a vast diversity [49], and it is believed that their evolution has followed that of the animals they infect [50,51]. In primates, this coevolution hypothesis was questioned since human and chimpanzee isolates did not group phylogenetically according to host species [44], except in the case of TTMDV, whose divergence has been proposed following the speciation of humans and chimpanzees.…”

Section: Discussionmentioning

confidence: 99%

Exploring the Diversity of the Human Blood Virome

Cebriá-Mendoza

Bracho

Arbona

et al. 2021

Viruses

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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.

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Section: Discussionmentioning

confidence: 99%

Exploring the Diversity of the Human Blood Virome

Cebriá-Mendoza

Bracho

Arbona

et al. 2021

Viruses

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“…Phylogenetic analysis of TTV isolates recovered from disparate locations have identified 7 major clusters, with genomic sequence differences of up to 35% (90). It has been hypothesized that in a given individual, genetic variability within a viral group is high, and that coinfection by distinct viral strains in blood and other tissues is common (91,92). A study investigated possible relationships between the number of genogroups carried and the total TTV load present in 239 TTVpositive subjects (93).…”

Section: Genetic Heterogeneitymentioning

confidence: 99%

“…Taking advantage of these regions, nested and semi-nested PCR assays are developed in which the genomic DNA of all anelloviruses is amplified by first-round PCR with universal primers, and then species-specific DNA are amplified by using a second set of primers (7). In a number of studies, sequences spanning N22-ORF1 regions are utilized for the detection of anellovirus DNA (11,92). However, this strategy allows detection of only some genotypes of TTV, a genus with more than 30 genotypes (95).…”

Section: Detection and Quantitation Of Anellovirusesmentioning

confidence: 99%

“…In the majority of human body sites, microbial diversity is considered a signature of health (1). If multiple variants or genotypes of anellovirus ("anellome") found in healthy humans remain stable for a long time, they may make up the personalized and healthy part of the host microbiome (92). The gene products of anellovirus might help to maintain the composition and fitness of other (beneficial) microbial communities by preventing colonization by pathogens.…”

Section: A Mechanism By Which Anellovirus Colonization Could Influence the Timing Of Parturitionmentioning

confidence: 99%

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Human Anelloviruses: Prevalence and Clinical Significance During Pregnancy

2021

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Although the bacterial microbiota of various compartments (e.g. vagina, amniotic fluid, and placenta) have been studied in pregnancy, there has been far less emphasis on normal and pathological viral communities. Cumulative evidence shows the presence of a number of apathogenic viruses in various tissues of healthy people, including pregnant individuals. What role, if any, these viruses play in human physiology is unknown. Anelloviruses (family Anelloviridae) are circular, single-stranded DNA viruses commonly detected with high prevalence in vertebrate hosts, including primates. Humans are nearly always colonized with at least 1 of 3 anellovirus subtypes, namely Alphatorquevirus (torque teno virus, TTV), Betatorquevirus (torque teno midi virus, TTMDV), and Gammatorquevirus (torque teno mini virus, TTMV). In healthy pregnant people, the prototype anellovirus, TTV, has been found in maternal and (variably) fetal blood, amniotic fluid, cervical and vaginal secretions, breast milk, and saliva. Nonetheless, the relevance of human anelloviruses in pregnancy and labor is unclear. There is evidence suggesting a link between anellovirus colonization and preterm birth. In this review, we discuss what is known about this family of commensal viruses in health and disease, and specifically the roles they might play during pregnancy and in the timing of delivery.

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“…Anelloviruses make up the bulk of the viral load in healthy humans and demonstrate broad tissue tropism (De Vlaminck et al, 2013; Spandole et al, 2015). Infections with anelloviruses are ubiquitous, occur early in life and persist into adulthood, with each individual harboring a unique, personal “anellome” (Arze et al, 2021; Kaczorowska and van der Hoek, 2020). Despite increased viral load being associated with diseases such as hepatitis and cancer, no study thus far has shown evidence for their causal involvement in any disease (Kaczorowska and van der Hoek, 2020).…”

Section: Introductionmentioning

confidence: 99%

Comprehensive profiling of antibody responses to the human anellome using programmable phage display

Venkataraman

Swaminathan

Arze

et al. 2022

Preprint

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Viruses belonging to the diverse Anelloviridae family represent a major constituent of the commensal human virome. Aside from their widespread prevalence and persistence in humans and their absence of detectable pathologic associations, little is known about the immunobiology of the human anellome. In this study, we employed the Phage ImmunoPrecipitation Sequencing (PhIP-Seq) assay for comprehensive analyses of antibody binding to 56 amino acid long anellovirus peptides. We designed and constructed a large and diverse "AnelloScan" T7 phage library comprising more than 32,000 non-redundant peptides representing the ORF1, ORF2, ORF3 and TTV-derived apoptosis-inducing protein (TAIP) sequences of more than 800 human anelloviruses (spanning three genera). We used this library to profile the antibody reactivities of serum samples from 156 subjects. The vast majority of anellovirus peptides were not reactive in any of the subjects tested (n=~28,000; ~85% of the library). Antibody reactive peptides were largely restricted to the C-terminal region of the putative capsid protein, ORF1. To characterize antibody responses to newly acquired anellovirus infections, we screened a longitudinal cohort of matched blood-transfusion donors and recipients. Most transmitted anelloviruses did not elicit detectable antibody reactivity in the recipient (29 out of a total of 40 transmitted anelloviruses) and the remainder demonstrated delayed reactivity (~100-150 days after transfusion). This study represents the first large-scale epitope-level serological survey of the antibody response to the human anellome.

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Global genome analysis reveals a vast and dynamic anellovirus landscape within the human virome

Cited by 70 publications

References 82 publications

Exploring the Diversity of the Human Blood Virome

Exploring the Diversity of the Human Blood Virome

Human Anelloviruses: Prevalence and Clinical Significance During Pregnancy

Comprehensive profiling of antibody responses to the human anellome using programmable phage display

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