Torquetenovirus: the human virome from bench to bedside

Focosi, Daniele; Antonelli, Guido; Pistello, Mauro; Maggi, Fabrizio

doi:10.1016/j.cmi.2016.04.007

Cited by 195 publications

(267 citation statements)

References 48 publications

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“…13,15,39,44 Transplant recipients with episodes of organ rejection have been shown to have lower Anelloviridae levels than those without rejection, consistent with inadequate immune suppression. 14,16 Our data are consistent with previous findings in blood. 14,16 Our data are consistent with previous findings in blood.…”

Section: Discussionsupporting

confidence: 93%

“…9 Anelloviridae are a family of highly diverse, nonenveloped, small circular single-stranded DNA (ssDNA) viruses that infect humans and other mammals. 14,16,17 Whether lung allograft rejection might be associated with low Anelloviridae levels within the lung itself, perhaps as an indicator of local immune function, has not been investigated. [10][11][12] Anelloviridae are likely under chronic immune control, given that levels in blood increase in immunosuppressed states.…”

Section: Introductionmentioning

confidence: 99%

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Bidirectional transfer of Anelloviridae lineages between graft and host during lung transplantation

Abbas

Young

Clarke

et al. 2019

American Journal of Transplantation

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Solid organ transplantation disrupts virus-host relationships, potentially resulting in viral transfer from donor to recipient, reactivation of latent viruses, and new viral infections. Viral transfer, colonization, and reactivation are typically monitored using assays for specific viruses, leaving the behavior of full viral populations (the "virome") understudied. Here we sought to investigate the temporal behavior of viruses from donor lungs and transplant recipients comprehensively. We interrogated the bronchoalveolar lavage and blood viromes during the peritransplant period and 6-16 months posttransplant in 13 donor-recipient pairs using shotgun metagenomic sequencing. Anelloviridae, ubiquitous human commensal viruses, were the most abundant human viruses identified. Herpesviruses, parvoviruses, polyomaviruses, and bacteriophages were also detected. Anelloviridae populations were complex, with some donor organs and hosts harboring multiple contemporaneous lineages. We identified transfer of Anelloviridae lineages from donor organ to recipient serum in 4 of 7 cases that could be queried, and immigration of lineages from recipient serum into the allograft in 6 of 10 such cases. Thus, metagenomic analyses revealed that viral populations move between graft and host in both directions, showing that organ transplantation involves implantation of both the allograft and commensal viral communities.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Bidirectional transfer of Anelloviridae lineages between graft and host during lung transplantation

Abbas

Young

Clarke

et al. 2019

American Journal of Transplantation

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“…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 [10–12]. Metagenomic studies also lead to the identification of novel RNA viruses—for example the identification of two rhabdoviruses [13].…”

Section: Introductionmentioning

confidence: 99%

The blood DNA virome in 8,000 humans

Moustafa¹,

Xie²,

Kirkness³

et al. 2017

PLoS Pathog

272

258

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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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“…3 As a consequence, various biomarkers with or without antigenic specificity have been proposed, with most of them not having yet reached clinical maturity. 6 Torque teno virus (TTV), first isolated in 1997 from a Japanese patient with posttransfusion hepatitis, 7 constitutes the prototype member within the Anelloviridae family. 5 Anelloviruses are small, nonenveloped, single-stranded DNA viruses with a circular, negative-sense genome.…”

Section: Introductionmentioning

confidence: 99%

Monitoring of alphatorquevirus DNA levels for the prediction of immunosuppression-related complications after kidney transplantation

Fernández‐Ruiz

Albert

Giménez

et al. 2019

American Journal of Transplantation

117

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The replication kinetics of nonpathogenic anelloviruses belonging to the Alphatorquevirus genus (such as torque teno virus) might reflect the overall state of posttransplant immunosuppression. We analyzed 221 kidney transplant (KT) recipients in whom plasma alphatorquevirus DNA load was quantified by real-time polymerase chain reaction at baseline and regularly through the first 12 posttransplant months. Study outcomes included posttransplant infection and a composite of opportunistic infection and/or de novo malignancy (immunosuppression-related adverse event [iRAE]). Alphatorquevirus DNA loads at month 1 were higher among patients who subsequently developed posttransplant infection (P = .023) or iRAE (P = .009). Likewise, those with iRAE beyond months 3 and 6 also exhibited higher peak viral loads over the preceding periods. Areas under the curve for log 10 alphatorquevirus DNAemia estimated by months 1 or 6 were significantly higher in patients experiencing study outcomes. Alphatorquevirus DNA loads above 3.15 and 4.56 log 10 copies/mL at month 1 predicted the occurrence of posttransplant infection (adjusted hazard ratio [aHR]: 2.88; 95% confidence interval [CI]: 1.13-7.36; P = .027) and iRAE (aHR: 5.17; 95% CI: 2.01-13.33; P = .001). In conclusion, posttransplant monitoring of plasma alphatorquevirus DNA kinetics may be useful to identify KT recipients at increased risk of immunosuppression-related complications. K E Y W O R D S biomarker, clinical research/practice, complication: infectious, complication: malignant, infection and infectious agents, infection and infectious agents -viral, infectious disease, kidney transplantation/nephrology

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Torquetenovirus: the human virome from bench to bedside

Cited by 195 publications

References 48 publications

Bidirectional transfer of Anelloviridae lineages between graft and host during lung transplantation

Bidirectional transfer of Anelloviridae lineages between graft and host during lung transplantation

The blood DNA virome in 8,000 humans

Monitoring of alphatorquevirus DNA levels for the prediction of immunosuppression-related complications after kidney transplantation

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