Plasma DNA levels of Torque teno virus and immunosuppression after lung transplantation

Görzer, Irene; Haloschan, Mats; Jaksch, Péter; Klepetko, Walter; Puchhammer‐Stöckl, Elisabeth

doi:10.1016/j.healun.2013.12.007

Cited by 108 publications

(157 citation statements)

References 7 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. 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.…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies have shown that Anelloviridae are ubiquitous in the human eukaryotic virome. [13][14][15] Lower Anelloviridae burden in blood has been associated with solid organ rejection, suggesting that Anelloviridae DNA copy numbers may be a useful "functional" indicator of immune status. 9 Human Anelloviridae have not been associated with any diseases, although other small circular ssDNA viruses are important veterinary pathogens.…”

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: Discussionmentioning

confidence: 99%

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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“…Thus, local inflammation and leukocyte recruitment to the lung following brain death might result in enhanced TTV replication. Additionally, corticosteroids are generally given to organ donors to modulate inflammation after brain death, and corticosteroid-induced immunosuppression could be another reason for the high TTV levels in donors since host immune function is thought to control virus replication (34, 38, 64). Future studies will be needed to determine whether lung TTVs increase in critically ill patients generally, or if high levels are specifically associated with brain death and/or corticosteroid or other donor treatments.…”

Section: Discussionmentioning

confidence: 99%

The Perioperative Lung Transplant Virome: Torque Teno Viruses Are Elevated in Donor Lungs and Show Divergent Dynamics in Primary Graft Dysfunction

Abbas

Diamond

Chehoud

et al. 2017

American Journal of Transplantation

101

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Primary graft dysfunction (PGD) is a principal cause of early morbidity and mortality after lung transplantation, but its pathogenic mechanisms are not fully clarified. Thus far, studies using standard clinical assays have not linked microbial factors to PGD. We previously used comprehensive metagenomic methods to characterize viruses in lung allografts >1 month post-transplant and found that levels of Anellovirus, mainly Torque teno viruses (TTV), were significantly higher than in non-transplant healthy controls. Here we used quantitative PCR to analyze TTV and shotgun metagenomics to characterize full viral communities in acellular bronchoalveolar lavage from donor organs and post-reperfusion allografts in PGD and non-PGD lung transplant recipient pairs. Unexpectedly, TTV DNA levels were 100-fold elevated in donor lungs compared with healthy adults (p=0.0026). Although absolute TTV levels did not differ by PGD status, PGD cases showed a smaller increase in TTV levels from pre- to post-transplant than did control recipients (p=0.041). Metagenomic sequencing revealed mainly TTV and bacteriophages of respiratory tract bacteria, but no viral taxa distinguished PGD cases from controls. These findings suggest that conditions associated with brain death promote TTV replication, and that greater immune activation or tissue injury associated with PGD may restrict TTV abundance in the lung.

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“…However, a clear link between detection of KIPyV and respiratory symptoms is yet to be established (Bialasiewicz et al, 2007;Hormozdi et al, 2010). TTV viremia has been suggested to correlate with the intensity of immunosuppression, as several recent studies reported a higher level of Anelloviridae (with a predominance of TTV) in transplant recipients with more intense immunosuppression (Burra et al, 2008;De Vlaminck et al, 2013;Focosi et al, 2014;Görzer et al, 2014). Our analysis also reported the presence of some plant viruses such as pepino mosaic virus, which may be due to food uptake, and bacteriophage sequences, which are expected to occur in abundance due to the presence of commensal bacterial species (Table 1).…”

Section: Discussionmentioning

confidence: 99%

Unbiased metagenomic sequencing complements specific routine diagnostic methods and increases chances to detect rare viral strains

Lewandowska

Zagordi

Zbinden

et al. 2015

Diagnostic Microbiology and Infectious Disease

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Multiplex PCR assays for respiratory viruses are widely used in routine diagnostics, as they are highly sensitive, rapid, and cost effective. However, depending on the assay system, cross-reactivity between viruses that share a high sequence homology as well as detection of rare virus isolates with sequence variations can be problematic. Virus sequence-independent metagenomic high-throughput sequencing allows for accurate detection of all virus species in a given sample, as we demonstrate here for human Enterovirus and Rhinovirus in a lung transplant patient. While early in infection a commercial PCR assay recorded Rhinovirus, high-throughput sequencing correctly identified human Enterovirus C104 as the source of infection, highlighting the potential of the technology and the benefit of applying open assay formats in complex diagnostic situations.

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Plasma DNA levels of Torque teno virus and immunosuppression after lung transplantation

Cited by 108 publications

References 7 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 Perioperative Lung Transplant Virome: Torque Teno Viruses Are Elevated in Donor Lungs and Show Divergent Dynamics in Primary Graft Dysfunction

Unbiased metagenomic sequencing complements specific routine diagnostic methods and increases chances to detect rare viral strains

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