Role of BK polyomavirus (BKV) and Torque teno virus (TTV) in liver transplant recipients with renal impairment

Herrmann, Anke; Sandmann, Lisa; Adams, Ortwin; Herrmann, Dominik; Dirks, Miriam; Widera, Marek; Westhaus, Sandra; Kaiser, Rolf; Cristanziano, Veronica Di; Manns, Michael P.; Korth, Johannes; Richter, Nico; Anastasiou, Olympia E.; Timm, Jörg; Hahn, Thomas von; Ciesek, Sandra

doi:10.1099/jmm.0.000823

Cited by 25 publications

(29 citation statements)

References 37 publications

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“…Virological parameters such as the HBV and TTV viral load and HBV genotype were not associated with the development of ALF in our cohort. TTV has been proposed as a novel biomarker of the efficacy of immunosuppression in some but not all patient cohorts [6,7]. In a previous study, for example, TTV levels failed to predict immune-related clinical events [23].…”

Section: Discussionmentioning

confidence: 99%

“…TTV viral loads were determined by an in house real-time PCR with valid ring test certificate (QCMD). The assay was performed on a Rotor-Gene Q instrument (Qiagen, Hilden, Germany) using a standard curve TTV genotype 1a DNA (AB017610.1) cloned in a pCR2.1 vector as described previously [6].…”

Section: Methodsmentioning

confidence: 99%

“…Immunosuppression is, however, a vague term and it is often difficult to assess its degree in patients under immunosuppressive treatment. The presence of circular ssDNA genome of the Teno torque virus (TTV), which is by itself asymptomatic and not associated with clinical diseases, has been proposed as a novel surrogate biomarker for the efficacy of immunosuppression in different patient cohorts and is even used to guide the level of immunosuppression in lung transplant recipients [6,7].…”

Section: Introductionmentioning

confidence: 99%

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Clinical and Virological Aspects of HBV Reactivation: A Focus on Acute Liver Failure

Anastasiou

Theissen

Verheyen

et al. 2019

Viruses

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Hepatitis B virus (HBV) reactivation in immunosuppressed patients can cause considerable morbidity and mortality. The aim of our study was to evaluate factors associated with acute liver failure (ALF) in HBV reactivation. Clinical, laboratory, and virological data of 87 patients with HBV reactivation were analyzed retrospectively. Teno torque virus (TTV) plasma loads were measured as a measure of immune competence. HBV genomes isolated from 47 patients were analyzed by next-generation sequencing. A functional analysis of identified HBsAg mutants was performed. In patients with ALF the diagnosis was significantly later confirmed than in the non-ALF group. Patients diagnosed during immunosuppression had a milder clinical course compared to later diagnosed patients (p = 0.018, OR = 4.17). TTV viral loads did not differ significantly between the two groups. The HBV genomes isolated from ALF patients had higher viral complexity. A mutation in C-region of HBsAg (L216*), was associated with reduced HBsAg production and secretion. Patients diagnosed with HBV reactivation during immunosuppression had a milder clinical course compared to patients diagnosed during immune reconstitution. ALF was associated with higher viral complexity. An HBsAg mutation (L216*) was found to be more frequent in ALF patients and was associated with reduced HBsAg production and secretion.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Clinical and Virological Aspects of HBV Reactivation: A Focus on Acute Liver Failure

Anastasiou

Theissen

Verheyen

et al. 2019

Viruses

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“…It has been proposed that TTV and BKPyV would replicate in the same urothelial cells and use the same cellular machinery in a competitive way, leading to lower serum TTV DNA levels in liver transplant recipients with BKPyV viruria. 8 Handala et al retrospectively analyzed 116 recipients in which BKPyV loads were assessed monthly for the first six months and every three months thereafter. The authors found no differences in plasma TTV DNA levels throughout the first three months between patients with or without BKPyV replication, nor did they observe a correlation between the kinetics of both viruses.…”

Section: Early Kinetics Of Torque Teno Virus Dna Load and Bk Polyomavmentioning

confidence: 99%

Early kinetics of Torque Teno virus DNA load and BK polyomavirus viremia after kidney transplantation

Fernández‐Ruiz

Albert

Giménez

et al. 2020

Transplant Infectious Dis

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Although caution should be exerted when interpreting the above findings due to the single-center design of our study and the absence of cases of biopsy-proven BKPyVAN, the present experience would preliminarily suggest that early post-transplant TTV kinetics may inform about the individual risk of BKPyV viremia in KT recipients. Regular monitoring of TTV DNA levels would serve as a comprehensive surrogate for post-transplant immunocompetence and the associated susceptibility to other iRAEs, thus offering practical advantages over the sole assessment of BKPyV replication. 4 Moreover, the feasibility of such an approach is supported by the recent advent of commercial real-time PCR assays targeting a highly conserved segment (5′ untranslated region) of the viral genome, with the potential for a rapid turnaround time. 6 Our research must be considered as hypothesis-generating, and external validation studies on larger mul-

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“…Papilloma- and polyomaviruses are also known to be associated with cancers, which may preclude their use as replicating vectors. The essentially ubiquitous ssDNA torque teno viruses are potentially associated with some human disease conditions, although causation is not proven [38,39].…”

Section: Future Possibilities For Enhanced Dna Vaccine or Expressimentioning

confidence: 99%

Use of a Novel Enhanced DNA Vaccine Vector for Preclinical Virus Vaccine Investigation

Chapman

Rybicki

2019

Vaccines

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DNA vaccines are stable, safe, and cost effective to produce and relatively quick and easy to manufacture. However, to date, DNA vaccines have shown relatively poor immunogenicity in humans despite promising preclinical results. Consequently, a number of different approaches have been investigated to improve the immunogenicity of DNA vaccines. These include the use of improved delivery methods, adjuvants, stronger promoters and enhancer elements to increase antigen expression, and codon optimization of the gene of interest. This review describes the creation and use of a DNA vaccine vector containing a porcine circovirus (PCV-1) enhancer element that significantly increases recombinant antigen expression and immunogenicity and allows for dose sparing. A 172 bp region containing the PCV-1 capsid protein promoter (Pcap) and a smaller element (PC; 70 bp) within this were found to be equally effective. DNA vaccines containing the Pcap region expressing various HIV-1 antigens were found to be highly immunogenic in mice, rabbits, and macaques at 4–10-fold lower doses than normally used and to be highly effective in heterologous prime-boost regimens. By lowering the amount of DNA used for immunization, safety concerns over injecting large amounts of DNA into humans can be overcome.

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Role of BK polyomavirus (BKV) and Torque teno virus (TTV) in liver transplant recipients with renal impairment

Abstract: Our data indicate that the detection of BKV and TTV is not a risk factor for renal impairment after LT. A correlation of TTV and BKV viral load seems to be an indicator for the immune status of the host.

Cited by 25 publications

References 37 publications

Clinical and Virological Aspects of HBV Reactivation: A Focus on Acute Liver Failure

Clinical and Virological Aspects of HBV Reactivation: A Focus on Acute Liver Failure

Early kinetics of Torque Teno virus DNA load and BK polyomavirus viremia after kidney transplantation

Use of a Novel Enhanced DNA Vaccine Vector for Preclinical Virus Vaccine Investigation

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