Hans H Hirsch

University of Zurich, Zürich, Zurich, Switzerland

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Publications (257)1401.04 Total impact

  • Piotr Kardas · Céline Leboeuf · Hans H Hirsch ·
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    ABSTRACT: Background: Polyomavirus JC (JCPyV) and BK (BKPyV) can cause significant diseases in immunocompromised patients including nephropathy, hemorrhagic cystitis, and leukoencephalopathy. Recently, JCPyV and BKPyV IgG have been explored as risk predictors in multiple sclerosis and transplant patients, but sensitivity, specificity and quantification issues limit current performance. Objective: To improve JCPyV and BKPyV-specific antibody testing. Study design: Healthy blood donor sera (N=400) were tested at dilutions 1:100, 1:200, and 1:400 for JCPyV- and BKPyV-specific IgG using VP1 virus-like particle (VLP)-based ELISAs normalized to a laboratory reference serum. Normalized optical density 492nm greater or equal 0.1 in all 3 dilutions was regarded as reactive. Sera with discordant reactivity in at least one dilution were retested after VLP preadsorption. Results: At dilutions 1:100, 1:200, and 1:400, IgG reactivity was 74%, 60% and 53% for JCPyV, and 93%, 86% and 74% for BKPyV, respectively. At these dilutions, JCPyV-VLP preadsorption identified 56, 4 and 0 false-positives and 0, 4 and 27 false-negatives, respectively. Dilution-dependent sensitivity was 100%, 98%, and 89%, and specificity 65, 98%, and 100%, respectively. For sera diluted 100-, 200-, and 400-fold, BKPyV-VLP preadsorption identified 28, 1 and 0 false-positives, and 0, 0 and 46 false-negatives, and sensitivity was 100%, 100%, 86%, and specificity 50%, 98%, 100%, respectively. Conclusion: For seroepidemiology studies, normalized JCPyV and BKPyV IgG ELISA at 1:200 serum dilution provides optimal sensitivity and specificity with the lowest false-positive and false-negative rate. For individual risk assessment, dilutions of 100, 200, and 400 combined with preadsorption for low-reactive sera may be most appropriate.
    Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 09/2015; 71:28-33. DOI:10.1016/j.jcv.2015.07.305 · 3.02 Impact Factor
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    ABSTRACT: Multidrug-resistant (MDR) cytomegalovirus (CMV) emerged after transient responses to ganciclovir, foscarnet, and cidofovir in a CMV-seropositive recipient who underwent allogeneic hematopoietic stem cell transplantation from a CMV-seronegative donor. Experimental treatments using leflunomide and artesunate failed. Re-transplantation from a CMV-seropositive donor supported by adoptive transfer of pp65-specific T cells and maribavir was followed by lasting suppression. This case illustrates that successful MDR CMV therapy may require individualized multidisciplinary approaches.This article is protected by copyright. All rights reserved.
    Transplant Infectious Disease 08/2015; 17(5). DOI:10.1111/tid.12435 · 2.06 Impact Factor
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    Christiane Beckmann · Hans H. Hirsch ·
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    ABSTRACT: Rapid diagnosis of influenza is important for controlling outbreaks and starting antiviral therapy. Direct antigen detection (DAD) is rapid, but lacks sensitivity, whereas nucleic acid amplification testing (NAT) is more sensitive, but also more time-consuming. To evaluate the performance of a rapid isothermal NAT and two DADs. During February-May 2014, we tested 211 consecutive patients with influenza-like illness using a commercial isothermal NAT (Alere™ Influenza A&B) as well as the DAD Sofia(®) Influenza A+B and BinaxNOW(®) Influenza A&B for detection of influenza-A and -B virus. RespiFinder-22(®) a commercial multiplex NAT served as reference test. Serial 10-fold dilutions of influenza-A and -B cell culture supernatants were examined. Another 225 patient samples were tested during December 2014-February 2015. Compared to RespiFinder-22(®), the isothermal NAT Alere™ Influenza A&B, and the DAD Sofia(®) Influenza A+B and BinaxNOW(®) Influenza A&B had sensitivities of 77.8%, 59.3% and 29.6%, and specificities of 99.5%, 98.9% and 100%, respectively, for the first 211 patient samples. Alere™ Influenza A&B showed 85.7% sensitivity and 100% specificity in the second cohort. Isothermal NAT was 10-100-fold more sensitive compared to DAD for influenza virus culture supernatants with a lower limit of detection of 5000-50,000 copies/mL. The average turn-around time (TAT) of isothermal NAT and DADs was 15min, but increased to 110min for Alere™ Influenza A&B, 30min for BinaxNOW(®) Influenza A&B, and 45min for Sofia(®) Influenza A+B, when analyzing batches of 6 samples. Simple sample processing and a TAT of 15min render isothermal NAT Alere™ Influenza A&B suitable for sequential near-patient testing, but the TAT advantage is lost when testing of larger series. Copyright © 2015 Elsevier B.V. All rights reserved.
    Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 06/2015; 67. DOI:10.1016/j.jcv.2015.03.024 · 3.02 Impact Factor
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    ABSTRACT: Condomless sex is a key driver of sexually transmitted diseases. In this study, we assess the long-term changes (2000–2013) of the occurrence of condomless sex among human immunodeficiency virus (HIV)-infected individuals enrolled in the Swiss HIV Cohort study. The frequencies with which HIV-infected individuals reported condomless sex were either stable or only weakly increasing for 2000–2008. For 2008–2013, these rates increased significantly for stable relationships among heterosexuals and men who have sex with men (MSM) and for occasional relationships among MSM. Our results highlight the increasing public health challenge posed by condomless sex and show that condomless sex has been increasing even in the most recent years.
    06/2015; 2(2). DOI:10.1093/ofid/ofv077
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    ABSTRACT: Natural killer cell function is regulated by inhibitory and activating killer cell immunoglobulin-like receptors (KIR). Previous studies have documented associations of KIR genotype with the risk of cytomegalovirus (CMV) replication after solid organ transplantation. In this study of 649 solid organ transplant recipients, followed prospectively for infectious disease events within the Swiss Transplant Cohort Study, we were interested to see if KIR genotype associated with virus infections other than CMV. We found that KIR B haplotypes (which have previously been linked to protection from CMV replication) were associated with protection from varicella zoster virus infection (hazard ratio, 0.43; 95% confidence interval, 0.21-0.91; P = 0.03). No significant associations were detected regarding the risk of herpes simplex, Epstein-Barr virus or BK polyomavirus infections. In conclusion, these data provide evidence that the relative protection of KIR haplotype B from viral replication after solid organ transplantation may extend beyond CMV to other herpes viruses, such as varicella zoster virus and possibly Epstein-Barr virus.
    Transplantation 06/2015; DOI:10.1097/TP.0000000000000778 · 3.83 Impact Factor
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    ABSTRACT: Prospective cohort studies significantly contribute to answering specific research questions in a defined population. Since 2008, the Swiss Transplant Cohort Study (STCS) systematically enrolled >95 % of all transplant recipients in Switzerland, collecting predefined data at determined time points. Designed as an open cohort, the STCS has included >3900 patients to date, with a median follow-up of 2.96 years (IQR 1.44-4.73). This review highlights some relevant findings in the field of transplant-associated infections gained by the STCS so far. Three key general aspects have crystallized: (i) Well-run cohort studies are a powerful tool to conduct genetic studies, which are crucially dependent on a meticulously described phenotype. (ii) Long-term real-life observations are adding a distinct layer of information that cannot be obtained during randomized studies. (iii) The systemic collection of data, close interdisciplinary collaboration, and continuous analysis of some key outcome data such as infectious diseases endpoints can improve patient care.
    Current Infectious Disease Reports 06/2015; 17(6):486. DOI:10.1007/s11908-015-0486-5 · 1.68 Impact Factor
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    ABSTRACT: Donor PTX3 polymorphisms were shown to influence the risk of invasive aspergillosis among hematopoietic stem cell transplant recipients. Here, we show that PTX3 polymorphisms are independent risk factors for invasive mold infection among 1101 solid organ transplant recipients, thereby strengthening their role in mold infection pathogenesis and patient's risk stratification. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
    Clinical Infectious Diseases 05/2015; 61(4). DOI:10.1093/cid/civ386 · 8.89 Impact Factor
  • Fabian H Weissbach · Hans H Hirsch ·
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    ABSTRACT: Despite availability of protective vaccines, tick-borne encephalitis virus (TBEV) infections have been increasingly reported to the European centres of disease control over the past two decades. Since diagnosis of TBEV exposure relies on serologic testing, we compared two commercial assays, ImmunozymFSME-IgG (ELISA-1) and FSMEVienna-IgG Euroimmun (ELISA-2). Both assays use whole TBEV antigens, but differ in viral strains (Neudoerfl for ELISA-1; K23 for ELISA-2), and cut-off definitions. Testing 398 healthy blood donors, ELISA-1 showed higher reactivity than ELISA-2 (p<0.001) suggesting different assay properties. This was supported by Bland-Altman analysis for OD450nm (mean bias +0.32; 95% limits of agreement: -0.31 to +0.95) and persisted after transformation in Vienna units. Concordant results were observed for 276 (69%) sera (44 positive, 232 negative). Discordant results were observed for 122 (31%) sera: 15 fully discordant, all being ELISA-1 positive/ELISA-2 negative; 107 partially discordant sera (101 sera being ELISA-1 indeterminate/ELISA-2 negative; 6 having positive or indeterminate reactivity in both ELISAs). Neutralization at 1:10 dilution tested positive in 33 of 44 concordant positive sera; in 1 of 15 fully discordant sera; and 1 of 33 partially discordant sera. Indirect immunofluorescence revealed high antibody titres of ≥100 for yellow fever virus in 18 cases, and dengue virus in one case suggesting that cross-reactivity contributed to ELISA-1 results. We conclude that 1. cross-reactivity among flaviviruses remains a limitation of TBEV serology; 2. ELISA-2 revealed reasonable sensitivity and specificity for anti-TBEV IgG population screening of human sera; 3. neutralization testing is most specific, and should be reserved for selective questions. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
    Clinical and vaccine Immunology: CVI 04/2015; DOI:10.1128/CVI.00096-15 · 2.47 Impact Factor
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    ABSTRACT: Demonstration of survival and outcome of progressive multifocal leukoencephalopathy (PML) in a 56-year-old patient with common variable immunodeficiency, consisting of severe hypogammaglobulinemia and CD4+ T lymphocytopenia, during continuous treatment with mirtazapine (30 mg/day) and mefloquine (250 mg/week) over 23 months. Regular clinical examinations including Rankin scale and Barthel index, nine-hole peg and box and block tests, Berg balance, 10-m walking tests, and Montreal Cognitive Assessment (MoCA) were done. Laboratory diagnostics included complete blood count and JC virus (JCV) concentration in cerebrospinal fluid (CSF). The noncoding control region (NCCR) of JCV, important for neurotropism and neurovirulence, was sequenced. Repetitive MRI investigated the course of brain lesions. JCV was detected in increasing concentrations (peak 2568 copies/ml CSF), and its NCCR was genetically rearranged. Under treatment, the rearrangement changed toward the archetype sequence, and later JCV DNA became undetectable. Total brain lesion volume decreased (8.54 to 3.97 cm(3)) and atrophy increased. Barthel (60 to 100 to 80 points) and Rankin (4 to 2 to 3) scores, gait stability, and box and block (7, 35, 25 pieces) and nine-hole peg (300, 50, 300 s) test performances first improved but subsequently worsened. Cognition and walking speed remained stable. Despite initial rapid deterioration, the patient survived under continuous treatment with mirtazapine and mefloquine even though he belongs to a PML subgroup that is usually fatal within a few months. This course was paralleled by JCV clones with presumably lower replication capability before JCV became undetectable. Neurological deficits were due to PML lesions and progressive brain atrophy.
    Journal of NeuroVirology 04/2015; 21(6). DOI:10.1007/s13365-015-0340-4 · 2.60 Impact Factor
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    ABSTRACT: Background. The hepatitis C virus (HCV) epidemic is evolving rapidly in patients infected with human immunodeficiency virus (HIV). We aimed to describe changes in treatment uptake and outcomes of incident HCV infections before and after 2006, the time-point at which major changes in HCV epidemic became apparent. Methods. We included all adults with an incident HCV infection before June 2012 in the Swiss HIV Cohort Study, a prospective nationwide representative cohort of individuals infected with HIV. We assessed the following outcomes by time period: the proportion of patients starting an HCV therapy, the proportion of treated patients achieving a sustained virological response (SVR), and the proportion of patients with persistent HCV infection during follow-up. Results. Of 193 patients with an HCV seroconversion, 106 were diagnosed before and 87 after January 2006. The proportion of men who have sex with men increased from 24% before to 85% after 2006 (P < .001). Hepatitis C virus treatment uptake increased from 33% before 2006 to 77% after 2006 (P < .001). Treatment was started during early infection in 22% of patients before and 91% after 2006 (P < .001). An SVR was achieved in 78% and 29% (P = .01) of patients treated during early and chronic HCV infection. The probability of having a detectable viral load 5 years after diagnosis was 0.67 (95% confidence interval [CI], 0.58-0.77) in the group diagnosed before 2006 and 0.24 (95% CI, 0.16-0.35) in the other group (P < .001). Conclusions. In recent years, increased uptake and earlier initiation of HCV therapy among patients with incident infections significantly reduced the proportion of patients with replicating HCV.
    03/2015; 2(1):ofv026. DOI:10.1093/ofid/ofv026
  • Garth D Tylden · Hans H Hirsch · Christine Hanssen Rinaldo ·
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    ABSTRACT: BK polyomavirus (BKPyV)-associated hemorrhagic cystitis (PyVHC) complicates 5 - 15% of allogeneic hematopoietic stem cell transplantations. Targeted antivirals are still unavailable. Brincidofovir (BCV, previously CMX001) has shown inhibitory activity against diverse viruses, including BKPyV in a primary renal tubule cell culture model of polyomavirus-associated nephropathy. We investigated the effects of BCV in BKPyV-infected and uninfected primary human urothelial cells (HUCs), the target cells of BKPyV in PyVHC. The BCV concentrations causing 50 and 90% reductions (EC50 and EC90) in the number of intracellular BKPyV genome equivalents per cell (icBKPyV) were 0.27 μM (95%CI 0.24-0.29) and 0.59 μM (95%CI 0.53-0.65) respectively. At 0.63 μM, BCV reduced viral late gene expression by 90% and halted progeny release. Preinfection treatment for only 24 hours reduced icBKPyV similarly to treatment from 2-72 hours postinfection, while combined pre- and postinfection treatment suppressed icBKPyV completely. After investigating BCV's effects on HUC-viability, mean selectivity indices at 50 and 90% inhibition (SI50 and SI90) were calculated for cellular DNA replication at 2.7 and 2.9 respectively, mitochondctivity at 8.9 and 10.4, total ATP at 8.6 and 8.2 and membrane integrity at 25.9 and 16.7. The antiviral and cytostatic effects, but less so the cytotoxic effects, were inversely related to cell density. The cytotoxic effects at concentrations ≥10 μM were rapid and likely related to BCV's lipid moiety. After carefully defining the antiviral, cytostatic, and cytotoxic properties of BCV in HUCs, we conclude that a preemptive or prophylactic approach in PyVHC is likely to give the best results. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
    Antimicrobial Agents and Chemotherapy 03/2015; 59(6). DOI:10.1128/AAC.00238-15 · 4.48 Impact Factor
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    ABSTRACT: The plasmid pBKV (34-2) (ATCC 45025) contains the entire BK polyomavirus Dunlop genome. Sequencing revealed 12 point mutations compared to the GenBank sequence, but only 4 point mutations compared to the published sequence. The origin of these differences is unknown, but may impact virological as well as diagnostic research and development.
    Genome Announcements 03/2015; 3(2):e00046-15. DOI:10.1128/genomeA.00046-15
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    ABSTRACT: Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with ≥3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR ≤ 60 ml/min/1.73 m2. Poisson regression was used to develop a risk score, externally validated on two independent cohorts. In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1:393 chance of developing CKD in the next 5 y in the low risk group (risk score < 0, 33 events), rising to 1:47 and 1:6 in the medium (risk score 0-4, 103 events) and high risk groups (risk score ≥ 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.
    PLoS Medicine 03/2015; 12(3):e1001809. DOI:10.1371/journal.pmed.1001809 · 14.43 Impact Factor
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    Rainer Gosert · Hans H. Hirsch ·

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    ABSTRACT: There is limited clinical evidence on the utility of the monitoring of Epstein Barr virus (EBV) DNAemia in the preemptive management of post-transplant lymphoproliferative disease (PTLD) in solid organ transplant (SOT) recipients. We investigated current preventive measures against EBV-related PTLD through a web-based questionnaire sent to 669 SOT programs in 35 European countries. This study was performed on behalf of the ESGICH study group from the European Society of Clinical Microbiology and Infectious Diseases. A total of 71 SOT programs from 15 European countries participated in the study. EBV serostatus of the recipient is routinely obtained in 69/71 centers (97%) and 64 (90%) have access to EBV DNAemia assays. EBV monitoring is routinely used in 85.9% of the programs, and 77.4% reported performing preemptive treatment for patients with significant EBV DNAemia levels. Preemptive treatment for EBV DNAemia included reduction of immunosuppression in 50.9%, switch to m-TOR inhibitors in 30.9%, and use of rituximab in 14.5% of programs. Imaging by PDG-PET total body is used in 60.9% of centers in order to rule out PTLD and complemented computer tomography in 50%. In 10.9% of centers, PDG-PET is included in the first-line diagnostic work-up in patients with high risk EBV DNAemia. Despite the lack of definitive evidence, EBV load measurements are frequently used in Europe to guide diagnostic work-up and preemptive reduction of immunosuppression. We need prospective and controlled studies to define the impact of EBV monitoring in reducing the risk of PTLD in SOT recipients. Copyright © 2015. Published by Elsevier Ltd.
    Clinical Microbiology and Infection 02/2015; 21(6). DOI:10.1016/j.cmi.2015.02.002 · 5.77 Impact Factor
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    ABSTRACT: Infectious agents, including the BK polyomavirus (BKPyV), have been proposed as important inflammatory pathogens in prostate cancer. Here, we evaluated whether the preoperative antibody response to BKPyV large T antigen (LTag) and viral capsid protein 1 (VP1) was associated with the risk of biochemical recurrence in 226 patients undergoing radical prostatectomy for primary prostate cancer. Essentially, the multivariate Cox regression analysis revealed that preoperative seropositivity to BKPyV LTag significantly reduced the risk of biochemical recurrence, independently of established predictors of biochemical recurrence such as tumor stage, Gleason score and surgical margin status. The predictive accuracy of the regression model was denotatively increased by the inclusion of the BKPyV LTag serostatus. In contrast, the VP1 serostatus was of no prognostic value. Finally, the BKPyV LTag serostatus was associated with a peculiar cytokine gene expression profile upon assessment of the cellular immune response elicited by LTag. Taken together, our findings suggest that the BKPyV LTag serology may serve as a prognostic factor in prostate cancer. If validated in additional studies, this biomarker may allow for better treatment decisions after radical prostatectomy. Finally, the favorable outcome of LTag seropositive patients may provide a potential opportunity for novel therapeutic approaches targeting a viral antigen.
    Oncotarget 01/2015; 6(8):6459-6469. DOI:10.5167/uzh-109968 · 6.36 Impact Factor
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    ABSTRACT: Unlabelled: In kidney transplant patients with BK polyomavirus (BKPyV) nephropathy, viral variants arise bearing rearranged noncoding control regions (rr-NCCRs) that increase viral early gene expression, replicative fitness, and cytopathology. rr-NCCRs result from various deletions and duplications of archetype NCCR (ww-NCCR) sequences, which alter transcription factor binding sites (TFBS). However, the role of specific TFBS is unclear. We inactivated 28 TFBS in the archetype NCCR by selective point mutations and examined viral gene expression in bidirectional reporter constructs. Compared to the archetype, group 1 mutations increased viral early gene expression similar to rr-NCCR and resulted from inactivating one Sp1 or one Ets1 TFBS near the late transcription start site (TSS). Group 2 mutations conferred intermediate early gene activation and affected NF1, YY1, and p53 sites between early and late TSS. Group 3 mutations decreased early and late gene expression and included two other Sp1 sites near the early TSS. Recombinant viruses bearing group 1 NCCRs showed increased replication in human renal epithelial cells similar to clinical rr-NCCR variants. Group 2 and 3 viruses showed intermediate or no replication, respectively. A literature search revealed unnoticed group 1 mutations in BKPyV nephropathy, hemorrhagic cystitis, and disseminated disease. Importance: The NCCRs of polyomaviruses mediate silent persistence of the viral genome as well as the appropriately timed (re)activation of the viral life cycle. This study indicates that the basal BKPyV NCCR is critically controlled by a hierarchy of single TFBS in the archetype NCCR that direct, modulate, and execute the bidirectional early and late viral gene expression. The results provide new insights into how BKPyV NCCR functions as a viral sensor of host cell signals and shed new light on how transcription factors like Sp1 control bidirectional viral gene expression and contribute to replication and pathology.
    Journal of Virology 01/2015; 89(6). DOI:10.1128/JVI.03625-14 · 4.44 Impact Factor
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    ABSTRACT: Patients undergoing haematopoietic stem cell transplantation (HSCT) are at high risk of severe gastrointestinal bleeding caused by infections, graft versus host disease, and disturbances in haemostasis. BK polyomavirus (BKPyV) is known to cause hemorrhagic cystitis, but there is also evidence of BKV shedding in stool and its association with gastrointestinal disease. We report putative association of BKPyV replication with high plasma viral loads in a pediatric HSCT patient developing hemorrhagic cystitis and severe gastrointestinal bleeding necessitating intensive care. The observation was based on chart review and analysis of BKPyV DNA loads in plasma and urine as well as retrospective BKPyV-specific IgM and IgG measurements in weekly samples until three months post-transplant. The gastrointestinal bleeding was observed after a >100-fold increase in the plasma BKPyV loads and the start of hemorrhagic cystitis. The BKPyV-specific antibody response indicated past infection prior to transplantion, but increasing IgG titers were seen following BKPyV replication. The gastrointestinal biopsies were taken at a late stage of the episode and were no longer informative of BK polyomavirus involvement. In conclusion, gastrointestinal complications with bleeding are a significant problem after allogeneic HSCT to which viral infections including BKPyV may contribute.
    Journal of Clinical Virology 11/2014; 62. DOI:10.1016/j.jcv.2014.11.016 · 3.02 Impact Factor
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    ABSTRACT: BACKGROUND Single-nucleotide polymorphisms (SNPs) in immune genes have been associated with susceptibility to invasive mold infection (IMI) among hematopoietic stem cell but not solid-organ transplant (SOT) recipients. METHODS Twenty-four SNPs from systematically selected genes were genotyped among 1101 SOT recipients (715 kidney transplant recipients, 190 liver transplant recipients, 102 lung transplant recipients, 79 heart transplant recipients, and 15 recipients of other transplants) from the Swiss Transplant Cohort Study. Association between SNPs and the end point were assessed by log-rank test and Cox regression models. Cytokine production upon Aspergillus stimulation was measured by enzyme-linked immunosorbent assay in peripheral blood mononuclear cells (PBMCs) from healthy volunteers and correlated with relevant genotypes. RESULTS Mold colonization (n = 45) and proven/probable IMI (n = 26) were associated with polymorphisms in the genes encoding interleukin 1β (IL1B; rs16944; recessive mode, P = .001 for colonization and P = .00005 for IMI, by the log-rank test), interleukin 1 receptor antagonist (IL1RN; rs419598; P = .01 and P = .02, respectively), and β-defensin 1 (DEFB1; rs1800972; P = .001 and P = .0002, respectively). The associations with IL1B and DEFB1 remained significant in a multivariate regression model (P = .002 for IL1B rs16944; P = .01 for DEFB1 rs1800972). The presence of 2 copies of the rare allele of rs16944 or rs419598 was associated with reduced Aspergillus-induced interleukin 1β and tumor necrosis factor α secretion by PBMCs. CONCLUSIONS Functional polymorphisms in IL1B and DEFB1 influence susceptibility to mold infection in SOT recipients. This observation may contribute to individual risk stratification.
    The Journal of Infectious Diseases 11/2014; 211(10). DOI:10.1093/infdis/jiu636 · 6.00 Impact Factor
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    ABSTRACT: In simian virus 40 (SV40) and several other polyomaviruses, the TATA box of the early promoter is embedded in an AT tract that is also an essential part of the replication origin. We generated an "AT trap", an SV40 genome lacking the AT tract and unable to grow in CV-1 monkey cells. Co-transfection of the AT trap with oligonucleotides containing AT tracts of human polyomaviruses, a poly (A:T) tract, or variants of the SV40 wild type sequence all restored infectious virus. In a transfection of the AT trap without suitable oligonucleotide, an AT-rich segment was incorporated, stemming either from bovine (calf serum) or monkey (host cell) DNA. Similarly, when cells were grown with human serum, a human DNA segment was captured by SV40 to substitute for the missing AT stretch. We conclude that the virus is quite opportunistic in accepting heterologous substitutes, and that even low-abundance DNA from serum can be incorporated into the viral genome.
    Journal of General Virology 11/2014; 96(Pt_3). DOI:10.1099/vir.0.071274-0 · 3.18 Impact Factor

Publication Stats

9k Citations
1,401.04 Total Impact Points


  • 2011-2015
    • University of Zurich
      • Institute of Virology
      Zürich, Zurich, Switzerland
  • 2001-2015
    • Universitätsspital Basel
      • Klinik für Infektiologie & Spitalhygiene
      Bâle, Basel-City, Switzerland
  • 1991-2015
    • Universität Basel
      • • Department of Biomedicine
      • • Institut für Medizinische Mikrobiologie
      • • Institute of Geology and Paleontology
      Bâle, Basel-City, Switzerland
  • 2012
    • Justus-Liebig-Universität Gießen
      Gieben, Hesse, Germany
    • Universität des Saarlandes
      • Institut für Virologie
      Saarbrücken, Saarland, Germany
  • 2008-2011
    • University Hospital of North Norway
      • Department of Microbiology and Infection Control
      Tromsø, Troms, Norway
  • 2009-2010
    • National Institutes of Health
      Maryland, United States
  • 2006
    • Kantonsspital St. Gallen
      San Gallo, Saint Gallen, Switzerland
    • Cornell University
      Итак, New York, United States
  • 2003
    • University of Geneva
      • Division of Infectious Diseases
      Carouge, GE, Switzerland
  • 1991-1992
    • Universität Stuttgart
      • Institute of Biochemistry
      Stuttgart, Baden-Württemberg, Germany
  • 1988
    • University of Freiburg
      Freiburg, Baden-Württemberg, Germany