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host and viral traits predict zoonotic spillover from mammals.the majority of human emerging infectious diseases are zoonotic, with viruses that originate in wild mammals of particular concern (for example, hiv, ebola and sars). understanding patterns of viral diversity in wildlife and determinants of successful cross-species transmission, or spillover, are therefore key goals for pandemic surveillance programs. however, few analytical tools exist to identify which host species are likely to harbour the next human virus, or which viruses can cross species ...201728636590
investigation of human jc and bk polyomaviruses in breast carcinomas.we have previously showed the presence of the simian virus 40 (sv40) and the mouse mammary tumor virus (mmtv)-like in a significant proportions of tunisian breast carcinomas. however, to date there are no published studies concerning evaluation of the possible implication of the human polyomaviruses jc (jcv) and bk (bkv) in breast carcinomas. the presence of jcv and bkv dna was investigated by pcr in a 123 primary breast carcinomas and matched adjacent non-tumor breast tissues. the results were ...201122108781
high prevalence of bk polyomavirus sequences in human papillomavirus-16-positive precancerous cervical lesions.high- and low-grade cervical lesions were analyzed for the presence of polyomavirus (pyv) and human papillomavirus (hpv) sequences. in precancerous cervical lesions, the overall prevalence of pyv sequences was 44% (41/93). specifically, among the pyv-positive samples, 83% (34/41) tested positive for bk polyomavirus (bkv) sequences, whereas 17% (7/41) were positive for jc-virus. none of the samples were positive for simian virus 40. the presence of bkv dna in high-grade squamous intraepithelial l ...201121837794
Molecular characterization of BK polyomavirus subtypes in renal transplant recipients in Brazil.BK polyomavirus (BKV) is highly prevalent in the world population. Different reports indicate that BKV subtypes and subgroups present an uneven geographical distribution which might be correlated with human migration. However, there is a lack of data on the BKV subtype distribution in the South American population. The occurrence of BKV subtypes and subgroups detected in 51 kidney transplant recipients in Rio de Janeiro, Brazil is described. According to genetic studies, the population in this r ...201121678444
analysis of dna methylation in human bk virus.human bk virus may cause nephropathy due to viral replication in patients who have undergone renal transplantation. however, the mechanism regulating replication of bkv is still not clear. previous studies have suggested that epigenetic modifications may play a crucial role in virus replication. in this study, the dna methylation profiles of five cpg sites located within the promoter/enhancer regions and nine cpg sites located within the early and late coding regions of the replicating bkv genom ...201121626299
inhibition of respiratory syncytial virus in vitro and in vivo by the immunosuppressive agent leflunomide.respiratory syncytial virus (rsv) is the primary cause of bronchiolitis and pneumonia in infants and young children worldwide and is often the cause of infections in bone marrow, solid organ transplant, cystic fibrosis and congenital heart disease patients, as well as respiratory tract disease in elderly adults. treatment options are limited to ribavirin, which is only marginally effective, and passive immunoprophylaxis, which is very expensive. the immunosuppressive agent leflunomide has been s ...201121555813
evaluation of human polyomavirus bk as a potential cause of villitis of unknown etiology and spontaneous abortion.polyomavirus bk (bkv) is a widely latent pathogen in man. although viral reactivation during pregnancy has been demonstrated, and polyomaviruses have been linked to chromosomal abnormalities, a pathogenic role for bkv in fetoplacental disease has not been explored. we performed in situ hybridization studies with bkv probes on cases of villitis of unknown etiology (102), diffuse villitis (25), and spontaneous abortion (22). we found no evidence that bkv plays a role in the pathogenesis of these c ...201121503916
reversible ureteral obstruction due to polyomavirus infection after percutaneous nephrostomy catheter placement.bk virus (bkv) is a human polyomavirus that remains latent in the urinary tract epithelium in most individuals. however, in immunocompromised states, including after hematopoietic stem cell transplantation (hsct), bkv may reactivate and cause infection predominantly affecting the bladder, commonly manifested as hemorrhagic cystitis. renal insufficiency, occasionally requiring hemodialysis, is not uncommon and was previously attributed to medications or the development of tubulointestitial nephri ...201121396475
an identical mirna of the human jc and bk polyoma viruses targets the stress-induced ligand ulbp3 to escape immune elimination.the human polyoma viruses jcv and bkv establish asymptomatic persistent infection in 65%-90% of humans but can cause severe illness under immunosuppressive conditions. the mechanisms by which these viruses evade immune recognition are unknown. here we show that a viral mirna identical in sequence between jcv and bkv targets the stress-induced ligand ulbp3, which is a protein recognized by the killer receptor nkg2d. consequently, viral mirna-mediated ulbp3 downregulation results in reduced nkg2d- ...201121320692
functional reorganization of promyelocytic leukemia nuclear bodies during bk virus infection.bk virus (bkv) is the causative agent for polyomavirus-associated nephropathy, a severe disease found in renal transplant patients due to reactivation of a persistent bkv infection. bkv replication relies on the interactions of bkv with many nuclear components, and subnuclear structures such as promyelocytic leukemia nuclear bodies (pml-nbs) are known to play regulatory roles during a number of dna virus infections. in this study, we investigated the relationship between pml-nbs and bkv during i ...201121304169
clinical aspects of intravenous immunoglobulin use in solid organ transplant recipients.intravenous immunoglobulin products (ivig) are derived from pooled human plasma from thousands of donors and have been used for the treatment of primary immunodeficiency disorders for nearly 30 years. ivig products are also effective in the treatment of autoimmune and inflammatory disorders, however the precise mechanism(s) of immune modulation are unknown. recent data suggests that ivig has a much broader ability to regulate cellular immunity, including innate and adaptive components. ivig is a ...201121219579
prevalence of polyomaviruses bk, jc, sv40, ki, and wu in non-malignant tonsil specimens.the recently described polyomaviruses ki and wu have been detected in respiratory samples, stools, tonsils, and blood, particularly in immunocompromised conditions, although little is known about tissue tropism. herein we investigated the occurrence of kiv and wuv in non-malignant tonsillar specimens by real-time quantitative pcr; the presence of polyomaviruses bk, jc and sv40-dna was also evaluated.201021196897
viral drug sensitivity testing using quantitative pcr: effect of tyrosine kinase inhibitors on polyomavirus bk replication.our objective was to determine whether quantitative polymerase chain reaction (pcr) can be used to measure the effect of tyrosine kinase (tk) inhibition on polyomavirus bk (bkv) replication. the bkv was grown in a cell culture system. the rate of viral replication in the presence or absence of the drug being tested was assessed by amplifying the viral genome using primers directed against the viral capsid 1 protein. dasatinib, erlotinib, gefitinib, imatinib, sunitinib, and sorafenib all showed a ...201021088155
in-gel technology for pcr genotyping and pathogen detection.this work describes the use of polyacrylamide gel and pcr reagents photopolymerized in a mold to create an array of semisolid posts that serve as reaction vessels for parallel pcr amplification of an externally added template. dna amplification occurred in a cylindrical, self-standing 9 × 9 array of gel posts each less than 1 μl in volume. photopolymerization of the gel with an intercalating dye added prior to polymerization permitted acquisition of real-time pcr data and melting curve analysis ...201020809605
emerging viruses in transplantation.several viruses have recently gained importance for the transplant recipient. the purpose of this review is to give an update on emerging viruses in transplantation.201020592533
polyomavirus bk neutralizing activity in human immunoglobulin preparations.polyomavirus bk (bkv) infection can cause nephropathy in the allograft kidney. no well-established drug treatment is available at this time. human intravenous immunoglobulins (ivig) have been used as an empiric therapy without proof of effectiveness.201020568674
evaluation of low-dose rituximab induction therapy in living related kidney transplantation.rrituximab has been used for desensitization of anti-blood type antibody and anti-human leukocyte antigen (hla) antibody as an induction immunosuppressant in our hospital. after having used rituximab for more than 2 years, we performed a retrospective study to clarify the effectiveness and safety of rituximab.201020559108
meaning of early polyomavirus-bk replication post kidney transplant.polyomavirus bk (bkv) infection is ubiquitous in the human population. under immunosuppression, bkv can undergo reactivation resulting in viral replication. what really happens in the early hours posttransplantation is not clearly defined; the meaning of early viremia and viruria is not clear. bkv viremia is considered a marker of infection. the aim of our study was to investigate the prevalence of early bkv infection in kidney transplant patients, to evaluate the relationship to infections at 3 ...201020534245
update on human polyomaviruses and cancer.over 50 years of polyomavirus research has produced a wealth of insights into not only general biologic processes in mammalian cells, but also, how conditions can be altered and signaling systems tweaked to produce transformation phenotypes. in the past few years three new members (kiv, wuv, and mcv) have joined two previously known (jcv and bkv) human polyomaviruses. in this review, we present updated information on general virologic features of these polyomaviruses in their natural host, conce ...201020399955
host-specific replication of bk virus dna in mouse cell extracts is independently controlled by dna polymerase alpha-primase and inhibitory activities.the activation of the human polyomavirus bk causes polyomavirus-associated nephropathy in immunocompromised humans. studies of the virus have been restricted since the virus dna replication is species specific. cell-based and cell-free dna replication systems, including the bk virus (bkv) monopolymerase dna replication system using purified proteins, reproduce the species specificity (28). therefore, the major host proteins comprising this assay, dna polymerase alpha-primase (pol-prim) and repli ...201020392840
prevalence and stability of antibodies to the bk and jc polyomaviruses: a long-term longitudinal study of australians.serology has been used to indicate past infection by the human polyomaviruses bk virus (bkv) and jc virus (jcv), because the site of primary infection is not established fully. little is known about bkv and jcv antibody stability over time. we investigated bkv and jcv seroprevalence and antibody stability over time in an australian population-based study. serum was collected from 458 adults participating in a longitudinal skin cancer study in queensland in 1992, 1993 and 1996, and 117 people had ...201020219899
generation of merkel cell polyomavirus (mcv)-like particles and their application to detection of mcv antibodies.the genome of a new human polyomavirus, known as merkel cell polyomavirus (mcv), has recently been reported to be integrated within the cellular dna of merkel cell carcinoma (mcc), a rare human skin cancer. to investigate mcv seroprevalence in the general population, we expressed three different mcv vp1 in insect cells using recombinant baculoviruses. viruslike particles (vlps) were obtained with only one of the three vp1 genes. high-titer antibodies against vp1 vlps were detected in mice immuni ...201020181914
structural evaluation of new human polyomaviruses provides clues to pathobiology.in the past three years, remarkable discoveries have added three new human polyomaviruses (ki virus (kiv), wu virus (wuv) and merkel cell virus (mcv)) to a class that previously had only two disease-causing members (bk virus (bkv) and jc virus (jcv)) identified. two monkey polyomaviruses, simian virus (sv)40 and b-cell lymphotropic polyomavirus (lpv) are also present in humans. kiv and wuv lack the agnoprotein coding sequence and regulatory micro (mi)rna clusters of bkv, jcv and sv40. mcv lacks ...201020176487
a suppressive effect of cyclosporine a on replication and noncoding control region activation of polyomavirus bk virus.the effect of cyclosporine a (csa) on polyomavirus bk virus (bkv) replication remains unclear. the aim of this in vitro study was to investigate the effect of csa on bkv replication in human uroepithelial cells.201020145520
human polyoma viruses and disease with emphasis on clinical bk and jc.polyoma viruses are ubiquitous infecting many different mammalian species including humans. there are five known human polyoma viruses. jc virus and bk virus are two polyoma viruses identified nearly three decades ago. recently wu, ki and merkel cell polyoma viruses have been isolated from humans. the exact role of these three newly discovered viruses in human disease is not known. most human polyoma disease is caused by bk and jc viruses which are usually acquired in childhood. approximately 50 ...201020060360
multiplex real-time pcr assay for simultaneous quantification of bk polyomavirus, jc polyomavirus, and adenovirus dna.in recent years, virus-induced nephropathy caused mainly by bk polyomavirus (bkpyv), jc polyomavirus (jcpyv), and adenovirus has emerged as a problem in renal transplant patients. in the present study, we developed a multiplex real-time pcr assay to quantify the viral load of bkpyv, jcpyv, and adenovirus simultaneously. the dynamic range covered at least 6 orders of magnitude. this system was specific and reproducible, even in the presence of large amounts of dna of other viruses. to validate th ...201020053854
lymphotropic polyomavirus is detected in peripheral blood from immunocompromised and healthy subjects.lymphotropic polyomavirus (lpv) was isolated from a b-lymphoblastoid cell line of an african green monkey. this virus shares some characteristics with human polyomaviruses, but it is antigenically distinct from bk virus (bkv) and jc virus (jcv). seroepidemiological studies revealed that human sera react in the presence of lpv antigens, and, recently, the viral genome was amplified in the peripheral blood from patients affected with hiv-related leukoencephalopathies.201020042367
do human polyoma viruses and human immunodeficiency virus share common co-receptors?host and/or viral factors involved in human polyomavirus (hpov) infection in persons living with hiv remain unknown. a hypothesis is outlined suggesting the importance of the co-receptors ccr5, ccr2, and cxcr4 not only for hiv, but also for hpov. functionally capable receptors coded by wild-type (wt) genotypes could facilitate internalization of hpov in the cell resulting in brain and/or kidney infection/s in hiv infected individuals. forty-nine bulgarians with hiv, all treated by haart, without ...201019950235
[evaluation of the lightcycler 480 real-time pcr system for the measurement of cmv, ebv, hhv-6 and bkv viral loads in whole blood].the roche lightcycler 480 (lc480) system was evaluated for quantitative molecular diagnosis of opportunistic viral infections caused by human cytomegalovirus (cmv), epstein-barr virus (ebv), human herpesvirus 6 (hhv-6), and bk virus (bkv), in comparison with "in-house" real-time pcr assays.201019892483
detection of viral dna in kidney graft preservation and washing solutions is predictive of posttransplant infections in pediatric recipients.in pediatric kidney transplant recipients, viral infections occur soon after transplant and may be transmitted from the graft.200919803803
regulation of gene expression in primate polyomaviruses.polyomaviruses are a growing family of small dna viruses with a narrow tropism for both the host species and the cell type in which they productively replicate. species host range may be constrained by requirements for precise molecular interactions between the viral t antigen, host replication proteins, including dna polymerase, and the viral origin of replication, which are required for viral dna replication. cell type specificity involves, at least in part, transcription factors that are nece ...200919640999
absence of simian virus 40, bk, and jc polyomavirus dna in squamous cell carcinoma limited to the oral cavity.head and neck squamous cell carcinomas (sccs) are among the most aggressive types of cancer. the simian virus 40 (sv40), which is a polyomavirus known for its oncogenic potential, was found as a contaminant of oral vaccines and has been related to human pleomorphic adenoma in the parotid gland. the aim of this study was to evaluate the presence of sv40 and 2 human polyomaviruses-bk virus (bkv) and jc virus (jcv)-in a large sample of sccs of the oral cavity.201019626633
update on human polyomavirus bk nephropathy.polyomavirus bk (bkv) has ebeen identified as the main cause of polyomavirus-associated nephropathy, a major cause of renal allograft failure. although bkv-associated nephropathy develops in only 2% to 5% of renal transplant recipients, its prognosis when present is very poor, with irreversible graft failure developing in 45% of affected patients. while the use of urine cytology for the detection of decoy cells has been in use for decades, other diagnostic modalities to detect bkv have emerged, ...200919626630
[focal segmental glomerulosclerosis related to bk virus in a child with nephrotic syndrome. a case report].focal segmental glomerulosclerosis (fsgs) is observed in about 10 % of children with idiopathic nephrotic syndrome; this disorder is usually resistant to corticoid therapy. in the last few years, five histological types of fsgs have been recognized; the collapsing nephropathy type is characterized by a rapid evolution to chronic renal failure.200919624974
detection of bk, jc, wu, or ki polyomaviruses in faecal, urine, blood, cerebrospinal fluid and respiratory samples.the recently described wu (wuv) and ki (kiv) polyomaviruses have been primarily detected in respiratory samples, however other body sites have not been extensively investigated to date. the related human polyomaviruses jcv and bkv in contrast, have been detected in a wide range of sample types, leading to increased knowledge about their biology and pathogenesis.200919515607
jc virus: an oncogenic virus in animals and humans?jc virus (jcv) is a human polyomavirus of the polyomaviridae family, which also includes bk virus and simian vacuolating virus 40 (sv40). jc virus was first isolated in 1971 from the brain of a patient with progressive multifocal leukoencephalopathy (pml). like other polyomaviruses, jcv has a restricted host range. the virus infects the majority of the human population with seroconversion occurring during adolescence. jcv has a limited and specific tissue tropism infecting the kidney and oligode ...200919505654
mycophenolate mofetil: effects on cellular immune subsets, infectious complications, and antimicrobial activity.mycophenolate mofetil (mmf) is one of the most frequently used immunosuppressive drugs in solid organ transplant recipients. mmf is an inhibitor of inosine-5'-monophosphate, and is able to preferentially inhibit b-cell and t-cell function. the immunosuppressive abilities of mmf have made it one of the most successful anti-rejection drugs in transplant patients, but patients also appear to have increased susceptibility to infections, specifically cytomegalovirus and bk virus. despite its associat ...200919497072
comparison of the distribution patterns of bk polyomavirus lineages among china, korea and japan: implications for human migrations in northeast asia.bkv is widespread among humans, infecting children asymptomatically and then persisting in renal tissue. based on the serological or phylogenetic method, bkv isolates worldwide are classified into four subtypes (i-iv), with subtypes i and iv further divided into several genetically-distinct subgroups. since, similarly to jcv, a close relationship exists between bkv lineages and human populations, bkv should be useful as a marker to trace human migrations. to elucidate ancient human migrations in ...200919457167
restriction of human polyomavirus bk virus dna replication in murine cells and extracts.bk virus (bkv) causes persistent and asymptomatic infections in most humans and is the etiologic agent of polyomavirus-associated nephropathy (pvan) and other pathologies. unfortunately, there are no animal models with which to study activation of bkv replication in the human kidney and the accompanying pvan. here we report studies of the restriction of bkv replication in murine cells and extracts and the cause(s) of this restriction. upon infection of murine cells, bkv expressed large t antigen ...200919297467
high frequency and diversity of rearrangements in polyomavirus bk noncoding regulatory regions cloned from urine and plasma of israeli renal transplant patients and evidence for a new genetic subtype.polyomavirus bk (bkv) establishes latent infection in various human tissues, including the kidney. reactivation following renal transplantation (rt) may cause bkv-associated nephropathy, leading to graft loss. bkv reactivation is often associated with extensive rearrangements in the bkv noncoding regulatory region (ncrr). we explored the formation and predominance of the rearrangements versus the diversity of the rearrangements by cloning and characterizing pcr-amplified ncrr sequences from six ...200919261800
identification of species-specific and cross-reactive epitopes in human polyomavirus capsids using monoclonal antibodies.the human antibody response to polyomavirus capsid proteins is not well characterized. recombinant bk virus (bkv), jc virus (jcv) and simian virus 40 (sv40) virus-like particles (vlp) were produced in a baculovirus system, and mouse monoclonal antibodies (mabs) to these proteins were generated using standard methods. nine of 12 bkv mabs showed neutralizing activity. the non-neutralizing antibodies also bound bkv pseudocapsids in an elisa binding assay. most antibodies recognized conformational s ...200919218208
bk virus nephropathy after allogeneic stem cell transplantation: a case report and literature review.polyomaviruses are increasingly recognized as important human pathogens. among those, bk virus has been identified as the main cause of polyomavirus-associated nephropathy (pvan), a major cause of renal allograft failure. pvan has also been well described in the setting of non-renal solid organ transplantation. the reports of pvan after hematopoietic stem cell transplantation (hct) are surprisingly very few. here, we describe a patient with treatment-related myelodysplastic syndrome who received ...200919208419
identification of the novel ki polyomavirus in paranasal and lung tissues.ki is a novel polyomavirus identified in the respiratory secretions of children with acute respiratory symptoms. whether this reflects a causal role of the virus in the human respiratory disease remains to be established. to investigate the presence of kiv in the respiratory tissue, we examined 20 fresh lung cancer specimens and surrounding normal tissue along with one paranasal and one lung biopsy from two transplanted children. kiv-vp1 gene was detected in 9/20 lung cancer patients and 2/2 tra ...200919152420
distribution patterns of bk polyomavirus (bkv) subtypes and subgroups in american, european and asian populations suggest co-migration of bkv and the human race.bk polyomavirus (bkv) is ubiquitous in the human population, infecting children asymptomatically and then persisting in the kidney. based on serological and genotyping methods, bkv isolates worldwide are classified into four subtypes (i-iv), with subtype i prevalent throughout the world, subtype iv prevalent in asia and part of europe, and subtypes ii and iii rare throughout the world. phylogenetic analyses of complete genome sequences have identified several geographically distinct subgroups of ...200919088283
geographical identification of cadavers by human parasites.increasing numbers of unidentified cadavers have recently become an important forensic problem in many countries. to identify such cadavers, dna typing method is widely used. however, as this technique requires reference dna samples, a method that would quickly narrow down possible candidates for the cadavers is needed to enable rapid identification. unfortunately, no really reliable methods suitable for this purpose have been available; however, methods using the human parasites, jc virus, bk v ...200819083803
the impact of intercurrent ebv infection on atp levels in cd4+ t cells of pediatric kidney transplant recipients.immuknow measures atp (ng/ml) in pha-activated cd4+ t cells from patient's whole blood. according to published reports, median immuknow is 258 ng/ml in stable pediatric kidney transplant (pkt) recipients > or =12 yr, and 165 ng/ml in those <12 yr. however, data on the effect of infection or ar on immuknow are scarce. we studied the effect of epstein-barr virus (ebv) viremia on immuknow in pkt with gd. twenty-eight pkt with gd were reviewed. group 1 has 19 pkt > or =12 yr, and group 2 has nine pk ...200919017293
infection: is it a cause of bladder cancer?this article reviews the literature regarding the possible correlation between infection and occurrence of bladder cancer. the pubmed literature database was searched from inception to january 2008. keywords of bladder, cancer, parasitic, bacterial, viral and infection, were used. forty studies were included in the review. several investigators support the idea that schistosomiasis is aetiologically related to the development of bladder cancer in individuals infected with schistosoma haematobium ...200818815920
human alpha-defensins inhibit bk virus infection by aggregating virions and blocking binding to host cells.bk virus (bkv) is a polyomavirus that establishes a lifelong persistence in most humans and is a major impediment to success of kidney grafts. the function of the innate immune system in bkv infection and pathology has not been investigated. here we examine the role of antimicrobial defensins in bkv infection of vero cells. our data show that alpha-defensin human neutrophil protein 1 (hnp1) and human alpha-defensin 5 (hd5) inhibit bkv infection by targeting an early event in the viral lifecycle. ...200818782756
epidemiology of bk virus in renal allograft recipients: independent risk factors for bk virus replication.identification of risk factors for bk virus (bkv) replication may improve transplant outcome. we investigated the impact of immunosuppressive drugs on the prevalence of bkv replication in recipients of human renal allografts.200818724220
bkv reactivation in renal transplant recipients: diagnostic and therapeutic strategy--case reports.the polyomaviridae family includes several viruses that are ubiquitous with specific host spectra. the human polyoma viruses bk and jc were discovered in 1971. following primary infection, transmitted by the respiratory and probably the oral route, bk remains latent in uroepithelial cells, in b lymphocytes, or in other tissues (spleen, brain). reactivation with asymptomatic viruria may occur in both immunocompetent subjects and immunocompromised patients. in renal transplant recipients, bkv repl ...200818675128
internally controlled triplex quantitative pcr assay for human polyomaviruses jc and bk.we have developed a triplex taqman-based quantitative pcr assay for the human polyomaviruses jc (jcpyv) and bk (bkpyv). the assay simultaneously detects and quantifies both jcpyv and bkpyv in human clinical samples, and it includes an internal amplification control consisting of murine polyomavirus (mupyv) plasmid dna. we developed the assay for the roche lightcycler 480 platform with the reporter dyes vic, 6-fam, and cy5 for mupyv, bkpyv, and jcpyv, respectively. the assay had a high specificit ...200818614652
evolution of four bk virus subtypes.bk viruses (bkv) comprise four subtypes that are distinguishable by serological and molecular methods with the latter indicating up to four subgroups within subtype i. in this study, the phylogeny of all bkv subtypes was analyzed. phylogenetic analyses of the viral structural protein vp1, concatenated sequences including the t-ag, t-ag, vp1 and vp2 genes and the entire coding region of bkv, each employing several tree inference methods, consistently revealed seven strongly supported clades that ...200818582602
comparison of automated nucleic acid extraction methods with manual extraction.automated nucleic acid extractors can improve workflow and decrease variability in the clinical laboratory. we evaluated qiagen ez1 (valencia, ca) and biomérieux (durham, nc) easymag extractors compared with qiagen manual extraction using targets and matrices commonly available in the clinical laboratory. pooled samples were spiked with various organisms, serially diluted, and extracted in duplicate. the organisms/matrices were bordetella pertussis/bronchoalveolar lavage, herpes simplex virus ii ...200818556770
sv40 large t antigen-specific human t cell memory responses.the continued presence of simian virus 40 (sv40), a monkey polyomavirus, in man is confirmed by the regular detection of sv40-specific antibodies in 5-10% of children who are unlikely to have received contaminated polio-vaccines. the aim of our experiments was to find cellular immunological evidence of sv40 infection in humans by testing memory t cell responses to sv40 large t antigen (tag). as there is some indication that the virus may be present in malignant pleural mesothelioma (mpm) cells, ...200818551603
assessing the value of ureteral stent placement in pediatric kidney transplant recipients.ureteral stent placement at kidney transplantation may reduce stenosis or leakage (s/l) complication rates. however, stent placement may also increase risk for early urinary tract infection (early uti; <3 months after transplant) and bk virus allograft nephropathy (bkvan). in children, the usefulness of stent placement is not well defined.200818408579
an sv40 vp1-derived epitope recognized by cd8+ t cells is naturally processed and presented by hla-a*0201 and cross-reactive with human polyomavirus determinants.the cd8+ t cell responses directed toward the vp1 antigens of human polyomaviruses jc and bk recently were shown to be cross-reactive. two hla-a0201-restricted determinants from each virus have been defined and include jcp100-108 (ilmweavtl) and bkp108-116 (llmweavtv) as well as jcp36-44 (sitevecfl) and bkp44-52 (aitevecfl). we asked whether vp1 from the related sv40 contains similar hla-a0201-restricted determinants. in this study, we demonstrate that cd8+ t cells specific for sv40 vp1 p110-118 ...200818402997
polyomavirus in renal transplantation: a hot problem.polyomavirus bk has emerged as an important complication after kidney transplantation. although, bk nephropathy develops in only 1% to 5% of renal transplant recipients, its prognosis when present is very poor. the most accepted risk factor is the level of immunosuppressive treatment, but the serostatus of donor and recipient and the absence of human leukocyte antigen c7 in donor and/or recipient influence the bk virus (bkv) reactivation. the gold standard in diagnosing bkv nephropathy (bkvn) co ...200818401263
human polyomavirus bk in patients with lupus nephritis: clinical and histological correlations.polyomavirus bk (bkv) reactivation can occur in immunodeficient patients. few studies on bkv infection in patients with systemic lupus erytematosus (sle) nephritis are available. aim of this study was to analyse the prevalence of bkv infection by quantifying viral load and to investigate the association with clinical and histological parameters indicating duration, type and activity of sle.bkv-dna was evaluated by polymerase chain reaction in serum (sbkv) and urine (ubkv) specimens from 40 patie ...200717971361
cytomegalovirus and polyomavirus bk posttransplant.virus replication and progression to disease in transplant patients is determined by patient-, graft- and virus-specific factors. this complex interaction is modulated by the net state of immunosuppression and its impact on virus-specific cellular immunity. due to the increasing potency of immunosuppressive regimens, graft rejections have decreased, but susceptibility to infections has increased. therefore, cytomegalovirus (cmv) remains the most important viral pathogen posttransplant despite av ...200717890268
quantitative real-time polymerase chain reaction for evaluating dnaemia due to cytomegalovirus, epstein-barr virus, and bk virus in solid-organ transplant recipients.testing for cytomegalovirus-, epstein-barr virus-, and bk virus-specific gene targets in specimens from solid-organ transplant recipients for dna by quantitative real-time polymerase chain reaction has been implemented in many diagnostic facilities. this technology provides rapid, accurate, and reproducible results for early detection, monitoring, and medical management of patients with these infections. because these assays are becoming commonly used in clinical practice, the technical variable ...200717879925
biomarker discovery in infectious diseases using seldi.surface enhanced laser desorption ionization-time of flight is a mass spectrometric-based method that requires a minimal amount of sample for analysis and can be used for high-throughput screening. it has been used to discover serum or tissue protein signatures and biomarkers for infectious diseases in the fields of virology (hepatitis b and c viruses, severe acute respiratory syndrome, hiv-1, human t-cell leukemia virus-1 and bk virus), parasitology (trypanosomiasis) and bacteriology (intra-amn ...200717661674
molecular epidemiology characterization of the urinary excretion of polyomavirus in healthy individuals from portugal--a southern european population.the human polyomaviruses--bkv and jcv--are members of polyomaviridae family and after primary infections they persist as latent infection especially in the kidneys. bkv reactivation is mainly related to urinary tract diseases and jcv reactivation can induce the disease progressive multifocal leukoencephalopathy. the aim of our study was to characterize the excretion of polyomaviruses in urine samples of healthy individuals from a portuguese population. we analyzed 498 dna samples using pcr-rflp, ...200717596822
an asian origin for subtype iv bk virus based on phylogenetic analysis.similarly to other members of the polyomaviridae family, bk virus (bkv) is thought to have co-evolved with its human host. bkv has four subtypes that are distinguishable by immunological reactivity, with two (subtypes i and iv) being most prevalent in human populations. subtype i is the major subtype worldwide, whereas subtype iv is prevalent in east asia and europe but rare in africa. the geographic distribution pattern of subtype iv bkv is in apparent disagreement with the hypothesis that bkv ...200717593419
dual infection with polyomavirus bk and acyclovir-resistant herpes simplex virus successfully treated with cidofovir in a bone marrow transplant recipient.a hematopoietic stem cell transplant recipient developed a mucosal herpes simplex virus-1 (hsv-1) infection while under acyclovir (acv) treatment (hsv was later shown to be resistant to acv). concomitantly, the patient presented a hemorrhagic cystitis (hc) due to polyomavirus bk, for which intravenous cidofovir (cdv) was prescribed. the patient benefited from the broad-spectrum anti-dna virus activity of cdv, and not only the hc resolved without signs of nephrotoxicity but also the hsv-1 lesions ...200717461998
bk virus infection, replication, and diseases in pediatric kidney transplantation.polyomavirus-associated nephropathy is diagnosed in 2-8% of pediatric renal transplants and often precedes renal allograft dysfunction. without intervention, however, significant graft dysfunction is observed in more than 50% of cases, although progressive early graft loss is reported in only three of 32 (9%) of cases. no specific treatment is available, but early decrease in immunosuppression is followed by declining human polyomavirus type 1 (bk virus) replication and improved outcome. the dat ...200717377822
bk virus genotype distribution offers information of tracing the geographical origins of unidentified cadaver.there are no efficient methods to determine the geographic origin of unidentified cadavers. we showed earlier that the geographical distribution of the jc virus genotype detected from human kidneys indicates the host's geographical origin. as there are still cadavers from which we cannot detect the jc virus (jcv), we investigated whether the genotype of another virus species belonging to the same family, human bk virus (bkv), could also be used to detect human geographical origin. bkv was found ...200717324543
frequency and phenotype of jc virus-specific cd8+ t lymphocytes in the peripheral blood of patients with progressive multifocal leukoencephalopathy.jc virus (jcv)-specific cd8+ cytotoxic t lymphocytes (ctl) are associated with a favorable outcome in patients with progressive multifocal leukoencephalopathy (pml) and cross-recognize the polyomavirus bk virus (bkv). we sought to determine the frequency and phenotype in fresh blood of cd8+ t cells specific for two a*0201-restricted jcv epitopes, vp1(p36) and vp1(p100), and assess their impact on jc and bk viremia and viruria in 15 healthy subjects, eight human immunodeficiency virus-positive (h ...200717229701
relationships between bk virus lineages and human populations.bk polyomavirus (bkv) is ubiquitous in human populations, infecting children asymptomatically and then persisting in the kidney, in which it can cause nephropathy in renal transplant patients. bkv isolates are classified into four subtypes (i-iv) using serological or genotyping methods, and subtype i is further divided into four subgroups, ia, ib-1, ib-2, and ic, based on dna sequence variations. to clarify whether there is an association between bk virus lineages and human populations, we exami ...200717208484
distribution of human polyomaviruses, adenoviruses, and hepatitis e virus in the environment and in a drinking-water treatment plant.large numbers of viruses are excreted in human feces and urine, which even at low concentrations may cause illness when ingested. some of these viruses have not been traditionally monitored in terms of waterborne diseases and are considered emergent viruses, such as hepatitis e virus (hev) and jc and bk polyomavirus (jcpyv and bkpyv). the high prevalence of human adenoviruses (hadv) and polyomaviruses, which both show dna genomes, in sewage from widely divergent areas has suggested the relevance ...200617180997
sv40 and human cancer: a review of recent data.an unknown proportion of formalin-inactivated poliovirus vaccine lots administered to millions of us residents between 1955 and 1963 was contaminated with small amounts of infectious simian virus 40 (sv40), a polyomavirus of the rhesus macaque. it has been reported that mesothelioma, brain tumors, osteosarcoma and non-hodgkin lymphoma (nhl) contain sv40 dna sequences and that sv40 infection introduced into humans by the vaccine probably contributed to the development of these cancers. the immuni ...200717131333
characterization of highly frequent epitope-specific cd45ra+/ccr7+/- t lymphocyte responses against p53-binding domains of the human polyomavirus bk large tumor antigen in hla-a*0201+ bkv-seropositive donors.human polyomavirus bk (bkv) has been implicated in oncogenic transformation. its ability to replicate is determined by the binding of its large tumor antigen (ltag) to products of tumor-suppressor genes regulating cell cycle, as specifically p53. we investigated cd8+ t immune responses to bkv ltag portions involved in p53 binding in hla-a*0201+ bkv ltag experienced individuals. peptides selected from either p53-binding region (ltag351-450 and ltag533-626) by current algorithms and capacity to bi ...200617096832
use of herpes simplex virus type 1-based amplicon vector for delivery of small interfering rna.silencing of gene expression by small interfering rnas (sirnas) is rapidly becoming a powerful tool for genetic analysis of mammalian cells. the use of dna-based plasmid vectors to achieve transient and stable expression of sirna has been developed to avoid the problems of double-stranded oligonucleotides transfection. these vectors direct the transcription of small hairpin rnas (shrnas) from a polymerase-iii (h1 or u6)-rna gene promoter. however, numerous disadvantages remain, including low tra ...200717051250
t-cell responses to peptide fragments of the bk virus t antigen: implications for cross-reactivity of immune response to jc virus.infection with bk virus (bkv) induces both humoral and cellular immunity, but the viral antigens of t-antigen (t-ag) stimulating t-cell responses are largely unknown. to identify bkv-specific t cells in healthy individuals, peripheral blood lymphocytes were cultured with autologous dendritic cells (dcs) loaded with bkv lysate and t cells were screened for intracellular gamma interferon production after stimulation with an overlapping 15mer peptide library of the bkv t-ag. among many immunogenic ...200616963754
retinoblastoma family proteins as key targets of the small dna virus oncoproteins.rb, the most investigated tumor suppressor gene, is the founder of the rb family of growth/tumor suppressors, which comprises also p107 (rbl1) and rb2/p130 (rbl2). the protein products of these genes, prb, p107 and prb2/p130, respectively, are also known as 'pocket proteins', because they share a 'pocket' domain responsible for most of the functional interactions characterizing the activity of this family of cellular factors. the interest in these genes and proteins springs essentially from thei ...200616936748
evolution of bk virus based on complete genome data.the human polyomavirus bk virus (bkv) is ubiquitous in humans, infecting children asymptomatically. bkv is the only primate polyomavirus that has subtypes (i-iv) distinguishable by immunological reactivity. nucleotide (nt) variations in a major capsid protein (vp1) gene region (designated the epitope region), probably responsible for antigenic diversity, have been used to classify bkv isolates into subtypes. here, with all the protein-encoding gene sequences, we attempted to elucidate the evolut ...200616897259
bk viral reactivation in cardiac transplant patients: evidence for a double-hit hypothesis.bk nephropathy is a significant cause of renal dysfunction in renal allograft recipients. the question of whether bk viral infection plays a role in renal dysfunction in cardiac transplantation patients remains to be answered.200616818124
bk virus infection in kidney transplantation: a case for early intervention.the prognosis for renal allograft survival in a patient with bk virus-associated nephropathy is distressing because nearly 50% of affected grafts are lost. with these statistics in mind, attempting clinical intervention before bk virus disease develops seems appropriate. noninvasive screening tools such as tests to detect decoy cells in urine can enable diagnosis of bk viral infection in its early stages. although it is not entirely clear which patients with bk infection will have bk disease dev ...200616789702
polyomavirus-associated nephropathy: update of clinical management in kidney transplant patients.over the last decade, polyomavirus-associated nephropathy (pvan) has occurred with increasing frequency after renal transplantation, leading to significant renal dysfunction and graft loss. more than 95% of all cases are caused by the human polyomavirus type 1 called the bk virus. the primary treatment for pvan is immunosuppression reduction, which must be carefully balanced against increased risks of rejection. although no validated protocols exist, a first step commonly involves reduction of c ...200616734630
activation of early gene transcription in polyomavirus bk by human immunodeficiency virus type 1 tat.polyomavirus bk (bkv) is a serious problem for immunocompromised patients, where latent virus can enter into the lytic cycle causing cytolytic destruction of host cells. bkv infects >80% of the population worldwide during childhood and then remains in a latent state in the kidney. in the context of immunosuppression in kidney transplant patients, reactivation of the viral early promoter (bkv(e)) results in production of t antigen, enabling virus replication and transition from latency to the lyt ...200616690919
pharmacotherapeutic options for the management of human polyomaviruses.polyomaviruses [bk virus (bkv), jc virus (jcv) and simian virus 40 (sv40)] have been known to be associated with diseases in humans for over thirty years. bkv-associated nephropathy and jcv-induced progressive multifocal leukoencephalopathy (pml) were for many years rare diseases occurring only in patients with underlying severe impaired immunity. over the past decade, the use of more potent immunosuppression (is) in transplantation, and the acquired immune deficiency syndrome (aids) epidemic, h ...200616626040
the pathobiology of polyomavirus infection in man.this article traces the discovery of polyomaviruses and outlines investigations, which shed light on potential modes of transmission of this increasingly important group of human pathogens. the pathobiology of the virus is summarized with particular reference to interactions with host cell receptors, cell entry, cytoplasmic trafficking, and targeting of the viral genome to the nucleus. this is followed by a discussion of sites of viral latency and factors leading to viral reactivation. finally, ...200616626033
a mouse model for polyomavirus-associated nephropathy of kidney transplants.polyomavirus-associated nephropathy is an important cause of dysfunction and failure of renal transplants. bk virus is an ubiquitous human polyoma virus that persistently infects the kidney. this otherwise silent infection can reactivate in immunosuppressed individuals, resulting in renal complications. because polyoma viruses are highly species-specific, we developed a mouse polyoma virus-renal transplant model in order to investigate the pathogenesis of polyomavirus-associated nephropathy. usi ...200616611327
new commercially available pcr and microplate hybridization assay for detection and differentiation of human polyomaviruses jc and bk in cerebrospinal fluid, serum, and urine samples.jc and bk human polyomaviruses (family polyomaviridae) may cause severe neurological or urinary tract pathologies in immunocompromised hosts. in the present study, we evaluated a new commercially available pcr and microplate colorimetric hybridization assay for the standardized differential detection of jc virus (jcv) and bk virus (bkv) genomes in clinical samples. this jc/bk consensus test was first evaluated by testing serial dilutions of jcv or bkv plasmid dna standards and was then compared ...200616597855
the role of sialic acid in human polyomavirus infections.jc virus (jcv) and bk virus (bkv) are human polyomaviruses that infect approximately 85% of the population worldwide [1,2]. jcv is the underlying cause of the fatal demyelinating disease, progressive multifocal leukoencephalopathy (pml), a condition resulting from jcv induced lytic destruction of myelin producing oligodendrocytes in the brain [3]. bkv infection of kidneys in renal transplant recipients results in a gradual loss of graft function known as polyomavirus associated nephropathy (pvn) ...200616575519
human polyomavirus bkv transcriptionally activates dna methyltransferase 1 through the prb/e2f pathway.many dna tumor virus oncogenes are capable of activating and highjacking the host cell's dna replication machinery for its own reproduction purposes through targeting and inactivation of the retinoblastoma pocket protein family. pocket proteins function to regulate cell cycle progression and dna synthesis through inhibitory interactions with the e2f transcription factors. the interaction of viral oncogenes with the pocket proteins is crucial for their transforming activity. we recently demonstra ...200616547506
specific and quantitative detection of human polyomaviruses bkv and jcv by lightcycler real-time pcr.bk virus (bkv) and jc virus (jcv) are the only two known human polyomavirus that typically establish subclinical persistent infections. in immunocompromised hosts reactivation of the jcv infection is the cause of the central nervous system disease progressive multifocal leucoencephalopathy (pml), while bkv may cause renal nephropathy and haemorrhagic cystitis.200616542870
interplay of cellular and humoral immune responses against bk virus in kidney transplant recipients with polyomavirus nephropathy.reactivation of the polyomavirus bk (bkv) causes polyomavirus nephropathy (pvn) in kidney transplant (ktx) recipients and may lead to loss of the renal allograft. we have identified two hla-a*0201-restricted nine-amino-acid cytotoxic t lymphocyte (ctl) epitopes of the bkv major capsid protein vp1, vp1(p44), and vp1(p108). using tetramer staining assays, we showed that these epitopes were recognized by ctls in 8 of 10 (vp1(p44)) and 5 of 10 (vp1(p108)) hla-a*0201+ healthy individuals, while both ...200616537617
the human polyomaviruses.the polyomavirus family includes two members, bk virus (bkv) and jc virus (jcv), that naturally infect humans. these viruses are widely distributed among the population worldwide. primary infection occurs in early childhood and remains for life clinically unapparent in immunocompetent individuals. in the context of severe immunosuppression and other predisposing factors bkv and jcv may reactivate and cause serious illnesses known as polyomavirus-induced nephropathy and progressive multifocal leu ...200616501889
identification of gangliosides gd1b and gt1b as receptors for bk virus.gangliosides have been shown to be plasma membrane receptors for both murine polyomavirus and sv40, while jc virus uses serotonin receptors. in contrast, little is known of the membrane receptor and entry pathway for bk virus (bkv), which can cause severe disease in immunosuppressed bone marrow and renal transplant patients. using sucrose flotation assays, we investigated bkv binding to and interaction with human erythrocyte membranes and determined that this interaction was dependent on a neura ...200616415013
expression analysis and modulation by hiv-tat of the tyrosine phosphatase hd-ptp.the human immunodeficiency virus type 1 tat transactivates viral proteins and also affects the expression of eukaryotic genes. since tat is angiogenic, we assumed that the isolation of differentially expressed genes in tat-treated endothelial cells would yield insights into the molecular mechanisms of the angiogenic process. by rna fingerprinting, we found that tat upregulates the tyrosine phosphatase hd-ptp mrna in a human endothelial cell line. at the moment, little is known about hd-ptp. we h ...200616408268
interstitial cystitis and infectious agents.interstitial cystitis (ic) is a syndrome consisting of severe refractory bladder symptoms of unknown etiology. the disease tends to affect caucasian women with a mean age of 40 years, with 25% of patients under the age of 30. few population based epidemiological studies of ic have been performed. we analyzed a case of interstitial cystitis in a 42-year-old non-smoker woman. in two biopsy samples the presence of viral dna of human polyomavirus bk (bkv), human herpes virus type 1 and type 2 (hhv- ...200516388730
[bk virus infection in a pediatric renal transplant recipient].bk human polyomavirus causes an asymptomatic primary infection in children, then establishing latency mainly in the urinary tratt. viral reactivation can lead to renal pathology in individuals with impaired cellular immune response. this is particularly important in pediatric transplant recipients, who can suffer a primary infection when immunosupressed. we followed up the case of a 5 years old patient who received a renal transplant in october 2003, and presented damaged graft 45 days after the ...200516323666
emerging viral infections after hematopoietic cell transplantation.this overview summarizes recent data on emerging viruses after hematopoietic cell transplantation (hct), including adenovirus, bk virus, human metapneumovirus (hmpv), and human herpesvirus (hhv) 6. the increased recognition of these infections is due to improved molecular detection methods, increased surveillance and more profound immunosuppression in the host. adenovirus can cause serious disease especially in t-cell depleted transplant recipients. adenovirus viremia is an important risk factor ...200516305617
complete nucleotide sequence of polyomavirus sa12.the polyomaviridae have small icosahedral virions that contain a genome of approximately 5,000 bp of circular double-stranded dna. polyomaviruses infect hosts ranging from humans to birds, and some members of this family induce tumors in test animals or in their natural hosts. we report the complete nucleotide sequence of simian agent 12 (sa12), whose natural host is thought to be papio ursinus, the chacma baboon. the 5,230-bp genome has a genetic organization typical of polyomaviruses. sequence ...200516189011
incidence, clinical outcome, and management of virus-induced hemorrhagic cystitis in children and adolescents after allogeneic hematopoietic cell transplantation.we analyzed the incidence, etiology, risk factors, and clinical management of hemorrhagic cystitis (hc) in 102 children who underwent allogeneic stem cell transplantation: 28 from matched siblings, 57 from unrelated donors, and 17 from mismatched relatives. conditioning regimens consisted of high-dose chemotherapy (n=83) or total body irradiation (n=19). in all children, urine and plasma were prospectively screened for human polyomavirus (hpv; bk virus [bkv] and jc virus [jcv]) or adenovirus (ad ...200516182180
distribution, characterization and significance of polyomavirus genomic sequences in tumors of the brain and its covering.the etiology of brain tumors and meningiomas is still unknown. several factors have been considered, such as genetic predisposition and environmental risk factors, but the hypothesis that one or more infectious agents may play a role in tumor pathogenesis has also been investigated. therefore, emphasis was placed on the neurooncogenic family polyomaviridae and the presence of human polyomavirus dna sequences and jcv mrna were examined in malignant human brain biopsies. italian patients affected ...200516173013
fatal bk polyoma viral pneumonia associated with immunosuppression.bk polyoma virus has a worldwide distribution in the human population. primary bk infection takes place during childhood, with the virus remaining latent in many sites. immunosuppressive states can lead to viral reactivation associated with many clinical sequelae. we report a case of fatal bk-related pneumonia in a 69-year-old patient who was immunocompromised because of chemotherapy for chronic lymphocytic leukemia. immunohistochemical, in situ hybridization, and polymerase chain reaction studi ...200516153469
comparative evaluation of three commercial systems for nucleic acid extraction from urine specimens.a nucleic acid extraction system that can handle small numbers of specimens with a short test turnaround time and short hands-on time is desirable for emergent testing. we performed a comparative validation on three systems: the magna pure compact system (compact), the nuclisens minimag extraction instrument (minimag), and the biorobot ez1 system (ez1). a total of 75 urine specimens submitted for polyomavirus bk virus detection were used. the human beta-actin gene was detected on 75 (100%), 75 ( ...200516145151
specific and quantitative detection of human polyomaviruses bkv, jcv, and sv40 by real time pcr.the polyomaviruses that infect humans, bk virus (bkv), jc virus (jcv), and simian virus 40 (sv40), typically establish subclinical persistent infections. however, reactivation of these viruses in immunocompromised hosts is associated with renal nephropathy and hemorrhagic cystitis (hc) caused by bkv and with progressive multifocal leukoencephalopathy (pml) caused by jcv. additionally, sv40 is associated with several types of human cancers including primary brain and bone cancers, mesotheliomas, ...200516087125
prevalence and stability of human serum antibodies to simian virus 40 vp1 virus-like particles.possible human infection with simian virus 40 (sv40) has been of great concern ever since sv40 was discovered in polio vaccines. human populations are sv40-seropositive, but because of serological cross-reactivity between sv40 and the human polyomaviruses bk virus (bkv) and jc virus (jcv), it is debatable whether these antibodies are specific. an sv40-specific serological assay was established, based on purified virus-like particles (vlps), where the sv40 vlps were blocked with hyperimmune sera ...200515914848
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