BACKGROUND: Hemorrhagic cystitis(HC), a common complication of bone marrow transplantation(BMT), is known to be associated with toxic metabolites of chemotherapy drugs or reactivation of primary virus infections. In this study, we evaluated the association between polyomaviruria and HC in BMT patients. METHODS: Urine specimens of 29 patients with HC after BMT were requested for the detection of polyomavirus by culture and polyomerase chain reaction(PCR). Several clinical parameters were analyzed in relations to the presence of polyomaviruria. For comparison, 19 patients without HC after BMT were involved in this study. RESULTS: Overall, 45 of 558 patients developed HC after BMT, and the incidence of HC was estimated to be 8.1%. Patients group showed significantly high prevalence of BK viruria compared with control group by PCR(72.4% vs 31.6%, P = 0.005). In patients group, BK virus was isolated in 44.8%(13/29) by culture and detected in 72.4%(21/29) by PCR. Results of both methods were agreed in 65.5%(19/29). JC virus was detected in 6.9%(2/29) by PCR. Sex, conditioning regimen, graft-versus-host disease(GVHD), onset time after BMT and duration of hematuria did not show any statistically significant differences between the two groups based on the presence of BK viruria by PCR. CONCLUSIONS: High prevalence of BK viruria in HC patients after BMT suggests the possible association between BK virus and HC. However, we could not find any significant clinical parameters in association with BK viruria.
BK Virus ; Bone Marrow Transplantation ; Bone Marrow* ; Cystitis* ; Drug Therapy ; Hematuria ; Humans ; Incidence ; JC Virus ; Polymerase Chain Reaction ; Polyomavirus ; Prevalence

WU polyomavirus (WUPyV), a new member of the genus Polyomavirus in the family Polyomaviridae, is recently found in patients with respiratory tract infections. In our study, the complete genome of the two WUPyV isolates (FZ18, FZTF) were sequenced and deposited in GenBank (accession nos. FJ890981, FJ890982). The two sequences of the WUPyV isolates in this study varied little from each other. Compared with other complete genome sequences of WUPyV in GenBank (strain B0, S1-S4, CLFF, accession nos. EF444549, EF444550, EF444551, EF444552, EF444553, EU296475 respectively), the sequence length in nucleotides is 5228bp, 1bp shorter than the known sequences. The deleted base pair was at nucleotide position 4536 in the non-coding region of large T antigen (LTAg). The genome of the WUPyV encoded for five proteins. They were three capsid proteins: VP2, VP1, VP3 and LTAg, small T antigen (STAg), respectively. To investigate whether these nucleotide sequences had any unique features, we compared the genome sequence of the 2 WUPyV isolates in Fuzhou, China to those documented in the GenBank database by using PHYLIP software version 3.65 and the neighbor-joining method. The 2 WUPyV strains in our study were clustered together. Strain FZTF was more closed to the reference strain B0 of Australian than strain FZ18.
Adult ; Child, Preschool ; China ; Evolution, Molecular ; Genome, Viral ; genetics ; Genomics ; Humans ; Male ; Molecular Sequence Data ; Phylogeny ; Polyomaviridae ; genetics ; isolation & purification ; Sequence Analysis, DNA ; methods

The first clinical infections with polyomavirus (PV) were demonstrated in 1971, when BK virus was isolated from the urine after a kidney transplant recipient and JC virus from the brain of a patient who died of progressive multifocal leukoencephalopathy. Polyomavirus-associated nephropathy (PVAN) has become an important cause of allograft dysfunction and loss in kidney transplantation since first recognized in kidney transplant recipient with PVAN in 1995. Most cases of PVAN are caused by polyomavirus hominis type 1, known as BK virus and arise while the patient in on triple immunosuppressive combinations, often comprising tacrolimus and/or mycophenolate mofetil plus corticosteroids. Significant progress has been made, particularly in the area of diagnostic methods for PV, facilitating diagnosis, screening and monitoring of PV infection. Definitive diagnosis of PVAN requires allograft kidney biopsy. Immunologic control of PV replication can be achieved by reducing, switching, and discontinuing of the immunusuppressive agents. Cidofovir and leflunomide are used empirically in the treatment of PVAN. However, these antiviral agents are not approved for PVAN. Recently, investigational use at low-dose cidofovir (0.25~0.33 mg/kg intravenously biweekly) without probenecid should be considered for the treatment of cases refractory to decreasedmaintenance immunosuppression. PVAN had a serious consequence of kidney transplantation that increasingly cause for chronic allograft kidney loss. Despite reduction in immuo-suppression, allograft kidney loss occurred in 46% of transplant recipients with PVAN. PVAN recurred in 15% of retransplantations compared with 5% of primary kidney transplantations. However, retransplantation is not contraindicated for transplant recipient in whom a first allograft kidney lost due to PVAN. Recently, preemptive retransplantation can be considered in patients with allograft loss due to PVAN.
Adrenal Cortex Hormones ; Allografts ; Antiviral Agents ; Biopsy ; BK Virus ; Brain ; Diagnosis ; Humans ; Immunosuppression ; JC Virus ; Kidney ; Kidney Transplantation* ; Leukoencephalopathy, Progressive Multifocal ; Mass Screening ; Polyomavirus ; Probenecid ; Tacrolimus ; Transplantation

BACKGROUND: Reactivation of the polyomavirus and the use of conditioning regimen may be the causes of hemorrhagic cystitis (HC) following hematopoietic stem cell transplantation (HSCT). However, there are only a few reports on the clinical characteristics of viral reactivation in HC following HSCT in Korea, especially in pediatric population.METHODS: 51 patients who received HSCT in Ajou University Hospital from January 2006 to June 2012 were investigated retrospectively. 16 patients were diagnosed with HC following HSCT and were enrolled in this study. Confirmation of polyomavirus was done by polymerase chain reaction (PCR) method.RESULTS: Out of the 16 patients diagnosed with HC following HSCT, there were 5 early type HC patients and 11 late type HC patients. Positive PCR results for the BK virus (BKV) and the JC virus were found on 13 and 5 patients, respectively. 4 patients showed positive results for both viruses. For the late type HC, there were 10 patients with positive PCR results for the BKV. Cyclophosphamide was used in 33 patients, and 13 patients eventually developed HC. There was no statistical significance between the incidence of hematuria and the reactivation of the BKV or the conditioning regimens. Most patients were treated conservatively but 4 patients who showed severe hematuria or poor general condition received intravenous cidofovir. After the infusion of cidofovir, hematuria disappeared on average of 65 days and the BKV was undetectable on average of 53 days.CONCLUSION: In our study, activation of the BKV was common in patients who were diagnosed with HC following HSCT. All patients recovered from HC with conservative management and the BKV became undetectable in the majority of patients who were treated with intravenous cidofovir.
BK Virus ; Cyclophosphamide ; Cystitis ; Cytosine ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; Hematuria ; Humans ; Incidence ; JC Virus ; Korea ; Organophosphonates ; Polymerase Chain Reaction ; Polyomavirus ; Retrospective Studies

BK virus infection is one of the common complications after hematopoietic stem cell transplantation(HSCT), which is also one of the reasons of the hemorrhagic cystitis．In recent years, although there are more studies of the risk factors related with human BK virus infection after hematopoietic stem cell transplantation, the risk factors related with BKV-associated hemorrhagio cystitis(BKV-HC) remain to be elucidated. Diagnosis of BK virus infection is mainly based on quantitative PCR of blood or urine. An effective strategy for treatment of these patients is the adoptive transfer of T lymphocytes specific to virus-associated antigens. In this review, the progressis of diagnosis and treatment of BK virus infection after hematopoietic stem cell transplantation are briefly summarized.
BK Virus ; Cystitis ; Hematopoietic Stem Cell Transplantation ; Humans ; Polyomavirus Infections ; Tumor Virus Infections

Merkel cell carcinoma (MCC) is a rare neuroendocrine tumor that is highly aggressive in nature and indolent in progression. The common risk factors for MCC are senility, prolonged exposure to sunlight, and immune deficient states. Moreover, Merkel cell polyomavirus has recently been characterized to be significantly associated with pathogenesis of MCC, including the expression of Cytokeratin 20 (CK20). Diagnosis is often difficult since histopathological results require a number of differential diagnoses through immunohistochemical (IHC) stains with other cutaneous malignancies. A 67-year-old man presented with a solitary domeshaped erythematous round mass on the left upper arm for 2 months. Biopsy and IHC studies revealed findings consistent with Merkel Cell Carcinoma of neuroendocrine origin. Common IHC stains usually confirm positive findings for CK20, which is also recognized as the key component in making the diagnosis. We present a CK20 negative MCC in light of expanding the knowledge of unusually stained IHC results in MCC.
Aged ; Arm ; Biopsy ; Carcinoma, Merkel Cell* ; Coloring Agents ; Diagnosis ; Diagnosis, Differential ; Humans ; Keratin-20* ; Keratins* ; Merkel cell polyomavirus* ; Neuroendocrine Tumors ; Risk Factors ; Sunlight

Merkel cell carcinoma (MCC) is a rare neuroendocrine tumor that is highly aggressive in nature and indolent in progression. The common risk factors for MCC are senility, prolonged exposure to sunlight, and immune deficient states. Moreover, Merkel cell polyomavirus has recently been characterized to be significantly associated with pathogenesis of MCC, including the expression of Cytokeratin 20 (CK20). Diagnosis is often difficult since histopathological results require a number of differential diagnoses through immunohistochemical (IHC) stains with other cutaneous malignancies. A 67-year-old man presented with a solitary domeshaped erythematous round mass on the left upper arm for 2 months. Biopsy and IHC studies revealed findings consistent with Merkel Cell Carcinoma of neuroendocrine origin. Common IHC stains usually confirm positive findings for CK20, which is also recognized as the key component in making the diagnosis. We present a CK20 negative MCC in light of expanding the knowledge of unusually stained IHC results in MCC.
Aged ; Arm ; Biopsy ; Carcinoma, Merkel Cell ; Coloring Agents ; Diagnosis ; Diagnosis, Differential ; Humans ; Keratin-20 ; Keratins ; Merkel cell polyomavirus ; Neuroendocrine Tumors ; Risk Factors ; Sunlight

BACKGROUND: Viruria is frequently detected in patients who have had hemorrhagic cystitis (HC) following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Urinary viruses, especially BK virus, have been suggested as a cause of HC following allo-HSCT, therefore antiviral therapy is emerging as a therapeutic approach for its treatment. METHODS: Adult HC patients who underwent allo-HSCT from January 2005 to March 2006 at a single institution were enrolled. We performed a PCR-based assay for BK virus, JC virus, and CMV virus in urine obtained from the patients to determine the incidence of viruria, and the type of virus detected in the urine, and the effect of treatment with cidofovir on HC. RESULTS: Of 155 patients that received allo-HSCT during the study period, 22 (14.2%) experienced HC. A viral study of urine obtained from 19 of these 22 patients revealed that 16 (84.2%) had viruria. Eleven patients had grade III-IV HC, 5 of which were treated with intravenous cidofovir. Three of the HC patients who underwent treatment responded to cidofovir, 1 had no response, and 1 had a complete response followed by recurrence. CONCLUSION: Most adult HC patients (84.2%) had viruria following allo-HSCT, however the response rate to antiviral therapy with intravenous cidofovir for the treatment of high grade HC (grade III-IV) was 80%. Therefore, antiviral therapy should be considered if high grade HC does not respond to hyperhydration and transfusional support.
Adult* ; BK Virus ; Cystitis* ; Hematopoietic Stem Cell Transplantation* ; Hematopoietic Stem Cells* ; Humans ; Incidence ; JC Virus ; Recurrence

BACKGROUND: Merkel cell carcinoma (MCC) is an increasingly common neuroendocrine cancer of the skin. Merkel cell polyomavirus (MCPyV) is one of the causative agents of MCC. The prevalence of MCPyV in primary MCC and sun-exposed non-MCC tumors has been known to have different results depending on where it was investigated. OBJECTIVE: This study assesses the prevalence of MCPyV from primary MCC and sun-exposed non-MCC tumors in Korea. METHODS: A molecular pathology study was performed on 7 tissue specimens of MCC, 1 tissue specimen of metastatic small cell carcinoma of the lung, and 32 tissue specimens of non-MCC tumors occurring from sun-exposed areas [8 basal cell carcinomas (BCCs), 8 squamous cell carcinomas (SCCs), 8 actinic keratoses (AKs), and 8 seborrheic keratoses (SKs)]. All specimens were analyzed to determine the presence of MCPyV-DNA using both polymerase chain reaction (PCR) and real-time quantitative PCR. Immunohistochemistry with monoclonal antibody of MCPyV large T antigen (CM2B4) was also conducted. RESULTS: Using both PCR, MCPyV sequences were detected in six of seven MCC tissue specimens (85.7%). Five (71%) of seven MCC tumors were immunoreactive for CM2B4. All five immunoreactive cases were positive for MCPyV. However, there was no association of MCPyV with BCC, SCC, AK, and SK. CONCLUSION: Our results implicate that MCPyV may contribute to the pathogenesis of primary MCC, not of non-MCC skin tumors in Korea, and the persons with MCPyV infection are unusual in Korea compared to other areas.
Antigens, Viral, Tumor ; Carcinoma, Basal Cell ; Carcinoma, Merkel Cell ; Carcinoma, Small Cell ; Carcinoma, Squamous Cell ; Humans ; Immunohistochemistry ; Keratosis, Actinic ; Keratosis, Seborrheic ; Korea ; Lung ; Merkel cell polyomavirus ; Pathology, Molecular ; Polymerase Chain Reaction ; Prevalence ; Skin ; Skin Neoplasms

OBJECTIVE: To analyze the characteristics of BK polymavirus (BKV) infection and the optimal time window for intervention in kidney transplant recipients (KTRs). METHODS: We retrospectively analyzed the clinical data and treatment regimens in 226 KTRs in our center between January, 2013 and January, 2018. Among the recipients, 157 had a urine BKV load ≥1.0×10 copy/mL after transplantation, and 69 had a urine BKV load below 1.0×10 copy/mL (control group). RESULTS: Among the 157 KTRs, 60 (38.2%) recipients were positive for urine BKV, 66 (42.0%) had BKV viruria, and 31(19.7%) had BKV viremia. The incidence of positive urine occult blood was significantly higher in BKV-positive recipients than in the control group ( < 0.05). The change of urine BKV load was linearly related to that of Tacrolimus trough blood level (=0.351, < 0.05). In urine BKV positive group, the average estimated glomerular filtration rate (eGFR) was below the baseline level (60 mL·min·1.73 m) upon diagnosis of BKV infection reactivation, and recovered the normal level after intervention. In patients with BKV viruria and viremia, the average eGFR failed to return to the baseline level in spite of improvement of the renal function after intervention. CONCLUSIONS Positive urine occult blood after transplantation may be associated with BKV infection reactivation in some of the KTRs. BKV infection is sensitive to changes of plasma concentration of immunosuppressive agents. Early intervention of BKV replication in KTRs with appropriate dose reduction for immunosuppression can help to control virus replication and stabilize the allograft function.
BK Virus ; physiology ; Humans ; Kidney Transplantation ; Polyomavirus Infections ; virology ; Retrospective Studies ; Transplant Recipients ; Tumor Virus Infections ; virology ; Viral Load ; Virus Replication