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Journal of Clinical Microbiology Apr 2017BK virus (BKV)-associated diseases in transplant recipients are an emerging issue. However, identification of the various BK virus subtypes/subgroups is a long and...
BK virus (BKV)-associated diseases in transplant recipients are an emerging issue. However, identification of the various BK virus subtypes/subgroups is a long and delicate process on the basis of currently available data. Therefore, we wanted to define a simple and effective one-step strategy for characterizing all BK virus strains from the VP1 gene sequence. Based on the analysis of 199 available complete DNA VP1 sequences, phylogenetic trees, alignments, and isolated polymorphisms were used to define an effective strategy for distinguishing the 12 different BK virus subtypes/subgroups. Based on the 12 subtypes identified from the 199 complete BKV VP1 sequences (1,089 bp), 60 mutations that can be used to differentiate these various subtypes/subgroups were identified. Some genomic areas were more variable and comprised mutational hot spots. From a subregion of only 100 bp in the VP1 region (1977 through 2076), we therefore constructed an algorithm that enabled rapid determination of all BKV subtypes/subgroups with 99% agreement (197/199) relative to the complete VP1 sequence. We called this domain of the BK viral genome the BK typing and grouping region (BKTGR). Finally, we validated our viral subtype identification process in a population of 100 transplant recipients with 100% efficiency. The new simpler method of BKV subtyping/subgrouping reported here constitutes a useful tool for future studies that will help us to more clearly understand the impact of BKV subtypes/subgroups on diagnosis, infection, and BK virus-associated diseases.
Topics: BK Virus; Genetic Variation; Genotype; Genotyping Techniques; Humans; Polyomavirus Infections; Sequence Analysis, DNA; Tumor Virus Infections; Viral Structural Proteins
PubMed: 28151406
DOI: 10.1128/JCM.01180-16 -
Annals of Transplantation May 2018Human BK polyomavirus (BKV) infection is poorly documented in heart and lung transplant patients. BK viruria and viremia have been estimated to affect 19% and 5% of... (Review)
Review
Human BK polyomavirus (BKV) infection is poorly documented in heart and lung transplant patients. BK viruria and viremia have been estimated to affect 19% and 5% of heart transplant recipients, respectively. Data are limited, especially for lung transplantation, but the proportion of patients progressing from BK viruria to viremia or BKV-related nephropathy (BKVN) appears lower than in kidney transplantation. Nevertheless, a number of cases of BKVN have been reported in heart and lung transplant patients, typically with late diagnosis and generally poor outcomes. Risk factors for BKV infection or BKVN in this setting are unclear but may include cytomegalovirus infection and anti-rejection treatment. The relative infrequency of BKVN or other BK-related complications means that routine BKV surveillance in thoracic transplantation is not warranted, but a diagnostic workup for BKV infection may be justified for progressive renal dysfunction with no readily-identifiable cause; after anti-rejection therapy; and for renal dysfunction in patients with cytomegalovirus infection or hypogammaglobulinemia. Treatment strategies in heart or lung transplant recipients rely on protocols developed in kidney transplantation, with reductions in immunosuppression tailored to match the higher risk status of thoracic transplant patients.
Topics: BK Virus; Female; Heart Transplantation; Humans; Kidney Transplantation; Lung Transplantation; Male; Polyomavirus Infections; Risk Factors; TOR Serine-Threonine Kinases; Tumor Virus Infections; Viremia
PubMed: 29748530
DOI: 10.12659/AOT.908429 -
American Journal of Transplantation :... Sep 2019
Topics: BK Virus; Cytomegalovirus; Cytomegalovirus Infections; Humans; Polyomavirus Infections; Viremia
PubMed: 31306544
DOI: 10.1111/ajt.15531 -
Annals of Agricultural and... Sep 2017Colorectal cancer is one of the most common cancers worldwide. In Poland, it is the second most common cancer, regardless of gender. The aim of study was to analyze the...
INTRODUCTION AND OBJECTIVE
Colorectal cancer is one of the most common cancers worldwide. In Poland, it is the second most common cancer, regardless of gender. The aim of study was to analyze the incidence of HPV and BKV in the tissue of colorectal cancer and to determine the relationship between the presence of these viruses and the development of this cancer.
MATERIAL AND METHODS
The experiments were conducted using 50 colorectal cancer tissues collected from histological sections. The clinical material was embedded in paraffin blocks. Next, DNA extraction was performed. Isolates of colorectal cancer tissue were tested for the presence of HPV DNA. BKV DNA was detected by PCR using specific primers and then differentiated from JCV by digestion with BamHI enzyme.
RESULTS
In clinical specimens taken from patients with colorectal cancer, HPV DNA was detected in 20% of cases. In 10% of cases the presence of HPV type 18 was confirmed, in the other 90% of the samples HPV type 16 was detected, while the presence of BKV was confirmed in 30% of cases. Coinfection with HPV and BKV was shown in 12% of patients. In one case, BK virus coexisted with HPV type 18, in the remaining 5 cases with HPV type 16.
CONCLUSIONS
Developing colorectal cancer can show no symptoms, even for many years. This is why it is so important to become familiar with as many etiological factors as possible. The development of many human neoplasms is often initiated by exposure to infectious agents - such as bacterial or viral infections. Similar to the human papillomavirus, the BK virus was detected in clinical specimens. It seems that HPV and BKV infections can contribute to the neoplastic process, which requires detailed studies on a larger group of patients.
Topics: Adult; Aged; BK Virus; Colorectal Neoplasms; Female; Humans; Male; Middle Aged; Papillomaviridae; Papillomavirus Infections; Polymerase Chain Reaction; Polyomavirus Infections
PubMed: 28954487
DOI: 10.26444/aaem/74648 -
Blood Advances May 2020Clinical disease caused by BK virus reactivation is a frequent complication of allogeneic hematopoietic cell transplantation (HCT). Because of the lack of effective...
Clinical disease caused by BK virus reactivation is a frequent complication of allogeneic hematopoietic cell transplantation (HCT). Because of the lack of effective antiviral agents, BK virus-specific T cells are emerging as a potential therapy for BK virus disease, but the immune response to BK virus after allogeneic HCT has not been well characterized. Our study describes reconstitution of BK virus-specific T-cell immunity in 77 adult patients after HCT. All patients had urinary symptoms, and urine was tested for BK virus replication; 33 patients were positive for BK virus (cases), and 44 were negative (controls). In BK virus cases, the median time to first positive test was 75 days (range, 2-511). BK virus cases had lower CD4 T-cell counts 3 to 9 months after transplant, but CD8 T-cell counts were similar in cases and controls. BK virus-specific T cells were identified by cytokine flow cytometry in cryopreserved samples collected prospectively. BK virus-specific CD4 T cells producing T helper 1 (Th1) cytokines recovered quickly after HCT. BK virus-specific T cells were detected more frequently in patients with BK virus reactivation at most time points, and CD4 T cells producing Th1 cytokines were more frequent than BK virus-specific cytolytic CD8 T cells. Early detection of interferon-γ+ and cytolytic BK virus-specific CD4 T cells was associated with lower rates of hematuria among cases. Overall, our study describes recovery of BK virus-specific T cells after HCT and the distinct roles for BK virus-specific T cells in the development and resolution of clinical symptoms.
Topics: Adult; BK Virus; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Hematopoietic Stem Cell Transplantation; Humans; Immune Reconstitution
PubMed: 32374880
DOI: 10.1182/bloodadvances.2019001120 -
World Journal of Gastroenterology Jan 2016Polyomavirus BK (BKV) infects up to 90% of the general population. After primary infection, occurring early during childhood, a state of non-replicative infection is... (Review)
Review
Polyomavirus BK (BKV) infects up to 90% of the general population. After primary infection, occurring early during childhood, a state of non-replicative infection is established in the reno-urinary tract, without complications for immunocompetent hosts. In immunocompromised individuals, particularly transplanted patients, asymptomatic BKV viremia and/or viruria can be observed. Renal grafts may also be sources of infection as BKV prefers kidneys rather than other solid organs for transplantation such as the liver. The mechanism behind the higher incidence of BKV infection in kidney transplant patients, compared to liver or heart transplantation, is unclear and the prevalence of BKV infection in non-renal solid organ transplants has not been yet thoroughly investigated. We evaluated the prevalence of Polyomavirus BK infection among liver transplant recipients. A PubMed search was conducted using the terms BKV infection AND liver transplant recipients; BKV AND non-renal solid organ transplant*; BKV infection AND immunosuppression; the search was limited to title/abstract and English-language articles published from 2000, to March 2015. Eleven relevant studies suggest that the prevalence of BKV viruria and/or viremia among liver transplant recipients is less than that reported in kidney or heart transplant recipients, except when chronic kidney disease (CKD) is present at the same time. Data also suggest that viruric and viremic patients have higher levels of serum creatinine than BKV negative patients. Moreover, no specific immunosuppressive drugs are associated with the onset of BKV nephropathy. The comorbidity of transplantation and CKD could play a major role in promoting BKV replication.
Topics: BK Virus; Comorbidity; Humans; Immunocompromised Host; Immunosuppressive Agents; Liver Transplantation; Opportunistic Infections; Polyomavirus Infections; Prevalence; Renal Insufficiency, Chronic; Risk Factors; Treatment Outcome; Tumor Virus Infections; Virus Activation; Virus Replication
PubMed: 26819520
DOI: 10.3748/wjg.v22.i4.1532 -
Intervirology 2021Members of the Polyomaviridae family, BK virus (BKV), and John Cunningham virus (JCV) are linked to polyomavirus-associated nephropathy-associated transplant rejection...
BACKGROUND
Members of the Polyomaviridae family, BK virus (BKV), and John Cunningham virus (JCV) are linked to polyomavirus-associated nephropathy-associated transplant rejection in immunodeficient patients.
OBJECTIVE
The aim of the study was to evaluate the prevalence of BKV and JCV in immunocompetent individuals in the north of Iran.
METHODS
Ninety-one urine samples were obtained from renal transplant recipients with a mean age of 39.78 ± 11.19 years. A healthy control group of 65 volunteers with an average age of 40.32 ± 10.7 years also contributed. After DNA extraction, positive cases were detected through PCR. Genotyping was done by alignment and phylogenetic tree construction of the VP1 region against all known JCV and BKV genotypes.
RESULTS
The prevalence of BKV and JCV was 15.38 and 19.78%, respectively. JCV was detected in 7.69% of the control group. The prevalence of the BKV between the case and control groups was significant (p < 0.0001). There was no significant association between BKV and JCV and duration of dialysis (p > 0.05). Overall, 62.16% of JCV cases were genotype I. Besides, genotype II was dominant within patients with BKV-positive patients.
DISCUSSION
The results obtained here show a relatively lower prevalence of BKV and JCV in immunocompromised renal transplant receivers and healthy control than those reported from other areas in Iran. JCV genotyping was evaluated for the first time in Iran. Genotype I for JCV and genotype II for BKV were dominant genotypes in the north of Iran.
Topics: Adult; BK Virus; Caspian Sea; DNA, Viral; Humans; JC Virus; Kidney Transplantation; Middle Aged; Phylogeny; Polyomavirus Infections; Transplant Recipients; Tumor Virus Infections
PubMed: 33596566
DOI: 10.1159/000513369 -
Seminars in Cancer Biology Aug 2009BK virus (BKV) is a polyomavirus that ubiquitously infects the human population. Following a typically subclinical primary infection, BKV establishes a life-long... (Review)
Review
BK virus (BKV) is a polyomavirus that ubiquitously infects the human population. Following a typically subclinical primary infection, BKV establishes a life-long persistent infection in the kidney and urinary tract. BKV is known to reactivate and cause severe disease in immunosuppressed patients, particularly renal and bone marrow transplant patients. Infection of BKV in rodent animal models or cells in culture often results in tumor formation or transformation, respectively. When co-expressed with activated oncogenes, BKV large tumor antigen drives the transformation of primary human cells. An etiological role of BKV in human cancer, however, remains controversial. Multiple reports have demonstrated conflicting results in regards to the presence of BKV sequences and/or proteins in various tumor types. This review compiles the most recent findings of BKV detection in a number of human cancers. Due to the lack of conclusive causality data from these studies, there does not appear to be a definitive association between BKV and human cancers.
Topics: Animals; BK Virus; Humans; Neoplasms; Polyomavirus Infections; Tumor Virus Infections
PubMed: 19505653
DOI: 10.1016/j.semcancer.2009.02.004 -
Nephrology, Dialysis, Transplantation :... Dec 2008We investigated the expression of early and late phase BK virus (BKV) proteins and their interactions with host cell proteins in renal allografts, with ongoing... (Review)
Review
OBJECTIVE
We investigated the expression of early and late phase BK virus (BKV) proteins and their interactions with host cell proteins in renal allografts, with ongoing polyomavirus associated nephropathy (PVAN), and correlated this with the nuclear and cell morphology.
METHODS
Frozen sections from three patients with renal allografts (two biopsies, one explant) with PVAN were analysed by indirect immunofluorescence using BKV specific anti-polyoma large T-antigen and anti-VP-1 antibodies, as well as anti-p53, anti-Ki67, anti-caspase-3, anti-bcl2 and anti-cytokeratin 22 antibodies. Nuclear morphology and size were estimated by DNA Hoechst staining.
RESULTS
In infected tubular cells the early and late phases of infection could be distinguished according to expression of large T-antigen or VP-1. The early phase revealed almost normal nuclear proportions, whereas in later phases nuclear size increased about 2 to 3 fold. Expression of large T-antigen was strongly associated with accumulation of p53 in the nucleus, accompanied by the activation of the cell cycle associated cell protein Ki67. In contrast, expression of BKV VP1 correlated only weakly with p53. Virus dependent cell lysis was due to necrosis, since neither caspase 3 nor nuclear nor cytoskeleton changes indicated apoptosis.
CONCLUSION
In our selected patients with PVAN a clear distinction between early and late phases was possible, according to the protein expression patterns of BKV markers. Striking nuclear enlargement is only present in the late phase of infection. In the inflammatory setting of PVAN, BKV dependent effects appear to be mediated by the inhibition of p53, resulting in the activation of the cell cycle. We assume that in PVAN similar BKV mechanisms are operative as in certain in vitro systems.
Topics: Adult; Aged; Antigens, Viral, Tumor; Apoptosis; BK Virus; Caspase 3; Female; Host-Pathogen Interactions; Humans; Keratins; Ki-67 Antigen; Kidney Diseases; Kidney Transplantation; Middle Aged; Polyomavirus Infections; Proto-Oncogene Proteins c-bcl-2; Tumor Suppressor Protein p53; Tumor Virus Infections; Viral Structural Proteins
PubMed: 18784088
DOI: 10.1093/ndt/gfn470 -
Experimental and Clinical... Jan 2020The main function of HLA is to present antigens to lymphocytes and to initiate specific immune responses. Autoimmune, viral, allergic, and neurologic diseases have been...
OBJECTIVES
The main function of HLA is to present antigens to lymphocytes and to initiate specific immune responses. Autoimmune, viral, allergic, and neurologic diseases have been found to be related to HLA molecules. In renal transplant, the main target of the recipient's immune system is the HLA molecules on the surface of donor cells. HLA also plays a role in the development of an immune response to viral infections. After renal transplant, BK virus infections may occur due to immunosuppression. Here, we investigated the relationship between HLA and BK virus in renal transplant recipients.
MATERIALS AND METHODS
This retrospective study investigated HLA-A, HLA-B, and HLA-DR tissue typing before renal transplant. DNA was isolated from whole blood, and tissue typing tests were performed based on polymerase chain reaction. Patients were tested for BK virus posttransplant using DNA isolated from urine and/or plasma samples.
RESULTS
We found HLA-B*13 allele to be a protective factor (P < .049; odds ratio: 0.131; 95% confidence interval, 0.017-1.029) and HLA-DRB1*03 allele to be a possible risk factor (P < .029; odds ratio: 2.521; 95% confidence interval, 1.157-5.490) against BK virus. No significant relationships were found between BK virus and age, sex, donor type, and HLA mismatch.
CONCLUSIONS
HLA class I molecules are known to be effective against viruses with the help of cytotoxic T cells. HLA-B*13 alleles within the HLA class I molecules were identified as protective factors against BK virus. HLA class II is associated with CD4-positive T cells that help secrete immune system cytokines, playing a role in stimulating and suppressing the immune system. We demonstrated that HLA-DRB1*03 allele could be a risk factor against BK virus. This allele may be associated with immunomodulatory cytokine secretion of the immune system.
Topics: BK Virus; DNA, Viral; Female; Gene Frequency; HLA Antigens; Host-Pathogen Interactions; Humans; Immunocompromised Host; Immunosuppressive Agents; Kidney Transplantation; Male; Opportunistic Infections; Polyomavirus Infections; Retrospective Studies; Treatment Outcome; Tumor Virus Infections; Viral Load
PubMed: 32008495
DOI: 10.6002/ect.TOND-TDTD2019.O24