Explore the vast range of titles available.

BackgroundThe replication of BK virus (BKV) and JC virus (JCV) is linked to polyomavirus-associated nephropathy, hemorrhagic cystitis, and multifocal leukoencephalopathy in immunodeficient patients, but the behavior of these viruses in immunocompetent individuals has hardly been characterized MethodsWe used EIA to study samples obtained from 400 healthy blood donors aged 20–59 years for BKV- and JCV-specific antibodies against virus-like particles. We also studied BKV and JCV loads in plasma and urine among these individuals by use of real-time polymerase chain reaction ResultsIgG seroprevalence was 82% (328 of 400 donors) for BKV and 58% (231 of 400) for JCV. As age increased (age groups were divided by decade), the seroprevalence of BKV decreased from 87% (87 of 100) in the youngest group (aged 20–29 years) to 71% (71 of 100) in the oldest group (aged 50–59 years) (P=.006), whereas the seroprevalence of JCV increased from 50% (50 of 100) in the youngest group to 68% (68 of 100) in the oldest group (P=.06). Asymptomatic urinary shedding of BKV and JCV was observed in 28 (7%) and 75 (19%) of 400 subjects, respectively, with median viral loads of 3.51 and 4.64 log copies/mL, respectively (P<.001). Unlike urinary BKV loads, urinary JCV loads were positively correlated with IgG levels. The shedding of JCV was more commonly observed among individuals who were seropositive only for JCV, compared with individuals who were seropositive for both BKV and JCV, suggesting limited cross-protection from BKV immunity. Noncoding control regions were of archetype architecture in all cases, except for 1 rearranged JCV variant. Neither BKV nor JCV DNA was detected in plasma ConclusionsOur study provides important data about polyomavirus infection and replication in healthy, immunocompetent individuals. These data indicate significant differences between BKV and JCV with respect to virus-host interaction and epidemiology

Recent studies have established that the human urine contains a complex microbiome, including a virome about which little is known. Following immunosuppression in kidney transplant patients, BK polyomavirus (BKV) has been shown to induce nephropathy (BKVN), decreasing graft survival. In this study we investigated the urine virome profile of BKV+ and BKV− kidney transplant recipients. Virus-like particles were stained to confirm the presence of VLP in the urine samples. Metagenomic DNA was purified, and the virome profile was analyzed using metagenomic shotgun sequencing. While the BK virus was predominant in the BKV+ group, it was also found in the BKV− group patients. Additional viruses were also detected in all patients, notably including JC virus (JCV) and Torque teno virus (TTV) and interestingly, we detected multiple subtypes of the BKV, JCV and TTV. Analysis of the BKV subtypes showed that nucleotide polymorphisms were detected in the VP1, VP2 and Large T Antigen proteins, suggesting potential functional effects for enhanced pathogenicity. Our results demonstrate a complex urinary virome in kidney transplant patients with multiple viruses with several distinct subtypes warranting further analysis of virus subtypes in immunosuppressed hosts.

Progressive multifocal leukoencephalopathy (PML), a fatal demyelinating disease caused by JC virus (JCV) infection of oligodendrocytes, may develop in patients with immune disorders following reactivation of chronic benign infection. Mutations of JCV capsid viral protein 1 (VP1), the capsid protein involved in binding to sialic acid cell receptors, might favor PML onset. Cerebrospinal fluid sequences from 37/40 PML patients contained one of several JCV VP1 amino acid mutations, which were also present in paired plasma but not urine sequences despite the same viral genetic background. VP1-derived virus-like particles (VLPs) carrying these mutations lost hemagglutination ability, showed different ganglioside specificity, and abolished binding to different peripheral cell types compared with wild-type VLPs. However, mutants still bound brain-derived cells, and binding was not affected by sialic acid removal by neuraminidase. JCV VP1 substitutions are acquired intrapatient and might favor JCV brain invasion through abrogation of sialic acid binding with peripheral cells, while maintaining sialic acid-independent binding with brain cells.

In the fifty years since the discovery of JC polyomavirus (JCPyV), the body of research representing our collective knowledge on this virus has grown substantially. As the causative agent of progressive multifocal leukoencephalopathy (PML), an often fatal central nervous system disease, JCPyV remains enigmatic in its ability to live a dual lifestyle. In most individuals, JCPyV reproduces benignly in renal tissues, but in a subset of immunocompromised individuals, JCPyV undergoes rearrangement and begins lytic infection of the central nervous system, subsequently becoming highly debilitating—and in many cases, deadly. Understanding the mechanisms allowing this process to occur is vital to the development of new and more effective diagnosis and treatment options for those at risk of developing PML. Here, we discuss the current state of affairs with regards to JCPyV and PML; first summarizing the history of PML as a disease and then discussing current treatment options and the viral biology of JCPyV as we understand it. We highlight the foundational research published in recent years on PML and JCPyV and attempt to outline which next steps are most necessary to reduce the disease burden of PML in populations at risk.

Highlights A significant proportion of 35/60 (58.33%) tumor tissue and 42/60 (70%) urine samples of the CRC patients were found to be positive for JCV DNA ( P  = 0.25). The parallel analysis of tumor and urine samples for JCV DNA further supports the potential for non-invasive screening tools. screening JCV DNA in peripheral blood mononuclear cells (PBMCs) and stool of CRC patients may further support the potential for non-invasive screening tools. The study offers new insights into rearranged NCCR variants isolated from colorectal cancer (CRC) patients’ tissue. The screening and analysis of the rrNCCR region of JCV DNA in CRC patients’ stool may indicate the pathogenesis of the JCV virus in CRC development. The presence of JCV LTAg in tumor tissue is significantly higher than in normal tissue (p = < 0.002), suggesting JCV’s role in cancer development during the latency phase. Background Several studies have reported the presence of JC virus (JCV) in human tumors, The association of JCV and CRC remains controversial. This study aimed to evaluate the rearranged NCCR region of the detected JCV DNA in CRC patients’ tissue samples. Methods In this case-control study, tumor tissues ( n  = 60), adjacent normal tissues ( n  = 60), and urine samples ( n  = 60) of the CRC patients were collected. The nested PCR was employed to detect the VP1 and NCCR regions of the JCV genome. The positive JCV PCR products were sequenced and a phylogenetic tree was constructed to determine the JCV genotypes. After extracting RNA and preparing cDNA, the expression of JCV LTAg was examined in 60 tumor tissues and 60 adjacent normal tissues. The analysis of JCV LTAg expression was performed using GraphPad Prism software version 8. Results The analysis reveals that JCV DNA was detected in 35/60 (58.3%) tumor tissues, while 36/60 (60.0%) of adjacent normal tissues ( p  = 0.85). JCV DNA was detected in 42/60 (70.0%) urine samples when compared to 35/60 (58.3%) tumor tissues of CRC patients and was not found significant ( P  = 0.25). The phylogenetic tree analysis showed the dominant JCV genotype 3, followed by genotype 2D was distributed in tumor tissue, normal tissue, and urine samples of the CRC patients. Analysis of randomly selected NCCR sequences from JCV regions in tumor tissue samples revealed the presence of rearranged NCCR blocks of different lengths.: 431 bp, 292 bp, 449 bp, and 356 bp. These rearranged NCCR blocks differ from the rearranged NCCR blocks described in PML-type Mad-1, Mad-4, Mad-7, and Mad-8 prototypes. The expression of JCV LTAg was significantly different in tumor tissue compared to normal tissue, with a p-value of less than 0.002. Conclusion A significant proportion of 35%> of the tumor tissue and urine samples of the CRC patients was found to be positive for JCV DNA ( P  = 0.25). The parallel analysis of tumor and urine samples for JCV DNA further supports the potential for non-invasive screening tools. This study provides new insights into Rearranged NCCR variant isolates from patients with CRC. The significant difference in JCV LTAg expression between tumor and normal tissue indicates a latent JCV status potentially leading to cancer development.

JC Polyomavirus (JCV) is a human polyomavirus encoding T-antigen protein, which is implicated in carcinogenesis. JCV is prevalent in the upper and lower gastrointestinal track. Several studies have reported JCV associations with the risk of developing colorectal cancer (CRC), however, these findings remain controversial. Since JCV DNA may be present in healthy tissues as well as transformed tissues, JCV T-antigen expression could be a more useful measure of JCV’s association with cancer development. The aim of this study is to conduct a meta-analysis of case-control studies to investigate if there is a significant association between JCV T-antigen protein expression and risk of CRC. A systematic review was performed to identify studies reporting JCV DNA prevalence in CRC and JCV T-antigen expression. The strength of the association was estimated by odds ratios (ORs). Five (of 66) studies satisfied analysis inclusion criteria, and spanned years 1999 to 2022. Random effects meta-analysis of CRC cases versus controls showed an 11-fold increased risk of CRC development in JCV DNA positive samples with JCV T-antigen expression versus normal tissues (OR 10.95; 95% CI: 2.48–48.24; P = 0.0016). The results of this meta-analysis of JCV infection followed by JCV T-antigen protein expression for the risk of CRC support the argument that JCV infection significantly increases the risk of colorectal cancer in tissues where the JCV T-antigen protein is expressed. Further research with JCV T-antigen expression in relation to CRC development is needed.

Progressive Multifocal Leukoencephalopathy (PML) is a rare, often fatal demyelinating disease of the central nervous system caused by reactivation of the John Cunningham virus (JCV) in immunocompromised individuals. Despite an estimated 2.4 million people living with HIV in India, the reported incidence of PML remains lower than in Western countries, likely due to underdiagnosis, underreporting, and distinct host genetic and viral factors. The rising number of individuals on immunosuppressive therapies, including organ transplant recipients and those with autoimmune disorders, further emphasizes the need to study JC virus diversity in the Indian context. This study aimed to characterize the genetic diversity of JCV in India by sequencing the VP1 and non-coding control region (NCCR) from cerebrospinal fluid (n=30) of confirmed PML cases using Sanger sequencing. VP1 sequencing (n=23) revealed a predominance of genotypes 2 (subtypes 2D, 2A, 2B) and 3A. NCCR analysis (n=17) showed extensive rearrangements relative to the archetype form, with most sequences classified as Type II-R. Structural variations, including deletions, duplications, and insertions were common, particularly in blocks D, C, and F. Transcription factor binding sites (TFBS) were identified for TATA box, Tst-1, SP-1, p53, CEBPB, AP-1, NF-1, EGR-1, GF-1, CRE-TAR and NFkB. Additional TFBS were created due to rearrangements, often spanning two blocks. These findings underscore the genomic diversity of JCV in India and highlight the need for continued molecular surveillance to better understand its implications for high-risk populations.

Individuals with HIV infection and two apolipoprotein L1 gene (APOL1) risk variants frequently develop nephropathy. Here we tested whether non-HIV viral infections influence nephropathy risk via interactions with APOL1 by assessing APOL1 genotypes and presence of urine JC and BK polyoma virus and plasma HHV6 and CMV by quantitative polymerase chain reaction. We analyzed 300 samples from unrelated and related first-degree relatives of African Americans with nondiabetic nephropathy using linear and nonlinear mixed models to account for familial relationships. The four groups evaluated were APOL1 zero/one versus two risk alleles, with or without nephropathy. Urine JCV and BKV were detected in 90 and 29 patients, respectively, whereas HHV6 and CMV were rare. Adjusting for family age at nephropathy, gender, and ancestry, presence of JCV genomic DNA in urine and APOL1 risk alleles were significantly negatively associated with elevated serum cystatin C, albuminuria (albumin-to-creatinine ratio over 30mg/g), and kidney disease defined as an eGFR under 60ml/min per 1.73m2 and/or albuminuria in an additive (APOL1 plus JCV) model. BK viruria was not associated with kidney disease. Thus, African Americans at increased risk for APOL1-associated nephropathy (two APOL1 risk variants) with JC viruria had a lower prevalence of kidney disease, suggesting that JCV interaction with APOL1 genotype may influence kidney disease risk.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system that is rare even though the proven etiological agent of PML, the polyomavirus JC (JC virus), is ubiquitous within the human population. The common feature of PML cases appears to be underlying immunosuppression, and PML has gained clinical visibility because of its association with human immunodeficiency virus and AIDS and its occurrence as a side effect of certain immunomodulatory drugs. A hypothesis has gained general acceptance that JC virus causes a primary infection in childhood and enters a latent state, after which immunosuppression allows viral reactivation leading to PML. Nonetheless, many important aspects of PML pathogenesis remain unclear, including the molecular bases of latency and reactivation, the site(s) of latency, the relationship of archetype and prototype virus and the mode of virus transmission within the body and between individuals. In this review, we will revisit these areas and examine what the available evidence suggests.

Progressive multifocal leukoencephalopathy (PML) is a rare complication of natalizumab treatment and is caused by the JC virus. In this study of 19 patients with multiple sclerosis who had no symptoms of PML, the prevalence of JC virus in blood and urine increased after treatment with natalizumab. JC virus regulatory-region sequences were similar to those usually found in PML. Progressive multifocal leukoencephalopathy (PML) is a rare complication of natalizumab treatment and is caused by the JC virus. In this study of 19 patients with multiple sclerosis who had no symptoms of PML, the prevalence of JC virus in blood and urine increased after treatment with natalizumab. As of July 24, 2009, progressive multifocal leukoencephalopathy (PML), a deadly demyelinating disease of the central nervous system, had been reported in 13 patients with multiple sclerosis: 2 who were treated with a combination of natalizumab (Tysabri, Elan Pharmaceuticals and Biogen Idec) and interferon beta-1a (Avonex) 1 – 3 and 11 who received natalizumab monotherapy. 4 – 7 One additional patient with Crohn's disease who was treated with natalizumab died from PML. 8 PML is caused by the reactivation of JC virus and affects patients with the acquired immunodeficiency syndrome or leukemia and recipients of organ transplants, but it had never been reported in a . . .