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Background: Prostate cancer (PC) represents the most frequently diagnosed cancer in men. Exposure to infectious agents has been considered to induce prostatic inflammation and cancerous transformation. Controversial data exist concerning the role of the human polyomaviruses BK (BKV) and JC (JCV) in PC etiology. Therefore, a possible association between these polyomaviruses and PC was investigated., Materials and Methods: Urine, blood and fresh prostatic tissue specimens were collected from 26 patients with PC. The presence of BKV and JCV, the possible non-coding control region (NCCR) variations and the genotyping analysis of viral protein 1 (VP1) of both viruses were assessed., Results: Data showed a preferential viral re-activation in the urinary compartment and a statistically significant prevalence of JC viruria and of BKV in PC tissues. A BKV DDP-like NCCR sequence was isolated in two patients, whereas JCV NCCR was consistently of an archetypal structural organization. A prevalence of the European genotypes was observed for both viruses., Conclusion: Our data demonstrated the presence of JCV DNA in 14/24 (58.3%) cancerous prostatic tissue specimens, confirming the results obtained in a previous study, in which JCV has been defined as common inhabitant of the prostate, and opening the discussion about its potential role in PC., (Copyright© 2015, International Institute of Anticancer Research (Dr. John G. Delinasios), All rights reserved.)

Background: Nowadays, better immunosuppressors have decreased the rates of acute rejection in kidney transplantation, but have also led to the emergence of BKV-associated nephropathy (BKVAN). Therefore, we prospectively investigated BKV load in plasma and urine samples in a cohort of kidney transplants, receiving basiliximab combined with a mycophenolate mofetil-based triple immunotherapy, to evaluate the difference between BKV replication during the first 3 months post-transplantation, characterized by the non-depleting action of basiliximab, versus the second 3 months, in which the maintenance therapy acts alone. We also performed sequencing analysis to assess whether a particular BKV subtype/subgroup or transcriptional control region (TCR) variants were present., Methods: We monitored BK viruria and viremia by quantitative polymerase chain reaction (Q-PCR) at 12 hours (Tx), 1 (T1), 3 (T2) and 6 (T3) months post-transplantation among 60 kidney transplant patients. Sequencing analysis was performed by nested-PCR with specific primers for TCR and VP1 regions. Data were statistically analyzed using χ² test and Student's t-test., Results: BKV was detected at Tx in 4/60 urine and in 16/60 plasma, with median viral loads of 3.70 log GEq/mL and 3.79 log GEq/mL, respectively, followed by a significant increase of both BKV-positive transplants (32/60) and median values of viruria (5.78 log GEq/mL) and viremia (4.52 log GEq/mL) at T2. Conversely, a significantly decrease of patients with viruria and viremia (17/60) was observed at T3, together with a reduction of the median urinary and plasma viral loads (4.09 log GEq/mL and 4.00 log GEq/mL, respectively). BKV TCR sequence analysis always showed the presence of archetypal sequences, with a few single-nucleotide substitutions and one nucleotide insertion that, interestingly, were all representative of the particular subtypes/subgroups we identified by VP1 sequencing analysis: I/b-2 and IV/c-2., Conclusions: Our results confirm previous studies indicating that BKV replication may occur during the early hours after kidney transplantation, reaches the highest incidence in the third post-transplantation month and then decreases within the sixth month, maybe due to induction therapy. Moreover, it might become clinically useful whether specific BKV subtypes or rearrangements could be linked to a particular disease state in order to detect them before BKVAN onset.

The recent introduction of monoclonal antibodies in Crohn's disease (CD) management has been associated with the development of serious complications, such as the progressive multifocal leukoencephalopathy (PML), caused by JC polyomavirus (JCV) reactivation. Therefore, the aims of our study have been the investigation of the possible JCV reactivation in pediatric CD patients treated or not with infliximab, performing quantitative PCR in urine, plasma, and intestinal biopsies at the time of recruitment (t0) and every 4 months in 1 year of follow-up (t1, t2, and t3), and the analysis of the JCV noncoding control region (NCCR) to detect cellular transcription factors binding site mutations. Results obtained showed that, in urine and ileal specimens, JCV load significantly increased in infliximab-treated patients after 1 year of treatment (t3), while viremia was significantly higher at t1. JCV NCCR sequence analysis showed a structure similar to CY archetype in 65/80 analyzed sequences, but the remaining 15/80, obtained exclusively from plasma and biopsies, evidenced a CY NCCR organization with two recurrent nucleotide changes, the 37-T to G transversion in box A Spi-B binding site and the 217-G to A transition in box F, and a box D deletion. These rearrangements were always found at t3 within seven infliximab-treated CD patients, who presented a very severe disease at t0. We can conclude that our rearranged NCCR sequences could be considered a marker of JCV virulence during mAb treatment, although none of our examined patients developed PML, and further studies on a larger cohort of patients should be performed.

Hemorrhagic cystitis is characterized by hematuria due to inflammation of the bladder. In bone marrow transplants, this disease is linked to the infection by human polyomavirus BK, whereas the role of the human polyomavirus JC is unclear. The transcriptional control regions of both viruses contain important cellular transcription factor binding sites that undergo rearrangement process generating suitable variants that could be more active for viral replication and for the onset of hemorrhagic cystitis. In this study urine obtained from seven patients with bone marrow transplant were examined. Polyomavirus genomes were quantified by PCR and viral loads were compared. The transcriptional regions of both viruses were amplified and sequenced to determine the presence of variants. Subtypes of polyomaviruses were determined by amplification and sequencing of the viral protein 1 region. The results showed that four of seven patients were positive for BK DNA, two of seven patients had BK and JC DNA and one of seven had JC DNA. Positive samples were amplified and sequenced successively for transcriptional regions. The viral archetype was always found in both viruses. Finally, typing showed that BK virus subtype I infected patients with BK, whereas JC virus genotype IA and genotype 1B were found in patients infected with JC. The data suggest that new and different approaches are required to improve the morbidity and mortality caused by polyoma-associated hemorrhagic cystitis, since it known that BK virus is involved in the onset of hemorrhagic cystitis, whereas the role of JC virus should be investigated further., ((c) 2009 Wiley-Liss, Inc.)

BKV associated nephropathy (BKVAN) is a cause of renal dysfunction and loss of the graft in transplants. Viral primary infection is usually inapparent and then BKV establishes latency in kidneys. Reactivation occurs in immunocompromised conditions in renal transplant recipients who can develop a subclinical nephritis and eventually a BKV-associated interstitial nephritis or a BKVAN. In this study, we searched for BKV copies in urine and plasma of renal transplants by quantitative assay (QPCR). Results showed that in several patients clearance of viremia is associated with persistent viruria, suggesting that both specimens are necessary to correctly monitor a BKVAN.

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system whose pathological features consist of white matter plaques of primary demyelinization and loss of oligodendrocytes. Various risk factors have been associated with MS susceptibility. We have focused this study on different viruses. In particular in the present study we used PCR to search for the genomic DNA of HHV-1, HHV-2, HHV-8, BKV and JCV in urine and peripheral blood mononuclear cells (PBMC) samples from 44 relapsing-remitting MS (RRMS) patients. No viral DNA was found in any urine sample, whereas 29.5% of RRMS PBMC samples were positive. It is suggestive that Human herpesviruses (HHV-1 and HHV-8) were constantly present in all positive samples, indicating that viral agents could contribute to create the demyelination plaques and cause MS.

Hemorrhagic cystitis (HC) is a well-known complication after allogeneic bone marrow transplant (BMT) and can be related to adenovirus or human polyomavirus BK (BKV) infections. In this study a group of 20 patients after allogeneic BMT has been examined. BMT urine samples were analysed for the presence of Adenovirus and BKV DNAby means of polymerase chain reaction (PCR). 5/20 BMT patients developed HC after BMT. The presence of BKV DNA in urine samples was evident in 3/15 patients without HC and in 5/5 patients with HC. In 2/5 HC-patients the BKV DNA was not found after therapy with Cidofovir and Ribavirin. The search for adenovirus DNA in all samples was negative. The analysis of BKV non-coding control region (NCCR) isolated from urine samples revealed a structure very similar to the archetype in all samples. The RFLP (Restriction Fragment Length Polymorphism assay) showed the presence of BKV subtypes I and IV, with the prevalence of subtype I (4/5). This study supports the hypothesis that HC is mainly related to BKV rather than to adenovirus infection in BMT patients. Moreover, since BKV subtype I was predominant, it is reasonable to hypothesize that a specific BKV subtype could be associated with the development of HC.