Search Results (45)

Background/Objectives: The genitourinary microbiome and metabolome may contribute to prostate cancer (PC) biology, but evidence remains limited. This pilot study characterizes the urinary microbiota and volatilome in men with PC and investigates microbial and viral DNA in prostate tissue, comparing findings with benign prostatic hyperplasia (BPH). Methods: We prospectively enrolled 21 non-metastatic PC patients undergoing radical prostatectomy and 17 BPH controls. Lesional and non-lesional prostate tissues and urine were collected from PC patients, as well as urine samples from BPH participants. DNA samples were tested for sexually transmitted pathogens by multiplex real-time PCR. Urine and prostate tissue were analyzed for human polyomaviruses (JCPyV, BKPyV, MCPyV) by qPCR, bacterial profiles via 16S rRNA gene sequencing, and urinary volatile organic metabolites (VOMs) using HS-SPME/GC-MS. Microbial and metabolic profiles were compared, and taxa–metabolites were assessed. Results: JCPyV and BKPyV were detected in urine and tissue from PC patients; MCPyV was detected only in tissue, at low frequency. In BPH, viral prevalence was lower and MCPyV was absent. JCPyV/BKPyV co-infection was common in cancer. No sexually transmitted pathogen emerged. PC patients showed greater urinary microbial diversity and five enriched genera, along with specific metabolic pathways. 36 urinary VOMs were identified, with 14 differing significantly, with positive correlations between PC-associated genera and metabolites. In contrast, prostate tissue was low-biomass, dominated by Pseudomonas, and showed no significant differences between lesional and non-lesional areas. Conclusions: This preliminary, hypothesis-generating study indicates that urinary, rather than tissue, microbial and volatilome signatures show clearer differences between PC and BPH. These findings suggest possible microbiota–metabolite interactions in PC but require validation in larger cohorts. Full article

Polyomaviruses have the potential to cause significant morbidity not only in transplant medicine, but also in other forms of disease or variants of immunosuppression. In kidney transplant recipients or recipients of human stem cell transplants, the BK-Virus is the major proponent of manifestations such as BKPyV-associated nephropathy or hemorrhagic cystitis. As no polyomavirus-specific drug with proven in vivo effects has been developed so far, methods to screen for such drugs are important. This work describes the establishment of a virus-secreting cell line. By infecting a pre-established monkey kidney cell line (COS-1) with a non-rearranged human BK polyomavirus isolated from a kidney transplant patient suffering from BKPyV-associated nephropathy, a continuously replicating cell type with consistent virus secretion could be established and was termed COSSA. Measurements of BKPyV replication, virion production, and secretion were performed both intracellularly and in the cell supernatant. Viral proteins such as VP1 and LTAg were accurately tracked by confocal microscopy, as well as by immunoblot and qPCR. An intracellular flow cytometry (FACS) assay detecting VP1 protein was established and revealed an expanded range of positive intracellular signals. The viruses produced proved to be infectious in human tubular epithelial cell lines. Long-range sequencing of the COSSA genome using Oxford Nanopore Technology revealed a total of five distinct BKPyV integration events. One integration of a partial BKPyV genome was located upstream of the epidermal growth factor receptor gene. The second and third, both truncated forms of integration, were close to histocompatibility gene locuses, while the fourth was characterized by a ninefold and the fifth by a fourfold tandem repeat of the BKPyV genome. From both of the repeat forms, virus replicates were derived showing deletions/duplications on early and late genes and inversions within the non-coding control region (NCCR). This pattern of repetitive viral genome integration is a potential key driver of enhanced viral replication and increased virion assembly, ultimately supporting efficient virus egress. Quantitative PCR analysis confirmed the release of approximately 10⁸/mL viral units per 48 h from 2 × 10⁵ COSSA cells into the culture supernatant. Notably, the NCCR region of the most frequent copies of circular virus and the integrated tetrameric tandem repeat exhibited a rearranged configuration, which may contribute to the observed high replication dynamics. The establishment of a consistent methodology to generate and secrete BKPyV from a cell line is expected to significantly facilitate antiviral drug development. Full article

Esophageal cancer, primarily comprising the squamous cell carcinoma (ESCC) and adenocarcinoma (EAC) subtypes, is the sixth leading cause of cancer deaths globally. In addition to many well-established endogenous and exogenous risk factors, there is emerging evidence for the etiologic role of infectious agents in esophageal cancer, although these associations are incompletely understood. Here, we review the currently available literature on the relationship between infectious agents and esophageal cancer. By far, human papilloma virus (HPV), particularly HPV 16 and 18, have the strongest etiologic association with ESCC. Less robust is the association of high-risk HPV (hr-HPV) with EAC. Although H. pylori has been implicated in the development of EAC via increased acid reflux, decreased lower esophageal sphincter tone, and the resultant Barrett’s metaplasia–dysplasia–adenocarcinoma pathway, some hypothesize based on epidemiological trends that H. pylori may in fact be a protective factor. In rare cases, EBV can cause esophageal lymphoepithelial carcinoma. Several other agents including HSV, polyomaviruses, and Candida are associated with esophageal cancer to varying degrees. In summary, while several studies, including those conflicting with each other, implicate several infectious agents, the evidence is weak, at best. Clearly, further work is needed to help solidify clear etiologies that will help facilitate prevention and treatment. Full article

Approximately 12% of human cancers worldwide are associated with infectious agents, which are classified by the International Agency for Research on Cancer (IARC) as Group 1 within the agents that are carcinogenic to humans. Most of these agents are viruses. Group 1 oncogenic viruses include hepatitis C virus, hepatitis B virus (HBV), human T-cell lymphotropic virus type 1, Epstein-Barr virus, Kaposi sarcoma-associated herpesvirus, human immunodeficiency virus-1 and high-risk human papillomaviruses (HPVs). In addition, some human polyomaviruses are suspected of inducing cancer prevalently in hosts with impaired immune responses. Merkel cell polyomavirus has been associated with Merkel cell carcinoma and included by the IARC in Group 2A (i.e., probably carcinogenic to humans). Linking viruses to human cancers has allowed for the development of diagnostic, prophylactic and therapeutic measures. Vaccination significantly reduced tumours induced by two oncogenic viruses as follows: HBV and HPV. Herein, we focus on mucosal alpha HPVs, which are responsible for the highest number of cancer cases due to tumour viruses and against which effective prevention strategies have been developed to reduce the global burden of HPV-related cancers. Full article

Polyomaviruses are widespread, with BK viruses being most common in humans who require immunosuppression due to allotransplantation. Infection with BK polyomavirus (BKV) may manifest as BK virus-associated nephropathy and hemorrhagic cystitis. Established diagnostic methods include the detection of polyomavirus in urine and blood by PCR and in tissue biopsies via immunohistochemistry. In this study, 79 patients with pathological renal retention parameters and acute kidney injury (AKI) were screened for BK polyomavirus replication by RNA extraction, reverse transcription, and virus-specific qPCR in urine sediment cells. A short fragment of the VP2 coding region was the target of qPCR amplification; patients with (n = 31) and without (n = 48) a history of renal transplantation were included. Urine sediment cell immunofluorescence staining for VP1 BK polyomavirus protein was performed using confocal microscopy. In 22 patients with acute renal injury, urinary sediment cells from 11 participants with kidney transplantation (KTX) and from 11 non-kidney transplanted patients (nonKTX) were positive for BK virus replication. BK virus copies were found more frequently in patients with AKI stage III (n = 14). Higher copy numbers were detected in KTX patients having experienced BK polyoma-nephropathy (BKPyVAN) in the past or diagnosed recently by histology (5.6 × 10⁹–3.1 × 10¹⁰). One patient developed BK viremia following delayed graft function (DGF) with BK virus-positive urine sediment. In nonKTX patients with BK copies, decoy cells were absent; however, positive staining of cells was found with epithelial morphology. Decoy cells were only found in KTX patients with BKPyVAN. In AKI, damage to the tubular epithelium itself may render the epithelial cells more permissive for polyoma replication. This non-invasive diagnostic approach to assess BK polyomavirus replication in urine sediment cells has the potential to identify KTX patients at risk for viremia and BKPyVAN during AKI. This method might serve as a valuable screening tool for close monitoring and tailored immunosuppression decisions. Full article

Protein phosphorylation and dephosphorylation are the most common post-translational modifications mediated by protein kinases and protein phosphatases, respectively. These reversible processes can modulate the function of the target protein, such as its activity, subcellular localization, stability, and interaction with other proteins. Phosphorylation of viral proteins plays an important role in the life cycle of a virus. In this review, we highlight biological implications of the phosphorylation of the monkey polyomavirus SV40 large T and small t antigens, summarize our current knowledge of the phosphorylation of these proteins of human polyomaviruses, and conclude with gaps in the knowledge and a proposal for future research directions. Full article

BK (BKPyV) and JC (JCPyV) polyomaviruses are widespread in humans. Transmission at an early age and the role of parents in spreading these viruses through the family are incompletely understood. Our aim was to determine the seroprevalence of BKPyV and JCPyV in infants at the age of 1, 2, 6, 12, 24, and 36 months and to assess the frequency of BKPyV and JCPyV seroconversion. A variety of maternal and paternal covariates were also tested as potential predictors of these early childhood infections. We used multiplex serology to analyze antibodies to BKPyV and JCPyV from baseline to 3-year follow-up visits. We observed that there was nearly perfect correlation in BKPyV and JCPyV serum IgG antibody levels between the mother-infant pairs during the first year of the infant’s life. No correlation among BKPyV antibody titers were found in father–child pairs, whereas JCPyV antibody levels of the father and child had a significant correlation at the 2-year follow-up visit. BKPyV infection may be associated with a child’s predisposition to allergy. In conclusion, after the decay of maternal antibodies, children start to develop their own immunity toward BKPyV and JCPyV, and horizontal transmission of infection in the family can occur. Full article

The number of identified human polyomaviruses (HPyVs) has increased steadily over the last decade. Some of the novel HPyVs have been shown to cause disease in immunocompromised individuals. The Lyon-IARC polyomavirus (LIPyV) belonging to species Alphapolyomavirus quardecihominis was identified in 2017 in skin and saliva samples from healthy individuals. Since its initial discovery, LIPyV has rarely been detected in human clinical samples but has been detected in faeces from cats with diarrhoea. Serological studies show low LIPyV seroprevalence in human populations. To investigate the possibility that LIPyV is a feline rather than a human polyomavirus, we compared serum IgG responses against the VP1 major capsid protein of LIPyV and 13 other HPyVs among cats (n = 40), dogs (n = 38) and humans (n = 87) using an in-house immunoassay. Seropositivity among cats was very high (92.5%) compared to dogs (31.6%) and humans (2.3%). Furthermore, the median antibody titres against LIPyV were 100–10,000x higher in cats compared to dogs and humans. In conclusion, the high prevalence and intensity of measured seroresponses suggest LIPyV to be a feline rather than a human polyomavirus. Whether LIPyV infection induces diarrhoea or other symptoms in cats remains to be established. Full article

Breast cancer (BC) is the most frequently diagnosed cancer and the leading cause of cancer death in women worldwide, accounting for 24.5% of total new cancer cases and 15.5% of total cancer deaths. Similarly, BC is the most common cancer among Moroccan women, comprising a noteworthy percentage of 40% of all cancers in women. Globally, 15% of cancers are attributable to infections; among them, viruses play a significant role. The present study aimed to explore the presence of a wide range of viral DNA in samples recovered from 76 Moroccan patients with BC and 12 controls using Luminex technology. The explored viruses were as follows: 10 polyomaviruses (PyVs): BKV, KIV, JCV, MCV, WUV, TSV, HPyV6, HPyV7, HPyV9, and SV40; and 5 Herpesviruses (HHVs): CMV, EBV1, EBV2, HSV1, and HSV2. Our results revealed the presence of PyVs DNA in both control (16.7%) and BC tissues (18.4%). Nonetheless, HHV DNA was detected exclusively in BC tissues (23.7%), with a predominance of Epstein–Barr virus (EBV) (21%). In conclusion, our study highlights the presence of EBV in human BC tissues, which may play an important role in its development and/or progression. Further investigations are needed to confirm the presence/co-presence of these viruses in BC. Full article

Polyomaviruses (PyVs) are highly prevalent in humans and animals. PyVs cause mild illness, however, they can also elicit severe diseases. Some PyVs are potentially zoonotic, such as simian virus 40 (SV40). However, data are still lacking about their biology, infectivity, and host interaction with different PyVs. We investigated the immunogenic properties of virus-like particles (VLPs) derived from viral protein 1 (VP1) of human PyVs. We immunised mice with recombinant HPyV VP1 VLPs mimicking the structure of viruses and compared their immunogenicity and cross-reactivity of antisera using a broad spectrum of VP1 VLPs derived from the PyVs of humans and animals. We demonstrated a strong immunogenicity of studied VLPs and a high degree of antigenic similarity between VP1 VLPs of different PyVs. PyV-specific monoclonal antibodies were generated and applied for investigation of VLPs phagocytosis. This study demonstrated that HPyV VLPs are highly immunogenic and interact with phagocytes. Data on the cross-reactivity of VP1 VLP-specific antisera revealed antigenic similarities among VP1 VLPs of particular human and animal PyVs and suggested possible cross-immunity. As the VP1 capsid protein is the major viral antigen involved in virus-host interaction, an approach based on the use of recombinant VLPs is relevant for studying PyV biology regarding PyV interaction with the host immune system. Full article

The polyomaviruses that infect humans, JC virus (JCV) and BK virus (BKV), can establish persistent infections in the cells that make up the renal system, causing nephritis and BKV-associated nephropathy in up to 10% of renal transplant patients, and of these, 90% lose the graft and return for hemodialysis. This study aimed to determine the prevalence of polyomaviruses (PyV) in the population with chronic kidney disease (CKD), classified into three groups (conservative, dialysis, and transplanted) and a control group. Urine samples were collected from 290 individuals, including 202 patients with CKD and 88 from the control group. PyV screening was performed by PCR amplification of a fragment of the VP1 region, and the JCV and BKV species were distinguished through enzymatic digestion with the restriction endonuclease BamHI from the amplification of a TAg region. All amplification products were visualized on a 3% agarose gel. The prevalence of PyV infection was correlated with clinical-epidemiological variables using the chi-squared and Fisher’s exact tests. In the group with CKD, the prevalence of PyV was 30.2%, a higher rate being observed in conservative patients (36.66%; 22/60), followed by dialysis patients (30.48%; 25/82), and transplanted patients (20%; 12/60). In the control group, the prevalence was 46.59% (41/88). The differentiation between species revealed that JCV was present in 77.8% and BKV in 22.2% of the group with CKD. The prevalence of infection was higher in male patients (59.32%), whose most common pathology was systemic arterial hypertension (35.59%). In the group of transplanted patients, there was a statistically significant association between infection and the use of the immunosuppressant azathioprine (p = 0.015). The prevalence of PyV infection was higher in the control group than in the group with CKD, being predominant in males and in patients with systemic arterial hypertension. Full article

Since it was clearly established that HIV/AIDS predisposes to the infection, persistence or reactivation of latent viruses, the prevalence of human polyomaviruses (HPyVs) among HIV-1-infected patients and a possible correlation between HPyVs and HIV sero-status were investigated. PCR was performed to detect and quantify JCPyV, BKPyV, MCPyV, HPyV6, HPyV7 and QPyV DNA in the urine and plasma samples of 103 HIV-1-infected patients. Subsequently, NCCR, VP1 and MCPyV LT sequences were examined. In addition, for MCPyV, the expression of transcripts for the LT gene was investigated. JCPyV, BKPyV and MCPyV’s presence was reported, whereas HPyV6, HPyV7 and QPyV were not detected in any sample. Co-infection patterns of JCPyV, BKPyV and MCPyV were found. Archetype-like NCCRs were observed with some point mutations in plasma samples positive for JCPyV and BKPyV. The VP1 region was found to be highly conserved among these subjects. LT did not show mutations causing stop codons, and LT transcripts were expressed in MCPyV positive samples. A significant correlation between HPyVs’ detection and a low level of CD4+ was reported. In conclusion, HPyV6, HPyV7 and QPyV seem to not have a clinical relevance in HIV-1 patients, whereas further studies are warranted to define the clinical importance of JCPyV, BKPyV and MCPyV DNA detection in these subjects. Full article

Our aim was to study the seroprevalence of human polyomaviruses (HPyV) linked to skin diseases. A total of 552 serum samples were analysed by the enzyme-linked immunosorbent assay to detect IgG antibodies against Merkel cell polyomavirus (MCPyV), HPyV6, HPyV7 and Trichodysplasia spinulosa-associated polyomavirus (TSPyV) using recombinant major capsid proteins of these viruses. The individuals (age 0.8–85 years, median 33) were sorted into seven age groups: <6, 6–10, 10–14, 14–21, 21–40, 40–60 and >60 years. The adulthood seroprevalence was 69.3%, 87.7%, 83.8% and 85% for MCPyV, HPyV6, HPyV7 and TSPyV, respectively. For all four polyomaviruses, there was increasing seropositivity with age until reaching the adulthood level. There was a significant increase in seroreactivity for those age groups in which the rate of already-infected individuals also showed significant differences. The adulthood seropositvity was relatively stable with ageing, except for TSPyV, for which elevated seropositivity was observed for the elderly (>60 years) age group. Since seroepidemiological data have been published with wide ranges for all the viruses studied, we performed a comprehensive analysis comparing the published age-specific seropositivities to our data. Although the cohorts, methods and even the antigens were variable among the studies, there were similar results for all studied polyomaviruses. For MCPyV, geographically distinct genotypes might exist, which might also result in the differences in the seroprevalence data. Additional studies with comparable study groups and methods are required to clarify whether there are geographical differences. Full article

An aetiological role of human papillomavirus (HPV) and/or human polyomaviruses (HPyVs) has been proposed in adenoid cystic carcinoma (AdCC). Moreover, HPV-related multiphenotypic carcinoma (HMSC) was recently introduced as an emerging entity of the sinonasal region. Here, we primarily want to study the role of HPV/HPyV in a large AdCC cohort and, secondly, possibly identify and characterize HMSC. Tumour DNA from 68 patients initially diagnosed with AdCC between 2000 and 2012 was, therefore, tested for 27 HPV types and 10 HPyVs. HPV DNA-positive samples were micromorphologically re-evaluated, further stained for p16^INK4a, S100, p63 and CD117 and tested for the presence of the MYB-NFIB fusion transcript. Notably, no samples were HPyV-positive, while one sinonasal and two tonsillar carcinomas were HPV- and p16-positive. After re-evaluating the micromorphology, immunohistochemistry and presence of fusion transcripts, all tumours had the same appearance and fitted within the diagnosis of HMSC, but in all these three cases, the morphology of the HMSC and basaloid squamous cell carcinoma was overlapping. We conclude that HPV and HPyV have no major role in AdCC. However, based on our data, we also suggest that HMSC should be considered as a basaloid variant of squamous cell carcinoma, and not its own entity, until better characterized. Full article

To date, 14 human polyomaviruses (HPyVs) have been identified using high-throughput technologies. Among them, MCPyV, HPyV6, HPyV7 and TSPyV present a skin tropism, but a causal role in skin diseases has been established only for MCPyV as a causative agent of Merkel cell carcinoma (MCC) and TSPyV as an etiological agent of Trichodysplasia Spinulosa (TS). In the search for a possible role for cutaneous HPyVs in the development of skin malignant lesions, we investigated the prevalence of MCPyV, HPyV6, HPyV7 and TSPyV in actinic keratosis (AK), a premalignant skin lesion that has the potential to progress towards a squamous cell carcinoma (SCC). One skin lesion and one non-lesion skin from nine affected individuals were analyzed by qualitative PCR. MCPyV was detected in 9 out of 9 lesion biopsies and 6 out of 8 non-lesion biopsies. HPyV6 was detected only in healthy skin, while HPyV7 and TSPyV were not detected in any skin sample. These findings argue against a possible role of cutaneous HPyVs in AK. However, considering the small sample size analyzed, a definitive conclusion cannot be drawn. Longitudinal studies on large cohorts are warranted. Full article