Human Polyomaviruses (HPyVs) in Human Diseases and Cancer Development

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Animal Viruses".

Deadline for manuscript submissions: closed (30 November 2022) | Viewed by 22943

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Guest Editor
Department of Public Health and Infectious Diseases, “Sapienza” University, 00185 Rome, Italy
Interests: human polyomaviruses; Merkel cell polyomavirus; oncogenesis; microRNAs; DNA damage response
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Guest Editor
Department of Public Health and Infectious Diseases, “Sapienza” University, Rome, Italy
Interests: polyomaviridae family; polyomavirus-associated diseases in humans; evaluation of predictive biomarkers to manage polyomavirus infection and reativation in immunodepressed patients or in patients treated with different disease-modifying therapies; study of the polyomaviruses’s contribution into the development of cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

To date, fifteen polyomavirus (PyVs) have been isolated from humans (HPyVs); among these, only six HPyVs are firmly associated with diseases. BKPyV can cause nephropathy and hemorrhagic cystitis, JCPyV is the causative agent of progressive multifocal leukoencephalopathy (PML), TSPyV is linked to the rare skin disease trichodysplasia spinulosa (TS), and HPyV6 and HPyV7 are associated with pruritic rash. Presently, MCPyV is the only HPyV proven to cause cancer in its host, named Merkel cell carcinomas (MCC). Although HPyVs other than MCPyV share many common features, including the viral oncoproteins large tumor antigen (LT-ag) and small tumor antigen (sT-ag), their role in cancer is questionable. Specifically, BKPyV and JCPyV have been suspected to be involved in renal, prostate, colon, and brain cancer, but convincing evidence is still lacking, as well as for HPyV6 and HPyV7.

The viral genome copy number and possible integration in tumors may also indicate whether or not HPyVs are involved in cancer. Immunodeficiency of the host may enhance the activity of HPyVs and hence contribute. Consequently, HPyVs may play a contributing role in immunocompromised patients who develop cancer.

To continue to enrich knowledge about HPyVs research, we would like to invite you to share your recent findings or perspectives and future directions on: polyomavirus-associated diseases in humans, the mechanism of viral persistence and the conditions that lead to viral reactivation upon immunosuppression, the role that host immunity plays in controlling HPyVs infection, the debated oncogenic role of HPyVs in cancer development, viral oncogenesis, pathogenesis, and new experimental models.

Dr. Valeria Pietropaolo
Dr. Carla Prezioso
Guest Editors

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Keywords

  • HPyVs-associated disease
  • HPyVs-associated cancers
  • viral oncogenesis
  • large tumor antigen (LT-ag) and small tumor antigen (sT-ag)
  • viral persistence and reactivation
  • host immunity
  • cells and animal models

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Published Papers (8 papers)

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Research

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10 pages, 2090 KiB  
Communication
Serology Identifies LIPyV as a Feline Rather than a Human Polyomavirus
by Sergio Kamminga, Els van der Meijden, Patricia Pesavento, Christopher B. Buck and Mariet C. W. Feltkamp
Viruses 2023, 15(7), 1546; https://doi.org/10.3390/v15071546 - 13 Jul 2023
Cited by 2 | Viewed by 1265
Abstract
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 [...] Read more.
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
(This article belongs to the Special Issue Human Polyomaviruses (HPyVs) in Human Diseases and Cancer Development)
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16 pages, 3068 KiB  
Article
Co-Detection of EBV and Human Polyomavirus JCPyV in a Case of AIDS-Related Multifocal Primary Central Nervous System Diffuse Large B-Cell Lymphoma
by Mallory T. Barbier and Luis Del Valle
Viruses 2023, 15(3), 755; https://doi.org/10.3390/v15030755 - 15 Mar 2023
Cited by 1 | Viewed by 2219
Abstract
The human neurotropic Polyomavirus JCPyV is the widespread opportunistic causative pathogen of the fatal demyelinating disease progressive multifocal leukoencephalopathy; however, it has also been implicated in the oncogenesis of several types of cancers. It causes brain tumors when intracerebrally inoculated into rodents, and [...] Read more.
The human neurotropic Polyomavirus JCPyV is the widespread opportunistic causative pathogen of the fatal demyelinating disease progressive multifocal leukoencephalopathy; however, it has also been implicated in the oncogenesis of several types of cancers. It causes brain tumors when intracerebrally inoculated into rodents, and genomic sequences of different strains and expression of the viral protein large T-Antigen have been detected in a wide variety of glial brain tumors and CNS lymphomas. Here, we present a case of an AIDS-related multifocal primary CNS lymphoma in which JCPyV genomic sequences of the three regions of JCPyV and expression of T-Antigen were detected by PCR and immunohistochemistry, respectively. No capsid proteins were detected, ruling out active JCPyV replication. Sequencing of the control region revealed that Mad-4 was the strain of JCPyV present in tumor cells. In addition, expression of viral proteins LMP and EBNA-1 from another ubiquitous oncogenic virus, Epstein–Barr, was also detected in the same lymphocytic neoplastic cells, co-localizing with JCPyV T-Antigen, suggesting a potential collaboration between these two viruses in the process of malignant transformation of B-lymphocytes, which are the site of latency and reactivation for both viruses. Full article
(This article belongs to the Special Issue Human Polyomaviruses (HPyVs) in Human Diseases and Cancer Development)
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16 pages, 348 KiB  
Article
Detection Analysis and Study of Genomic Region Variability of JCPyV, BKPyV, MCPyV, HPyV6, HPyV7 and QPyV in the Urine and Plasma of HIV-1-Infected Patients
by Sara Passerini, Carla Prezioso, Annalisa Prota, Giulia Babini, Luigi Coppola, Alessandra Lodi, Anna Chiara Epifani, Loredana Sarmati, Massimo Andreoni, Ugo Moens, Valeria Pietropaolo and Marco Ciotti
Viruses 2022, 14(11), 2544; https://doi.org/10.3390/v14112544 - 17 Nov 2022
Cited by 3 | Viewed by 1533
Abstract
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 [...] Read more.
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
(This article belongs to the Special Issue Human Polyomaviruses (HPyVs) in Human Diseases and Cancer Development)
15 pages, 2192 KiB  
Article
Quantification of APOBEC3 Mutation Rates Affecting the VP1 Gene of BK Polyomavirus In Vivo
by Dorian McIlroy, Cécile Peltier, My-Linh Nguyen, Louise Manceau, Lenha Mobuchon, Nicolas Le Baut, Ngoc-Khanh Nguyen, Minh-Chau Tran, The-Cuong Nguyen and Céline Bressollette-Bodin
Viruses 2022, 14(9), 2077; https://doi.org/10.3390/v14092077 - 19 Sep 2022
Cited by 4 | Viewed by 2240
Abstract
Mutations in the BK polyomavirus (BKPyV) capsid accumulate in kidney transplant (KTx) recipients with persistent virus replication. They are associated with neutralization escape and appear to arise as a result of cytosine deamination by host cell APOBEC3A/B enzymes. To study the mutagenic processes [...] Read more.
Mutations in the BK polyomavirus (BKPyV) capsid accumulate in kidney transplant (KTx) recipients with persistent virus replication. They are associated with neutralization escape and appear to arise as a result of cytosine deamination by host cell APOBEC3A/B enzymes. To study the mutagenic processes occurring in patients, we amplified the typing region of the VP1 gene, sequenced the amplicons to a depth of 5000–10,000×, and identified rare mutations, which were fitted to COSMIC mutational signatures. Background mutations were identified in amplicons from plasmids carrying the BKPyV genome and compared to mutations observed in 148 samples from 23 KTx recipients in France and in Vietnam. Three mutational signatures were consistently observed in urine, serum, and kidney biopsy samples, two of which, SBS2 and SBS13, corresponded to APOBEC3A/B activity. In addition, a third signature with no known etiology, SBS89, was detected both in patient samples, and in cells infected in vitro with BKPyV. Quantitatively, APOBEC3A/B mutation rates in urine samples were strongly correlated with urine viral load, and also appeared to vary between individuals. These results confirm that APOBEC3A/B is a major, but not the only, source of BKPyV genome mutations in patients. Full article
(This article belongs to the Special Issue Human Polyomaviruses (HPyVs) in Human Diseases and Cancer Development)
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7 pages, 1344 KiB  
Communication
Prevalence of MCPyV, HPyV6, HPyV7 and TSPyV in Actinic Keratosis Biopsy Specimens
by Carla Prezioso, Gabriele Brazzini, Sara Passerini, Carlotta Di Fabio, Terenzio Cosio, Sergio Bernardini, Elena Campione, Ugo Moens, Valeria Pietropaolo and Marco Ciotti
Viruses 2022, 14(2), 427; https://doi.org/10.3390/v14020427 - 18 Feb 2022
Cited by 1 | Viewed by 1860
Abstract
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 [...] Read more.
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
(This article belongs to the Special Issue Human Polyomaviruses (HPyVs) in Human Diseases and Cancer Development)
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16 pages, 1500 KiB  
Article
Molecular Epidemiology and Variation of the BK Polyomavirus in the Population of Central and Eastern Europe Based on the Example of Poland
by Jacek Furmaga, Marek Kowalczyk, Olga Furmaga, Christos A. Rokos, Tomasz Zapolski, Leszek Krakowski, Andrzej Jakubczak and Sławomir Rudzki
Viruses 2022, 14(2), 209; https://doi.org/10.3390/v14020209 - 21 Jan 2022
Cited by 10 | Viewed by 2993
Abstract
The BK polyomavirus (BKPyV) is a widespread pathogen in humans. Polymorphism of the region encoding the VP1 protein of BKPyV provides the basis for classifying the virus into types and subtypes, whose frequency varies depending on geographic location. The aim of our study [...] Read more.
The BK polyomavirus (BKPyV) is a widespread pathogen in humans. Polymorphism of the region encoding the VP1 protein of BKPyV provides the basis for classifying the virus into types and subtypes, whose frequency varies depending on geographic location. The aim of our study was to determine the frequency of BKPyV in the Polish population and to assess its variation by analysing polymorphism in the typing region. The study was conducted on 168 healthy, Polish volunteers, whose blood (plasma) and urine were sampled. The virus was detected using PCR, products, sequenced and subjected to bioinformatic analysis. In addition, viral load was assessed by qPCR. The presence of the genetic material of the BK virus was noted in 61/168 urine samples but in none of the plasma sample. Sequencing and phylogenetic analysis confirmed that the BKPyV isolates were of types I and IV, dominant in Europe (63.93% and 36.07%, respectively). All isolates from genotype I belonged to subtype Ib-2, showing polymorphism at position 1809 with a frequency of 61.54% (G1809A) and 38.46% (G1809C). To the best of our knowledge, this is the first study of this magnitude on the genetic variation of BKPyV among healthy volunteers in Poland. Full article
(This article belongs to the Special Issue Human Polyomaviruses (HPyVs) in Human Diseases and Cancer Development)
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Review

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18 pages, 2509 KiB  
Review
BK Virus Nephropathy in Kidney Transplantation: A State-of-the-Art Review
by Sam Kant, Alana Dasgupta, Serena Bagnasco and Daniel C. Brennan
Viruses 2022, 14(8), 1616; https://doi.org/10.3390/v14081616 - 25 Jul 2022
Cited by 34 | Viewed by 7566
Abstract
BK virus maintains a latent infection that is ubiquitous in humans. It has a propensity for reactivation in the setting of a dysfunctional cellular immune response and is frequently encountered in kidney transplant recipients. Screening for the virus has been effective in preventing [...] Read more.
BK virus maintains a latent infection that is ubiquitous in humans. It has a propensity for reactivation in the setting of a dysfunctional cellular immune response and is frequently encountered in kidney transplant recipients. Screening for the virus has been effective in preventing progression to nephropathy and graft loss. However, it can be a diagnostic and therapeutic challenge. In this in-depth state-of-the-art review, we will discuss the history of the virus, virology, epidemiology, cellular response, pathogenesis, methods of screening and diagnosis, evidence-based treatment strategies, and upcoming therapeutics, along with the issue of re-transplantation in patients. Full article
(This article belongs to the Special Issue Human Polyomaviruses (HPyVs) in Human Diseases and Cancer Development)
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Other

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7 pages, 1106 KiB  
Brief Report
Comparison of Quantitative Real-Time PCR and Digital PCR to Detect the Polyomavirus in Merkel Cell Carcinoma
by Martina Barchitta, Andrea Maugeri, Elisabetta Campisi, Roberta Magnano San Lio, Giuliana Favara, Hector Jose Soto Parra, Lucia Salvatorelli, Gaetano Magro, Guido Basile and Antonella Agodi
Viruses 2022, 14(10), 2195; https://doi.org/10.3390/v14102195 - 5 Oct 2022
Cited by 4 | Viewed by 1956
Abstract
Merkel cell polyomavirus (MCPyV) prevalence in Merkel cell carcinoma (MCC) cases is controversial. The detection and quantification of MCPyV DNA is mainly performed by PCR techniques using formalin-fixed, paraffin-embedded (FFPE) tissues. The aim of this study is to compare the performance of two [...] Read more.
Merkel cell polyomavirus (MCPyV) prevalence in Merkel cell carcinoma (MCC) cases is controversial. The detection and quantification of MCPyV DNA is mainly performed by PCR techniques using formalin-fixed, paraffin-embedded (FFPE) tissues. The aim of this study is to compare the performance of two different molecular techniques, specifically the quantitative Real-Time PCR (qPCR) and digital PCR (dPCR). Samples from 31 cases of MCC excisional surgical biopsies were analyzed. DNA extraction and purification from clinical samples were performed using the QIAcube Qiagen automated nucleic acid extractor. After the extraction, MCPyV was detected by qPCR and dPCR using specially designed primers and probes. Of the 31 MCC samples under study, the MCPyV genome was detected in 11 samples (35%) by qPCR compared with 20 samples (65%) detected by dPCR. Notably, 65% of primary tumors were positive for MCPyV (15/23). The viral genome was detected in 75% of tumors located at UV-exposed sites (6/8), 55% of tumors at partially UV-protected sites (5/9), and 67% of tumors at UV-protected sites (4/6). Our results showed a better sensitivity of dPCR in detecting the MCPyV genome in MCC samples compared with traditional qPCR techniques. Full article
(This article belongs to the Special Issue Human Polyomaviruses (HPyVs) in Human Diseases and Cancer Development)
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