Serology Identifies LIPyV as a Feline Rather than a Human Polyomavirus.

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.

Logic-gated antibody pairs that selectively act on cells co-expressing two antigens.

The use of therapeutic monoclonal antibodies is constrained because single antigen targets often do not provide sufficient selectivity to distinguish diseased from healthy tissues. We present HexElect®, an approach to enhance the functional selectivity of therapeutic antibodies by making their activity dependent on clustering after binding to two different antigens expressed on the same target cell. lmmunoglobulin G (lgG)-mediated clustering of membrane receptors naturally occurs on cell surfaces to trigger complement- or cell-mediated effector functions or to initiate intracellular signaling. We engineer the Fc domains of two different lgG antibodies to suppress their individual homo-oligomerization while promoting their pairwise hetero-oligomerization after binding co-expressed antigens. We show that recruitment of complement component C1q to these hetero-oligomers leads to clustering-dependent activation of effector functions such as complement mediated killing of target cells or activation of cell surface receptors. HexElect allows selective antibody activity on target cells expressing unique, potentially unexplored combinations of surface antigens.

Translating genomic exploration of the family Polyomaviridae into confident human polyomavirus detection.

The Polyomaviridae is a family of ubiquitous dsDNA viruses that establish persistent infection early in life. Screening for human polyomaviruses (HPyVs), which comprise 14 diverse species, relies upon species-specific qPCRs whose validity may be challenged by accelerating genomic exploration of the virosphere. Using this reasoning, we tested 64 published HPyV qPCR assays in silico against the 1781 PyV genome sequences that were divided in targets and nontargets, based on anticipated species specificity of each qPCR. We identified several cases of problematic qPCR performance that were confirmed in vitro and corrected through using degenerate oligos. Furthermore, our study ranked 8 out of 52 tested BKPyV qPCRs as remaining of consistently high quality in the wake of recent PyV discoveries and showed how sensitivity of most other qPCRs could be rescued by annealing temperature adjustment. This study establishes an efficient framework for ensuring confidence in available HPyV qPCRs in the genomic era.

Prevalence of DNA of fourteen human polyomaviruses determined in blood donors.

BACKGROUND: Human polyomaviruses (HPyVs), like herpesviruses, cause persistent infection in a large part of the population. In immunocompromised and elderly patients, PyVs cause severe diseases such as nephropathy (BK polyomavirus [BKPyV]), progressive multifocal leukoencephalopathy (JC polyomavirus [JCPyV]), and skin cancer (Merkel cell polyomavirus [MCPyV]). Like cytomegalovirus, donor-derived PyV can cause disease in kidney transplant recipients. Possibly blood components transmit PyVs as well. To study this possibility, as a first step we determined the presence of PyV DNA in Dutch blood donations. STUDY DESIGN AND METHODS: Blood donor serum samples (n = 1016) were analyzed for the presence of DNA of 14 HPyVs using HPyV species-specific quantitative polymerase chain reaction (PCR) procedures. PCR-positive samples were subjected to confirmation by sequencing. Individual PCR findings were compared with the previously reported PyV serostatus. RESULTS: MC polyomavirus DNA was detected in 39 donors (3.8%), JCPyV and TS polyomavirus (TSPyV) DNA in five donors (both 0.5%), and HPyV9 DNA in four donors (0.4%). BKPyV, WU polyomavirus (WUPyV), HPyV6, MW polyomavirus (MWPyV), and LI polyomavirus (LIPyV) DNA was detected in one or two donors. Amplicon sequencing confirmed the expected product for BKPyV, JCPyV, WUPyV, MCPyV, HPyV6, TSPyV, MWPyV, HPyV9, and LIPyV. For JCPyV a significant association was observed between detection of viral DNA and the level of specific IgG antibodies. CONCLUSION: In 5.4% of Dutch blood donors PyV DNA was detected, including DNA from pathogenic PyVs such as JCPyV. As a next step, the infectivity of PyV in donor blood and transmission via blood components to immunocompromised recipients should be investigated.

Primary trichodysplasia spinulosa polyomavirus infection in a kidney transplant child displaying virus-infected decoy cells in the urine.

We report a case of primary trichodysplasia spinulosa (TS) infection in a kidney transplant child and describe for the first time the presence of degenerated TS-associated polyomavirus (TSPyV)-infected cells in a TS patient's urine that are morphologically different from BK or JC polyomavirus-infected decoy cells.

Impact of HPyV9 and TSPyV coinfection on the development of BK polyomavirus viremia and associated nephropathy after kidney transplantation.

BACKGROUND: BK polyomavirus (BKPyV) persistently infects the urinary tract and causes viremia and nephropathy in kidney transplantation (KTx), recipients. In a previous study, we observed an increased incidence and load of BKPyV viremia in KTx patients coinfected with human polyomavirus 9 (HPyV9). Here we sought confirmation of this observation and explored whether novel HPyVs that have been detected in urine (HPyV9 and trichodysplasia spinulosa polyomavirus [TSPyV]) potentially aggravate BKPyV infection. METHODS: A well-characterized cohort of 209 KTx donor-recipient pairs was serologically and molecularly analyzed for HPyV9 and TSPyV coinfection. These data were correlated with the occurrence of BKPyV viremia and BKPyVAN in the recipients within a year after KTx. RESULTS: Seropositivity for HPyV9 (19%) and TSPyV (89%) was comparable between donors and recipients and did not correlate with BKPyV viremia and BKPyVAN that developed in 25% and 3% of the recipients, respectively. Two recipients developed TSPyV viremia and none HPyV9 viremia. Modification of the predictive effect of donor BKPyV seroreactivity on recipient BKPyV viremia by HPyV9 and TSPyV was not observed. CONCLUSIONS: Our data provide no evidence for a promoting effect of HPyV9 and TSPyV on BKPyV infection and BKPyVAN in renal allograft patients. Therefore, we do not recommend including HPyV9 and TSPyV screening in KTx patients.

Development and evaluation of a BK polyomavirus serotyping assay using Luminex technology.

BACKGROUND: The BK polyomavirus (BKPyV) is subdivided into four genotypes. The consequences of each genotype and of donor-recipient genotype (mis)match for BKPyV-associated nephropathy (BKPyVAN) in kidney transplant recipients (KTRs) are unknown. OBJECTIVES: To develop and evaluate a genotype-specific IgG antibody-based BKPyV serotyping assay, in order to classify kidney transplant donors and recipients accordingly. STUDY DESIGN: VP1 antigens of six BKPyV variants (Ib1, Ib2, Ic, II, III and IV) were expressed as recombinant glutathione-s-transferase-fusion proteins and coupled to fluorescent Luminex beads. Sera from 87 healthy blood donors and 39 KTRs were used to analyze seroreactivity and serospecificity against the different BKPyV genotypes. Six sera with marked BKPyV serotype profiles were analyzed further for genotype-specific BKPyV pseudovirus neutralizing capacity. RESULTS: Seroreactivity was observed against all genotypes, with seropositivity rates above 77% comparable for KTRs and blood donors. Strong cross-reactivity (r > 0.8) was observed among genotype I subtypes, and among genotypes II, III and IV. Seroresponses against genotypes I and IV seemed genuine, while those against II and III could be out(cross)competed. GMT (Luminex) and IC50 (neutralization assay) values showed good agreement in determining the genotype with the strongest seroresponse within an individual. CONCLUSIONS: Despite some degree of cross-reactivity, this serotyping assay seems a useful tool to identify the main infecting BKPyV genotype within a given individual. This information, which cannot be obtained otherwise from nonviremic/nonviruric individuals, could provide valuable information regarding the prevalent BKPyV genotype in kidney donors and recipients and warrants further study.

Seroprevalence of fourteen human polyomaviruses determined in blood donors.

The polyomavirus family currently includes thirteen human polyomavirus (HPyV) species. In immunocompromised and elderly persons HPyVs are known to cause disease, such as progressive multifocal leukoencephalopathy (JCPyV), haemorrhagic cystitis and nephropathy (BKPyV), Merkel cell carcinoma (MCPyV), and trichodysplasia spinulosa (TSPyV). Some recently discovered polyomaviruses are of still unknown prevalence and pathogenic potential. Because HPyVs infections persist and might be transferred by blood components to immunocompromised patients, we studied the seroprevalence of fourteen polyomaviruses in adult Dutch blood donors. For most polyomaviruses the observed seroprevalence was high (60-100%), sometimes slightly increasing or decreasing with age. Seroreactivity increased with age for JCPyV, HPyV6 and HPyV7 and decreased for BKPyV and TSPyV. The most recently identified polyomaviruses HPyV12, NJPyV and LIPyV showed low overall seroprevalence (~5%) and low seroreactivity, questioning their human tropism. Altogether, HPyV infections are common in Dutch blood donors, with an average of nine polyomaviruses per subject.

The Human Polyomavirus Middle and Alternative T-Antigens; Thoughts on Roles and Relevance to Cancer.

Approximately 15-20% of human cancer is related to infection, which renders them potentially preventable by antimicrobial or antiviral therapy. Human polyomaviruses (PyVs) are relevant in this regard, as illustrated by the involvement of Merkel cell polyomavirus (MCPyV) in the development of Merkel cell carcinoma. The polyomavirus Small and Large tumor antigen (ST and LT) have been extensively studied with respect to their role in oncogenesis. Recently it was shown that a number of human PyVs, including MCPyV and the trichodysplasia spinulosa polyomavirus (TSPyV), express additional T-antigens called Middle T (MT) and alternative T (ALT). ALT is encoded by ORF5, also known as the alternative T open reading frame (ALTO), which also encodes the second exon of MT, and overlaps out-of-frame with the second exon of LT. Previously, MT was considered unique for oncogenic rodent polyomaviruses, and ALT was still unknown. In this mini-review, we want to point out there are important reasons to explore the involvement of MT and ALT in human cellular transformation. First, just like their rodent equivalents, MT and ALT probably disrupt cellular pathways that control signaling and proliferation. Second, expression of the MT and ALT-encoding ORF5/ALTO characterizes a monophyletic polyomavirus clade that includes human and animal PyVs with known oncogenic potential. And third, ORF5/ALTO is subject to strong positive selection aimed specifically at a short linear motif within MT and ALT that overlaps completely with the RB-binding motif in LT. The latter suggests tight interplay between these T-antigens with possible consequences for cell transformation.

Development and Evaluation of a Broad Bead-Based Multiplex Immunoassay To Measure IgG Seroreactivity against Human Polyomaviruses.

The family of polyomaviruses, which cause severe disease in immunocompromised hosts, has expanded substantially in recent years. To accommodate measurement of IgG seroresponses against all currently known human polyomaviruses (HPyVs), including the Lyon IARC polyomavirus (LIPyV), we extended our custom multiplex bead-based HPyV immunoassay and evaluated the performance of this pan-HPyV immunoassay. The VP1 proteins of 15 HPyVs belonging to 13 Polyomavirus species were expressed as recombinant glutathione S-transferase (GST) fusion proteins and coupled to fluorescent Luminex beads. Sera from healthy blood donors and immunocompromised kidney transplant recipients were used to analyze seroreactivity against the different HPyVs. For BK polyomavirus (BKPyV), the GST-VP1 fusion protein-directed seroresponses were compared to those obtained against BKPyV VP1 virus-like particles (VLP). Seroreactivity against most HPyVs was common and generally high in both test populations. Low seroreactivity against HPyV9, HPyV12, New Jersey PyV, and LIPyV was observed. The assay was reproducible (Pearson's r2 > 0.84, P < 0.001) and specific. Weak but consistent cross-reactivity between the related viruses HPyV6 and HPyV7 was observed. The seroresponses measured by the GST-VP1-based immunoassay and a VP1 VLP-based enzyme-linked immunosorbent assay were highly correlated (Spearman's ρ = 0.823, P < 0.001). The bead-based pan-HPyV multiplex immunoassay is a reliable tool to determine HPyV-specific seroresponses with high reproducibility and specificity and is suitable for use in seroepidemiological studies.

Stability of BK polyomavirus IgG seroreactivity and its correlation with preceding viremia.

BACKGROUND: Recently we showed that the level of BK polyomavirus (BKPyV) IgG seroreactivity in kidney donors predicted viremia and BKPyV-associated nephropathy in kidney transplant recipients (KTRs). This observation could be explained by assuming a direct association between BKPyV seroreactivity and the amount of persistent infectious virus in the renal allograft. OBJECTIVES: Since the renal BKPyV reservoir is probably sowed by viremia during primary BKPyV infection, we systematically analysed the dynamics of BKPyV IgG seroreactivity in relation to preceding BKPyV viremia in KTRs and healthy individuals. STUDY DESIGN: A cohort of 85 KTRs consisting of BKPyV viremic and nonviremic subjects was analysed for BKPyV IgG seroreactivity at five fixed time points until one year after transplantation. A cohort of 87 healthy blood donors (HBDs) was used as controls. RESULTS: Baseline BKPyV seropositivity was high in both KTRs and HBDs, and the baseline mean BKPyV IgG level comparable. BKPyV IgG levels in nonviremic KTRs and HBDs remained stable during follow-up, while a considerable increase was observed in viremic KTRs (p=0.015). The increase of BKPyV seroreactivity in viremic KTRs was associated with the duration and peak level of BKPyV viremia. CONCLUSIONS: BKPyV IgG seroreactivity was stable over time in immunocompetent subjects, which enables the use of this potential pretransplantation biomarker in kidney donors. The observed dose-dependent relationship of BKPyV IgG seroreactivity with preceding BKPyV replication is in agreement with the assumption that BKPyV seroreactivity reflects past BKPyV activity and correlates with the amount of latent BKPyV residing within a kidney allograft.

Primary Polyomavirus Infection, Not Reactivation, as the Cause of Trichodysplasia Spinulosa in Immunocompromised Patients.

Classic human polyomaviruses (JC and BK viruses) become pathogenic when reactivating from latency. For the rare skin disease trichodysplasia spinulosa, we show that manifestations of the causative polyomavirus (TSPyV) occur during primary infection of the immunosuppressed host. High TSPyV loads in blood and cerebrospinal fluid, sometimes coinciding with cerebral lesions and neuroendocrine symptoms, marked the acute phase of trichodysplasia spinulosa, whereas initiation and maturation of TSPyV seroresponses occurred in the convalescent phase. TSPyV genomes lacked the rearrangements typical for reactivating polyomaviruses. These findings demonstrate the clinical importance of primary infection with this rapidly expanding group of human viruses and explain the rarity of some novel polyomavirus-associated diseases.

Limited variation during circulation of a polyomavirus in the human population involves the COCO-VA toggling site of Middle and Alternative T-antigen(s).

We have recently shown that the trichodysplasia spinulosa-associated polyomavirus (TSPyV) belongs to a large monophyletic group of mammalian polyomaviruses that experienced accelerated codon-constrained Val-Ala (COCO-VA) toggling at a protein site common to both Middle and Alternative T-antigens (MT/ALTO). Here we analyzed thirteen, mostly newly sequenced TSPyV genomes, representing ~40% of reported TS disease cases world-wide. We found two deletions and 30 variable sites (≤0.6%) that included only four sites with non-synonymous substitutions (NSS). One NSS site was under positive selection in the exon shared by Small and Middle T antigens, while three others were segregated in MT/ALTO. Two MT/ALTO sites covaried with five sites elsewhere in the genome and determined separation of twelve TSPyVs into two most populous phylogenetic lineages. The other, most distant TSPyV was distinguished by NSS at the COCO-VA site, observed for the first time during intra-species evolution. Our findings reveal a connection between micro- and macro-evolution of polyomaviruses.

Characterization of T Antigens, Including Middle T and Alternative T, Expressed by the Human Polyomavirus Associated with Trichodysplasia Spinulosa.

UNLABELLED: The polyomavirus tumor (T) antigens play crucial roles in viral replication, transcription, and cellular transformation. They are encoded by partially overlapping open reading frames (ORFs) located in the early region through alternative mRNA splicing. The T expression pattern of the trichodysplasia spinulosa-associated polyomavirus (TSPyV) has not been established yet, hampering further study of its pathogenic mechanisms and taxonomic relationship. Here, we characterized TSPyV T antigen expression in human cell lines transfected with the TSPyV early region. Sequencing of T antigen-encoded reverse transcription-PCR (RT-PCR) products revealed three splice donor and acceptor sites creating six mRNA splice products that potentially encode the antigens small T (ST), middle T (MT), large T (LT), tiny T, 21kT, and alternative T (ALTO). Except for 21kT, these splice products were also detected in skin of TSPyV-infected patients. At least three splice products were confirmed by Northern blotting, likely encoding LT, MT, ST, 21kT, and ALTO. Protein expression was demonstrated for LT, ALTO, and possibly MT, with LT detected in the nucleus and ALTO in the cytoplasm of transfected cells. Splice site and start codon mutations indicated that ALTO is encoded by the same splice product that encodes LT and uses internal start codons for initiation. The genuineness of ALTO was indicated by the identification of acetylated N-terminal ALTO peptides by mass spectrometry. Summarizing, TSPyV exhibits an expression pattern characterized by both MT and ALTO expression, combining features of rodent and human polyomaviruses. This unique expression pattern provides important leads for further study of polyomavirus-related disease and for an understanding of polyomavirus evolution. IMPORTANCE: The human trichodysplasia spinulosa-associated polyomavirus (TSPyV) is distinguished among polyomaviruses for combining productive infection with cell-transforming properties. In the research presented here, we further substantiate this unique position by indicating expression of both middle T antigen (MT) and alternative T antigen (ALTO) in TSPyV. So far, none of the human polyomaviruses was shown to express MT, which is considered the most important viral oncoprotein of rodent polyomaviruses. Coexpression of ALTO and MT, which involves a conserved, recently recognized overlapping ORF subject to positive selection, has not been observed before for any polyomavirus. As a result of our findings, this study provides valuable new insights into polyomavirus T gene use and expression. Obviously, these insights will be instrumental in further study and gaining an understanding of TSPyV pathogenicity. More importantly, however, they provide important leads with regard to the interrelationship, functionality, and evolution of polyomaviruses as a whole, indicating that TSPyV is a suitable model virus to study these entities further.

The presence of betapapillomavirus antibodies around transplantation predicts the development of keratinocyte carcinoma in organ transplant recipients: a cohort study.

Organ transplant recipients (OTRs) have an increased risk of developing keratinocyte carcinomas (KCs). The aim of this study was to correlate infection with human papillomaviruses (HPVs) belonging to the beta genus (Beta-papillomavirus (Beta-PV)) at transplantation with later development of KCs. In a cohort study, sera collected between 1 year before and 1 year after transplantation of OTRs transplanted between 1990 and 2006 were tested for antibody responses against the L1 capsid antigen of Beta-PV and other HPV genera (Gamma-, Mu-, Nu-, and Alpha-PV) using multiplex serology. The OTRs were followed for a maximum of 22 years. Cox regression models with KC, squamous cell carcinoma (SCC), and basal cell carcinoma (BCC) as outcome variables were used. Out of 445 OTRs, 60 had developed KC: 14 developed only SCC, 24 only BCC, and 22 both types of KC. The time-dependent hazard ratio (HR) to develop either or both types of KC, adjusted for age, sex, and transplanted organ, in tested Beta-PV-seropositive OTR around the time of transplantation compared with Beta-PV-seronegative OTR was 2.9 (95% confidence interval (CI) 1.3-6.4). The HR for SCC was 2.9 (95% CI 0.99-8.5) and for BCC it was 3.1 (95% CI 1.2-8.0). There was also an association between Mu-PV seropositivity and KC, but there were no significant associations between other HPV genera tested and KC. A positive seroresponse for Beta-PV around transplantation significantly predicted the development of KC in OTRs up to 22 years later, providing additional evidence that infection with Beta-PV has a role in KC carcinogenesis.

Polyomavirus-associated Trichodysplasia spinulosa involves hyperproliferation, pRB phosphorylation and upregulation of p16 and p21.

Trichodysplasia spinulosa (TS) is a proliferative skin disease observed in severely immunocompromized patients. It is characterized by papule and trichohyalin-rich spicule formation, epidermal acanthosis and distention of dysmorphic hair follicles overpopulated by inner root sheath cells (IRS). TS probably results from active infection with the TS-associated polyomavirus (TSPyV), as indicated by high viral-load, virus protein expression and particle formation. The underlying pathogenic mechanism imposed by TSPyV infection has not been solved yet. By analogy with other polyomaviruses, such as the Merkel cell polyomavirus associated with Merkel cell carcinoma, we hypothesized that TSPyV T-antigen promotes proliferation of infected IRS cells. Therefore, we analyzed TS biopsy sections for markers of cell proliferation (Ki-67) and cell cycle regulation (p16ink4a, p21waf, pRB, phosphorylated pRB), and the putatively transforming TSPyV early large tumor (LT) antigen. Intense Ki-67 staining was detected especially in the margins of TS hair follicles, which colocalized with TSPyV LT-antigen detection. In this area, staining was also noted for pRB and particularly phosphorylated pRB, as well as p16ink4a and p21waf. Healthy control hair follicles did not or hardly stained for these markers. Trichohyalin was particularly detected in the center of TS follicles that stained negative for Ki-67 and TSPyV LT-antigen. In summary, we provide evidence for clustering of TSPyV LT-antigen-expressing and proliferating cells in the follicle margins that overproduce negative cell cycle regulatory proteins. These data are compatible with a scenario of TSPyV T-antigen-mediated cell cycle progression, potentially creating a pool of proliferating cells that enable viral DNA replication and drive papule and spicule formation.

Human polyomavirus 9 infection in kidney transplant patients.

Several human polyomaviruses of unknown prevalence and pathogenicity have been identified, including human polyomavirus 9 (HPyV9). To determine rates of HPyV9 infection among immunosuppressed patients, we screened serum samples from 101 kidney transplant patients in the Netherlands for HPyV9 DNA and seroreactivity. A total of 21 patients had positive results for HPyV9 DNA; positivity rates peaked at 3 months after transplantation, but the highest viral loads were measured just after transplantation. During 18 months of follow-up, HPyV9 seroprevalence increased from 33% to 46% among transplant patients; seroprevalence remained stable at ≈30% in a control group of healthy blood donors in whom no HPyV9 DNA was detected. Further analysis revealed an association between detection of HPyV9 and detection of BK polyomavirus but not of cytomegalovirus. Our data indicate that HPyV9 infection is frequent in kidney transplant patients, but the nature of infection-endogenous or donor-derived-and pathogenic potential of this virus remain unknown.

Different serologic behavior of MCPyV, TSPyV, HPyV6, HPyV7 and HPyV9 polyomaviruses found on the skin.

The polyomavirus family is rapidly expanding with twelve new human viruses identified since 2007. A significant number of the new human polyomaviruses (HPyV) has been found on the skin. Whether these viruses share biological properties and should be grouped together is unknown. Here we investigated the serological behavior of cutaneous HPyVs in a general population. 799 sera from immunocompetent Australian individuals aged between 0-87 were analyzed with a Luminex xMAP technology-based immunoassay for the presence of VP1-directed IgG antibodies against MCPyV, HPyV6, HPyV7, TSPyV, HPyV9, and BKPyV as a control. Except for HPyV9, overall seropositivity was high for the cutanous polyomaviruses (66-81% in adults), and gradually increased with age. Children below 6 months displayed seropositivity rates comparable to the adults, indicative of maternal antibodies. TSPyV seroreactivity levels strongly increased after age 2 and waned later in life comparable to BKPyV, whereas MCPyV, HPyV6 and HPyV7 seroreactivity remained rather stable throughout. Based on the identified serologic profiles, MCPyV seems to cluster with HPyV6 and HPyV7, and TSPyV and HPyV9 by themselves. These profiles indicate heterogeneity among cutaneous polyomaviruses and probably reflect differences in exposure and pathogenic behavior of these viruses.

The trichodysplasia spinulosa-associated polyomavirus: virological background and clinical implications.

Trichodysplasia spinulosa-associated polyomavirus (TSPyV) is a new species of the family Polyomaviridae that was discovered in 2010. TSPyV infects humans and is associated with the development of a rare disease called trichodysplasia spinulosa. Trichodysplasia spinulosa is a skin disease of severely immunocompromised hosts characterized by follicular distention and keratotic spine formation especially on the face. Electron microscopy, immunohistochemistry, and viral load measurements indicate an etiological role of active TSPyV infection in the development of this disease. This review will address virological and pathogenic properties of TSPyV, as well as epidemiologic, diagnostic, and therapeutic aspects of TSPyV infection.

From Stockholm to Malawi: recent developments in studying human polyomaviruses.

Until a few years ago the polyomavirus family (Polyomaviridae) included a dozen viruses identified in avian and mammalian hosts. Two of these, the JC and BK-polyomaviruses isolated a long time ago, are known to infect humans and cause severe illness in immunocompromised hosts. Since 2007 an unprecedented number of eight novel polyomaviruses were discovered in humans. Among them are the KI- and WU-polyomaviruses identified in respiratory samples, the Merkel cell polyomavirus found in skin carcinomas and the polyomavirus associated with trichodysplasia spinulosa, a skin disease of transplant patients. Another four novel human polyomaviruses were identified, HPyV6, HPyV7, HPyV9 and the Malawi polyomavirus, so far not associated with any disease. In the same period several novel mammalian polyomaviruses were described. This review summarizes the recent developments in studying the novel human polyomaviruses, and touches upon several aspects of polyomavirus virology, pathogenicity, epidemiology and phylogeny.