Skip to main content
NCBI home page
NIHPA Author Manuscripts logoLink to NIHPA Author Manuscripts
. Author manuscript; available in PMC: 2020 Feb 1.
Published in final edited form as: J Invest Dermatol. 2018 Nov 22;139(2):285–292. doi: 10.1016/j.jid.2018.09.013

The Biology and Clinical Features of Cutaneous Polyomaviruses

Khang D Nguyen 1, Bahir H Chamseddin 1, Clay J Cockerell 1, Richard C Wang 1
PMCID: PMC6500491  NIHMSID: NIHMS1010410  PMID: 30470393

Abstract

Human polyomaviruses are dsDNA viruses with a conserved genomic structure, yet they present with diverse tissue tropisms and disease presentations. Merkel Cell Polyomavirus (MCPyV), Trichodysplasia Spinulosa Polyomavirus (TSPyV), Human Polyomavirus 6 (HPyV6), Human Polyomavirus 7 (HPyV7), and Malawi Polyomavirus (MWPyV) are shed from the skin, and MCPyV, TSPyV, HPyV6, and HPyV7 have been linked to specific skin diseases. We present an update on the genomic and clinical features of these cutaneous polyomaviruses.

The identification and study of human polyomaviruses (PyVs) has expanded dramatically in the past decade. The BK and JC polyomaviruses were first human polyomaviruses discovered and linked to nephropathy and progressive multifocal leukoencephalopathy in 1971 (Gardner :et al., 1971; Padgett et al., 1971). Since 2007, starting with KI and WU polyomaviruses, improved technologies have uncovered 10 more possible human polyomaviruses (Allander et al., 2007; Gaynor et al., 2007; Kamminga et al., 2018). Here, we discuss the polyomaviruses shed from human skin, with a particular focus on those linked to disease, including trichodysplasia spinulosa polyomavirus (TSPyV), human polyomavirus 6 (HPyV6), and human polyomavirus 7 (HPyV7).

Genomic Structure

Although the overall genomic structure is conserved between cutaneous polyomaviruses, some subtle differences exist (Table 1). Like canonical polyomaviruses, cutaneous polyomaviruses all possess genomes of ~5,000 bp. The polyomavirus genome is divided into early, late, and non-coding control (NCCR) regions. All cutaneous polyomavirus early regions encode for Large and Small T antigens (LT and ST, respectively).

Table 1.

Genomic Features of Cutaneous Polyomaviruses

Polyomavirus Reference genome Size (bp) LT (AA) ST (AA) MT (AA) ALTO (AA) VP1/2/3 (AA) MicroRNA Cell Receptor
MCPyV NC_010277.2 5387 817 186 - 248/250 423/241/196 Present Ganglioside GT1b/glycosaminoglycans
TSPyV NC_014361.1 5232 697 198 332 131 376/313/195 - GM1/sialylactose
HPyV6 NC_14406.1 4926 669 190 - - 387/336/215 - ND (non-ganglioside)
HPyV7 NC_14407.1 4952 671 193 - - 380/329/290 - ND (non-ganglioside)
MWPyV (HPyV10) NC_018102.1 4927 668 199 - - 404/31½01 - ND
Open in a new tab

-, no evidence for presence

ND, not determined

Early region transcription occurs first, before viral DNA replication. LT alone can replicate the polyomavirus genome. Domains essential for DNA replication are conserved in all cutaneous polyomaviruses, including the DnaJ domain (HPDKGG), Rb/p107/p130 binding motif (LXCXE), Zinc-binding (Zn-binding) motif, helicase, and nuclear localization sequence (Table 2) (Borchert et al., 2014; DeCaprio and Garcea, 2013; Van Ghelue et al., 2012). The LXCXE and DnaJ/Hsc70 binding motifs work together to bind Rb and disrupt its interaction with E2F to promote cell cycle progression and viral replication (Sullivan et al., 2000). The Zn-binding motif and helicase domains allow LT to oligomerize and bind viral DNA, unwind it, and recruit host cell DNA replication factors (Zhou et al., 2012). Some polyomaviruses also use the helicase domain to bind and inhibit the p53 tumor suppressor. While HPyV6/7 and MWPyV LT’s bind directly to p53 (Berrios et al., 2015; Rozenblatt-Rosen et al., 2012), MCPyV LT inhibits p53 signaling without a direct interaction (Borchert et al., 2014; Cheng et al., 2013). TSPyV LT has also been shown to lack significant interaction with p53 (An et al., 2015). Non-conserved domains in LT show differences between the cutaneous polyomaviruses (Table 2) (Van Ghelue et al., 2012). MCPyV LT is slightly larger due to an uncharacterized insertion between the DnaJ- and Rb-binding motifs. The LT’s of TSPyV, HPyV6/7, and MWPyV, but not MCPyV, possess a motif (WXXWW), which binds the spindle checkpoint protein Bub1. This domain is required for the transforming, but not the immortalizing, properties of SV40 LT (Cotsiki et al., 2004). SV40 LT also promotes transformation through a CUL7-binding motif (FNXEX) in its N-terminus, which is only conserved in TSPyV (Ali et al., 2004).

Table 2.

Locations of Large T and Small T Motifs and Ligands.

Large T Small T
Motif DnaJ WXXWW CUL7 LXCXE NLS OBD Zinc Finger p53 binding LSD Zinc Finger
Ligand Hsc70 Bub1 CUL7 Rb,p107,p130 KPNA DNA DNA p53 Fbxw7 PP2A subunits
Sequence HPDKGG WXXWW FNXEX LXCXE KRK undefined CX2X7HX3H undefined LKDYM C(1XX)->H(1XX)
MCPyV 42–47 -§ -§ 212–216 299–307 316–430 473–488 -⊺ 92–96 109–130
TSPyV 42–47 99–103 106–110 122–126 174–182 191–306 (NVE) 350–365 - 93–97§ 113–132
HPyV6 42–47 93–97 -§ 109–113 139–147 154–273 (NVE) 317–330 +* - 111–130§
HPyV7 42–47 94–98 -§ 109–113 144–152 159–278 (NVE) 322–335 +* - 111–130§
MWPyV 42–47 90–94 -§ 105–109 149–157 163–280 (NVE) 324–339 +* - 110–130§
SV40 42–47 91–95 98–102 103–107 124–132 139–256 302–317 351–450, 533–626 - 102–122
Open in a new tab

NLS, Nuclear Localizing Sequence

OBD, Origin Binding Domain

LSD, LT Stabilization Domain

-, no evidence for presence

ND, not determined

§,

not verified experimentally

⊺ -

indirect binding to p53

* -

direct binding to p53

The small T antigen (ST) is generated through alternative splicing and shares the LT DnaJ domain. The C terminal half of ST possesses two conserved Zn-binding motifs that bind to PP2A isoforms promoting viral DNA replication through multiple mechanisms. The PP2A-binding region of SV40 ST promotes cell cycle progression (Schuchner and Wintersberger, 1999) and inhibits LT degradation (Scheidtmann et al., 1991), but these activities have not been tested in cutaneous ST’s. The PP2A binding regions appear to be conserved amongst cutaneous polyomaviruses (Table 2). MCPyV ST stabilizes LT through a distinct LSD motif that is conserved in TSPyV, but not in HPyV6/7 or MWPyV (Table 2) (Kwun et al., 2013). While MCPyV ST can transform primary fibroblasts (Shuda et al., 2011), the transforming properties of other cutaneous ST’s is unknown.

Some PyV’s possess an alternative open reading frame overlapping with LT that encodes for additional protein(s). The TSPyV early region encodes for both middle T antigen (MT) and alternative T antigen (ALTO) (Carter et al., 2013; van der Meijden et al., 2015); the MCPyV early region only encodes for ALTO (van der Meijden et al., 2015) while HPyV6/7 and MWPyV encode for neither (Table 1). While the well characterized Mouse Polyomavirus MT is a phosphorylated membrane protein that alters signaling pathways and promotes transformation, the functions of MT/ALTO of cutaneous PyV’s require further characterization (van der Meijden and Feltkamp, 2018).

MCPyV is the only cutaneous PyV known to encode for a microRNA (Table 1). Like SV40, MCPyV’s microRNA is inhibits LT expression, possibly as a means to limit replication and promote episomal persistence (Seo et al., 2009). More recent reports also suggest that the MCPyV’s microRNA may also attenuate the host immune response (Akhbari et al., 2018).

The polyomavirus late genes encode for the capsomere proteins, which surround the viral genome and promote attachment and entry into host cells. Many polyomavirus capsids bind gangliosides terminating in sialic acid as their primary attachment receptor through a structurally conserved groove (Stehle et al., 1994). While MCPyV can bind to ganglioside GT1b (Erickson et al., 2009), glycosaminoglycans have been implicated as the primary entry receptor (Table 1) (Schowalter et al., 2012). More recent structural studies have also demonstrated that the proposed sialic acid binding site is occluded in HPyV6/7, suggesting alternative receptors for cutaneous PyV’s (Stroh et al., 2014).

Merkel Cell Polyomavirus

MCPyV and its associated disease, Merkel Cell Carcinoma, have been extensively reviewed elsewhere. Serological studies indicate that exposure to MCPyV is widespread (DeCaprio, 2017; van der Meijden et al., 2011). Viral DNA is present in 2.6% of healthy blood donors (Mazzoni et al., 2017). Primary exposure to MCPyV begins in childhood after a period of immunity from maternal antibodies (Martel-Jantin et al., 2013; Nicol et al., 2013). Seroprevalence rates rise from early childhood until adulthood, in which 60–96.2% of adult populations are estimated to have had MCPyV exposure (Martel-Jantin et al., 2013; Nicol et al., 2013)). MCPyV appears to be the cutaneous polyomavirus most frequently shed from the skin with studies suggesting shedding from up to 61.5% of healthy individuals (Hampras et al., 2015; Schowalter et al., 2010). An increasing body of research has strongly implicated MCPyV as a cause of its associated carcinoma (DeCaprio, 2017; Feng et al., 2008). Links between MCPyV and other inflammatory or malignant skin conditions remain unconfirmed.

Trichodysplasia Spinulosa Polyomavirus

Case reports in the early 2000s identified a facial, folliculocentric eruption and alopecia in immunosuppressed patients first described as “pilomatrix dysplasia” and later “cyclosporine-induced folliculodystrophy” (Chastain and Millikan, 2000; Haycox et al., 1999; Heaphy et al., 2004; Sperling et al., 2004). While some reports implicated cyclosporine, electron microscopy suggested a viral etiology (Haycox et al., 1999; Sperling et al., 2004). In 2010, van der Meijden and colleagues identified the causative virus, trichodysplasia spinulosa polyomavirus (TSPyV) in the disease (van der Meijden et al., 2010). TSPyV viral loads average ~106 copies per cell in lesional skin samples as compared to <102 copies per cell in non-lesional and healthy control skin samples (Kazem 2012).

Children are often born with maternal antibodies to TSPyV, but begin producing their own antibodies in the first year after primary exposure (Chen et al., 2011; Fukumoto et al., 2015; van der Meijden et al., 2013). Transmission may occur through family members, possibly through respiratory secretions (Bialasiewicz et al., 2017; Pedergnana et al., 2017). Adult seroprevalence ranges from 63.2% to 81% (Chen et al., 2011; Nicol et al., 2013; Sroller et al., 2016; van der Meijden et al., 2013; van der Meijden et al., 2011). Skin infection appears to be transient, as skin swabs shows low prevalence of viral DNA (0–3.8% in adults) (Hampras et al., 2015; Schowalter et al., 2010; Wieland et al., 2014).

TS patients have numerous, mildly pruritic, folliculocentric, flesh-colored to pink papules with central keratinaceous spines (Fig. 1a) (Haycox et al., 1999; Matthews et al., 2011; Sperling et al., 2004; van der Meijden et al., 2010). Alopecia favoring the eyebrows and sometimes skin thickening creating a leonine facies, may occur concomitantly (van der Meijden et al., 2010). All cases have been associated with iatrogenic immunosuppressive medications including cyclosporine, prednisone, mycophenolate, azathioprine, methotrexate, tacrolimus, and numerous chemotherapies (Aleissa et al., 2017; Matthews et al., 2011). There is recent evidence that TS may result from a primary infection rather than viral reactivation (Bialasiewicz et al., 2017; van der Meijden et al., 2017).

Figure 1. Clinical and Histologic Features of Human Polyomavirus Infections.

Figure 1.

Open in a new tab

(a) In trichodysplasia spinulosa, patients present with folliculocentric, flesh-colored and pink papules with complete eyebrow alopecia. Though not seen here, keratinaceous spines may protrude from the center of the papules. (b) These hair follicles are dilated and filled with dystrophic material. The hair shaft is malformed. Enlarged cells with increased trichohyaline granules are present in the inner root sheath (IRS) epithelium (left, scale bar = 500 μm). Expansion of the IRS epithelium is frequently noted (right, scale = 200 μm). (c) HPyV6/7 associated pruritic and dyskeratotic dermatitis (H6PD/H7PD) presents as gray-brown, lichenified plaques on the trunk and extremities. These changes were visible on the trunk and upper extremities in this patient’s posterior deltoid (left) and back (right). Images reproduced with permission from (Smith et al., 2018). (d) Histology shows epidermal papillomatosis and irregular columns of parakeratosis (left, scale bar = 100 μm). Dyskeratotic keratinocytes and irregular columns of parakeratosis are visible at higher magnification (right, scale bar = 50 μm). Histologic images courtesy of Dr. Peter Pavlidakey.

Histology reveals distended anagen hair follicles with dilated infundibula that are plugged with refractile, dystrophic material (Fig. 1b) (Haycox et al., 1999; Matthews et al., 2011; Sperling et al., 2004; van der Meijden et al., 2010). Hair shafts are poorly formed or absent (Haycox et al., 1999; van der Meijden et al., 2010). An expanded inner root sheath epithelium contains enlarged cells with increased trichohyaline granules and increased apoptotic cells (Fig 1c) (Haycox et al., 1999; Leitenberger et al., 2015; Sperling et al., 2004).

In the skin, TSPyV infects the inner root sheath keratinocytes (Fischer et al., 2012; Rouanet et al., 2016) (Wanat et al., 2012). The virus has also been identified in the blood, cerebrospinal fluid, respiratory tract, urinary tract, feces, cardiac tissue, and renal allografts, suggesting it may be a systemic infection (Fischer et al., 2012; Rockett et al., 2013; Tsuzuki et al., 2014; Urbano et al., 2016; van der Meijden et al., 2017). Despite its broad tissue distribution, TSPyV has not been linked to other diseases (Fava et al., 2016; Toptan et al., 2016).

Successful treatments for TS have only been reported for a handful of patients. Clearance with cautious reduction in immunosuppressive therapies has been reported (Coogle et al., 2017; van der Meijden et al., 2017). Topical antiviral medicines (e.g. cidofovir 1% or 3%) and physical measures (e.g. plucking and shaving) have been successful (Aleissa et al., 2017; Barton et al., 2017; Benoit et al., 2010; Campbell et al., 2006; Coogle et al., 2017; Leitenberger et al., 2015; Santesteban et al., 2015; van der Meijden et al., 2017; Wanat et al., 2012). Treatment with oral valgancyclovir, acitretin, and leflunomide has also been reported (Aleissa et al., 2017; Kassar et al., 2017). There have been some reports of success using combinations of the aforementioned therapies, such as the reduction of immunosuppression combined with topical or oral therapies (Coogle et al., 2017; van der Meijden et al., 2017) and the combination oral acitretin and oral valganciclovir (Aleissa et al., 2017).

Human Polyomaviruses 6 and 7

Rolling-circle amplification of human skin swabs identified the closely related human polyomavirus 6 (HPyV6) and human polyomavirus 7 (HPyV7) from the skin of healthy volunteers (Schowalter et al., 2010). Like MCPyV, their detection in healthy volunteers suggested the ability of these viruses to be shed through latent or subclinical infections. While most newborns are seropositive (~80% for HPyV6, ~60% for HPyV7), seropositivity fell after the first 6 months of life, then rose with older cohorts, consistent with HPyV6/7 infection early in life for most individuals (Nicol et al., 2013; van der Meijden et al., 2013). Adult seroprevalences are 69%−83% for HPyV6 and 35%−66% for HPyV7 in populations throughout the world (Gossai et al., 2016b; Nicol et al., 2013; Schowalter et al., 2010; Sroller et al., 2016; van der Meijden et al., 2013). Examination of skin swabs revealed the presence of HPyV6 in 12–27.6% samples and HPyV7 2.1–13.4% (Hampras et al., 2015; Hashida et al., 2017; Schowalter et al., 2010; Wieland et al., 2014). Higher levels were detected in an HIV positive population (39% for HPyV6 and 21% for HPyV7) (Wieland et al., 2014). Persistence of viral DNA shedding over 6 months in the majority of individuals further support chronic skin infection and asymptomatic shedding in a portion of individuals infected with HPyV6 and HPyV7 (Hashida et al., 2017).

The constellation of clinical findings of HPyV6/7 infection have been referred to as “HPyV6- and HPyV7-associated pruritic and dyskeratotic dermatoses” (H6PD or H7PD), “human polyomavirus-7-associated rash and pruritus”, and “HPyV-associated hyperproliferative keratinopathy plus/minus pruritus” (Canavan et al., 2017; Ho et al., 2014; Nguyen et al., 2017; Smith et al., 2018). Cutaneous HPyV6 and HPyV7 infection manifests with pruritic, brown to gray, lichenified plaques involving the trunk and extremities (Fig. 1c). (Canavan et al., 2017; Ho et al., 2014; Nguyen et al., 2017; Smith et al., 2018). With the exception of one case occurring in a patient immunosuppressed from human immunodeficiency virus infection ((Nguyen et al., 2017), published cases have been associated with cardiac and lung transplants (Canavan et al., 2017, Ho et al., 2014, Smith et al., 2018). Immunosuppressive medicines in these organ transplant recipients included prednisone, azathioprine, sirolimus, tacrolimus, everolimus, and mycophenolate (Canavan et al., 2017, Ho et al., 2014, Smith et al., 2018). Histopathology reveals epidermal papillomatosis, dyskeratotic keratinocytes in the epidermis, and irregular columns of parakeratosis, the latter referred to as “peacock plumage,” “columnar dyskeratosis,” or “tiered parakeratosis with dyskeratosis” (Fig. 1d) (Canavan et al., 2018; Champagne et al., 2015; Ho et al., 2014; Nguyen et al., 2017; Pock and Stork, 2010). In the upper dermis, there may be sparse, perivascular, lymphocytic infiltrates (Ho et al., 2014; Pock and Stork, 2010). Viral T antigen and capsid proteins have been identified within keratinocytes, strongly suggesting that keratinocytes are the principal cell infected by HPyV7 in these dermatoses (Ho et al., 2014; Nguyen et al., 2017). Compared to healthy, control, skin samples, viral loads in lesional skin samples are several orders of magnitude higher (~1.44–2.37 × 106 copies/LINE repeat vs ~3.11 × 101 copies/LINE repeat for HPyV6, ~2.90 × 103 copies/LINE repeat vs ~1.43 × 101 copies/LINE repeat for HPyV7; 7.28–32.27 X 102 copies/cell vs 0–0.4 copies/cell for HPyV7) (Nguyen et al., 2017, Ho et al., 2015). HPyV6 has been linked to keratoacanthomas, BRAF inhibitor-associated epithelial neoplasms, and Kimura disease (Beckervordersandforth et al., 2016; Rascovan et al., 2016; Schrama et al., 2014). However, other research has refuted the link between HPyV6/HPyV7 and other skin diseases, including both neoplastic and inflammatory skin diseases (Bergallo et al., 2018; Fava et al., 2016; Frouin et al., 2014; Haeggblom et al., 2017; Schrama et al., 2012; Scola et al., 2012).

Like MCPyV and TSPyV, HPyV6 and HPyV7 have also been identified in other tissues. HPyV6 has been detected in tonsillar tissue, cerebrospinal fluid, human bile, the respiratory tract, and feces, while HPyV7 has been noted in tonsillar tissue, human thymic epithelial tumors, urine, the respiratory tract, and feces (Chan et al., 2017; Delbue et al., 2015; Franzen et al., 2016; Rennspiess et al., 2015; Rockett et al., 2013; Salakova et al., 2016; Zheng et al., 2015). No link has been found between HPyV6/7 and internal malignancy (Toptan et al., 2016).

Treatments for infections linked to HPyV6 and HPyV7 remain anecdotal. Specifically, topical and intravenous cidofovir have been successful in isolated cases of HPyV7 infection, likely through its inhibition of viral replication (Canavan et al., 2017; Smith et al., 2018). There are contradictory reports on the benefit of acitretin: one patient had complete resolution of his eruption with acitretin and another patient had no response (Canavan et al., 2017; Smith et al., 2018). Of note, the patient with complete resolution received acitretin 25 mg twice daily, while the non-responder patient received 25 mg once daily, leaving open the possibility that the dose and frequency of treatment may impact the efficacy. No reports have investigated the use of cidofovir or acitretin for HPyV6 infection.

Malawi Polyomvirus (Human Polyomavirus 10)

Malawi Polyomavirus (MWPyV) was discovered in the stool from a healthy child in Malawi after pyrosequencing of purified virus-like particles (Siebrasse et al., 2012). A nearly identical species, HPyV10, was independently identified through rolling-circle amplification of virions prepared from condyloma on the buttock of a patient with warts, hypogammglobulinemia, infections, and myelokathexis (WHIM) syndrome (Buck et al., 2012). Follow-up studies have confirmed the presence of MWPyV/HPyV10 in the stool of both healthy individuals and those with acute diarrheal illness (Yu et al., 2012). The seroprevalence of MWPyV/HPyV10 is very high with estimates of 42–99% in adults (Gossai et al., 2016a; Nicol et al., 2014). Skin swabs detected the virus in 3.4% of healthy individuals and 9.3% of HIV infected men (Wieland et al., 2014). Although MWPyV/HPyV10 DNA is most frequently detected in stool, it is also present in the skin and respiratory samples from symptomatic children (Rockett et al., 2013). Given these findings, it remains unclear whether the bona fide tissue tropism of this virus is the skin or whether it represents a superficial contamination of the epidermis from another tissue source, like the gastrointestinal or respiratory tracts.

Conclusion

In contrast to the hundreds of species of papillomaviruses, there appears to be a smaller cohort of polyomaviruses (10–15) that infects humans. Seroprevalence studies have revealed that many of the more recently discovered polyomaviruses appear to be zoonotic (Kamminga et al., 2018) perhaps suggesting that the discovery of HPyV’s is nearing saturation. Five HPyV’s are shed chronically from human skin at varying levels. Recent work has linked TSPyV to a folliculocentric eruption; HPyV6 and HPyV7 to diffuse, hyperproliferative, pruritic eruptions; and MCPyV to a deadly skin cancer. MWPyV has not yet been linked to any diseases. Despite similarities in their overall genomic structures, subtle differences in both the early and late regions of these cutaneous polyomaviruses in concert with interactions with the host tissues allow the viruses to have distinct tissue tropism and clinical manifestations.

Serological studies have revealed that cutaneous polyomavirus infections occur in most individuals, yet, even among immunosuppressed patients, PyV-mediated diseases are exceedingly rare. Additional studies are necessary to identify the PyV- and host-specific factors that drive the development of clinically relevant infections in rare individuals. Hopefully, these studies will also yield better treatments for the patients who develop these rare, but serious infections. Additional studies will reveal whether cutaneous PyVs contribute to currently idiopathic inflammatory skin conditions or exacerbate common skin diseases. These studies will also reveal whether cutaneous PyVs play commensal or even beneficial roles as members of the skin microbiome. Finally, consistent with the groundbreaking studies of SV40, the continued study of cutaneous PyVs will likely continue to contribute to our understanding of human tumorigenesis.

Table 3.

Seroprevalence, Skin Prevalence, and Disease Associations of Cutaneous Polyomaviruses

Polyomavirus Seroprevalence in Adults DNA Prevalence on Adult Skin Disease Associations
MCPyV 60–96% (Gossai et al., 2016a; Martel-Jantin et al., 2013; Nicol et al., 2013) 40–61.5% (Hampras et al., 2015; Schowalter et al., 2010) Merkel Cell Carcinoma (Feng et al., 2008; Kassem et al., 2008; Moshiri et al., 2017)
Chronic Lymphocytic Leukemia (Pantulu et al., 2010)
TSPyV 63–81% (Chen et al., 2011; Nicol et al., 2013; Sroller et al., 2016; van der Meijden et al., 2011) 0–3.8% (Hampras et al., 2015; Schowalter et al., 2010; Wieland et al., 2014) Trichodysplasia Spinulosa (Kazem et al., 2012; Kazem et al., 2014; Matthews et al., 2011; van der Meijden et al., 2010)
HPyV6 69–88% (Sroller et al., 2016) 12–27.6% (Hampras et al., 2015; Schowalter et al., 2010; Wieland et al., 2014) Human Polyomavirus 6 Associated Pruritic and Dyskeratotic Dermatitis (H6PD) (Nguyen et al., 2017)
BRAF inhibitor-associated epithelial neoplasm (Schrama et al., 2014)
Keratoacanthomas (Beckervordersandforth et al., 2016)
Angiolymphoid Hyperplasia with Eosinophilia (Rascovan et al., 2016)
HPyV7 35–66% (Sroller et al., 2016) 2.1–13.4% (Schowalter et al., 2010; Wieland et al., 2014) Human Polyomavirus 7 Associated Pruritic and Dyskeratotic Dermatitis (H7PD) (Canavan et al., 2017; Ho et al., 2014; Nguyen et al., 2017; Smith et al., 2018)
Human Thymic Epithelial Tumors (Rennspiess et al., 2015)
MWPyV (HPyV10) 42–99% (Gossai et al., 2016a; Nicol et al., 2014) 3.4–9.3% (Wieland et al., 2014) None
Open in a new tab

Acknowledgements

We thank the Wang lab for helpful discussions. Dr. Peter Pavlidakey is thanked for the histologic images of HPyV7 infection. R.W. is supported by a NIAMS 1R01AR072655, a Burroughs Wellcome Fund CAMS (1010978), and American Cancer Society Research Scholar Award (RSG-18-058-01).

Abbreviations

(HPyV)

Human Polyomavirus

(PyV)

Polyomavirus

(MCPyV)

Merkel Cell Polyomavirus

(TSPyV)

Trichodysplasia Spinulosa Polyomavirus

(HPyV6)

Human Polyomavirus 6

(HPyV7)

Human Polyomavirus 7

(MWPyV)

Malawi Polyomavirus

(HPyV10)

Human Polyomavirus 10

(LT)

Large T antigen

(ST)

Small T antigen

(MT)

Middle T antigen

(ALTO)

Alternative T antigen

Footnotes

Conflicts of Interest

The authors declare no conflicts of interest.

References

  1. Akhbari P, Tobin D, Poterlowicz K, Roberts W, Boyne JR. MCV-miR-M1 Targets the Host-Cell Immune Response Resulting in the Attenuation of Neutrophil Chemotaxis. J Invest Dermatol 2018. [DOI] [PubMed] [Google Scholar]
  2. Aleissa M, Konstantinou MP, Samimi M, Lamant L, Gaboriaud P, Touzé A, et al. Trichodysplasia spinulosa associated with HIV infection: clinical response to acitretin and valganciclovir. Clinical and Experimental Dermatology 2017;38:420–3. [DOI] [PubMed] [Google Scholar]
  3. Ali SH, Kasper JS, Arai T, DeCaprio JA. Cul7/p185/p193 binding to simian virus 40 large T antigen has a role in cellular transformation. J Virol 2004;78(6):2749–57. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Allander T, Andreasson K, Gupta S, Bjerkner A, Bogdanovic G, Persson MA, et al. Identification of a third human polyomavirus. J Virol 2007;81(8):4130–6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. An P, Brodsky JL, Pipas JM. The conserved core enzymatic activities and the distinct dynamics of polyomavirus large T antigens. Arch Biochem Biophys 2015;573:23–31. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Barton M, Lockhart S, Sidbury R, Wang R, Brandling-Bennett H. Trichodysplasia Spinulosa in a 7-Year-Old Boy Managed Using Physical Extraction of Keratin Spicules. Pediatric Dermatology 2017;34(2):e74–e6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Beckervordersandforth J, Pujari S, Rennspiess D, Speel EJ, Winnepenninckx V, Diaz C, et al. Frequent detection of human polyomavirus 6 in keratoacanthomas. Diagn Pathol 2016;11(1):58. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Benoit T, Bacelieri R, Morrell DS, Metcalf J. Viral-associated trichodysplasia of immunosuppression: report of a pediatric patient with response to oral valganciclovir. Arch Dermatol 2010;146(8):871–4. [DOI] [PubMed] [Google Scholar]
  9. Bergallo M, Dapra V, Fava P, Ponti R, Calvi C, Montanari P, et al. DNA from Human Polyomaviruses, MWPyV, HPyV6, HPyV7, HPyV9 and HPyV12 in Cutaneous T-cell Lymphomas. Anticancer Res 2018;38(7):4111–4. [DOI] [PubMed] [Google Scholar]
  10. Berrios C, Jung J, Primi B, Wang M, Pedamallu C, Duke F, et al. Malawi polyomavirus is a prevalent human virus that interacts with known tumor suppressors. J Virol 2015;89(1):857–62. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Bialasiewicz S, Byrom L, Fraser C, Clark J. Potential Route of Transmission for Trichodysplasia Spinulosa Polyomavirus. The Journal of infectious diseases 2017;215(7):1175–6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Borchert S, Czech-Sioli M, Neumann F, Schmidt C, Wimmer P, Dobner T, et al. High-affinity Rb binding, p53 inhibition, subcellular localization, and transformation by wild-type or tumor-derived shortened Merkel cell polyomavirus large T antigens. J Virol 2014;88(6):3144–60. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Buck CB, Phan GQ, Raiji MT, Murphy PM, McDermott DH, McBride AA. Complete genome sequence of a tenth human polyomavirus. J Virol 2012;86(19):10887. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Campbell RM, Ney A, Gohh R, Robinson-Bostom L. Spiny hyperkeratotic projections on the face and extremities of a kidney transplant recipient. Arch Dermatol 2006;142(12):1643–8. [DOI] [PubMed] [Google Scholar]
  15. Canavan TN, Baddley JW, Pavlidakey P, Tallaj JA, Elewski BE. Human polyomavirus-7-associated eruption successfully treated with acitretin. American Journal of Transplantation 2017;161(6):1739–7. [DOI] [PubMed] [Google Scholar]
  16. Canavan TN, Baddley JW, Pavlidakey P, Tallaj JA, Elewski BE. Human polyomavirus-7-associated eruption successfully treated with acitretin. Am J Transplant 2018;18(5):1278–84. [DOI] [PubMed] [Google Scholar]
  17. Carter JJ, Daugherty MD, Qi X, Bheda-Malge A, Wipf GC, Robinson K, et al. Identification of an overprinting gene in Merkel cell polyomavirus provides evolutionary insight into the birth of viral genes. Proc Natl Acad Sci U S A 2013;110(31):12744–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Champagne C, Moore L, Reule R, Dyer JA, Rady P, Tyring SK, et al. Cornoid Lamella-Like Structures in HIV-Associated Epidermodysplasia Verruciformis: A Unique Histopathologic Finding. Am J Dermatopathol 2015;37(12):929–32. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Chan JFW, Tee K-M, Choi GKY, Zhu Z, Poon RWS, Ng KTP, et al. First detection and complete genome sequence of a phylogenetically distinct human polyomavirus 6 highly prevalent in human bile samples. The Journal of infection 2017;74(1):50–9. [DOI] [PubMed] [Google Scholar]
  20. Chastain MA, Millikan LE. Pilomatrix dysplasia in an immunosuppressed patient. J Am Acad Dermatol 2000;43(1 Pt 1):118–22. [DOI] [PubMed] [Google Scholar]
  21. Chen T, Mattila PS, Jartti T, Ruuskanen O, Soderlund-Venermo M, Hedman K. Seroepidemiology of the newly found trichodysplasia spinulosa-associated polyomavirus. J Infect Dis 2011;204(10):1523–6. [DOI] [PubMed] [Google Scholar]
  22. Cheng J, Rozenblatt-Rosen O, Paulson KG, Nghiem P, DeCaprio JA. Merkel cell polyomavirus large T antigen has growth-promoting and inhibitory activities. J Virol 2013;87(11):6118–26. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Coogle LP, Holland KE, Pan C, Van Why SK. Complete resolution of trichodysplasia spinulosa in a pediatric renal transplant patient: Case report and literature review. Pediatric Transplantation 2017;21(2):e12849–5. [DOI] [PubMed] [Google Scholar]
  24. Cotsiki M, Lock RL, Cheng Y, Williams GL, Zhao J, Perera D, et al. Simian virus 40 large T antigen targets the spindle assembly checkpoint protein Bub1. Proc Natl Acad Sci U S A 2004;101(4):947–52. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. DeCaprio JA. Merkel cell polyomavirus and Merkel cell carcinoma. Philosophical transactions of the Royal Society of London Series B, Biological sciences 2017;372(1732):20160276–10. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. DeCaprio JA, Garcea RL. A cornucopia of human polyomaviruses. Nat Rev Microbiol 2013;11(4):264–76. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Delbue S, Elia F, Signorini L, Bella R, Villani S, Marchioni E, et al. Human polyomavirus 6 DNA in the cerebrospinal fluid of an HIV-positive patient with leukoencephalopathy. Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology 2015;68:24–7. [DOI] [PubMed] [Google Scholar]
  28. Erickson KD, Garcea RL, Tsai B. Ganglioside GT1b is a putative host cell receptor for the Merkel cell polyomavirus. J Virol 2009;83(19):10275–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Fava P, Merlino C, Novelli M, Ponti R, Galliano I, Montanari P, et al. HPyV6, HPyV7 and TSPyV DNA sequences detection in skin disease patients and healthy subjects. Journal of the European Academy of Dermatology and Venereology 2016;30(4):624–7. [DOI] [PubMed] [Google Scholar]
  30. Feng H, Shuda M, Chang Y, Moore PS. Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science 2008;319(5866):1096–100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Fischer MK, Kao GF, Nguyen HP, Drachenberg CB, Rady PL, Tyring SK, et al. Specific detection of trichodysplasia spinulosa–associated polyomavirus DNA in skin and renal allograft tissues in a patient with trichodysplasia spinulosa. Archives of Dermatology 2012;148(6):726–33. [DOI] [PubMed] [Google Scholar]
  32. Franzen J, Ramqvist T, Bogdanovic G, Grun N, Mattson J, Dalianis T. Studies of human polyomaviruses, with HPyV7, BKPyV, and JCPyV present in urine of allogeneic hematopoietic stem cell transplanted patients with or without hemorrhagic cystitis. Transpl Infect Dis 2016;18(2):240–6. [DOI] [PubMed] [Google Scholar]
  33. Frouin E, Guillot B, Larrieux M, Tempier A, Boulle N, Foulongne V, et al. Cutaneous epithelial tumors induced by vemurafenib involve the MAPK and Pi3KCA pathways but not HPV nor HPyV viral infection. PLoS ONE 2014;9(10):e110478–6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Fukumoto H, Li T-C, Kataoka M, Hasegawa H, Wakita T, Saeki H, et al. Seroprevalence of trichodysplasia spinulosa-associated polyomavirus in Japan. Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology 2015;65:76–82. [DOI] [PubMed] [Google Scholar]
  35. Gardner SD, Field AM, Coleman DV, Hulme B. New human papovavirus (B.K.) isolated from urine after renal transplantation. Lancet 1971;1(7712):1253–7. [DOI] [PubMed] [Google Scholar]
  36. Gaynor AM, Nissen MD, Whiley DM, Mackay IM, Lambert SB, Wu G, et al. Identification of a novel polyomavirus from patients with acute respiratory tract infections. PLoS Pathog 2007;3(5):e64. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Gossai A, Waterboer T, Hoen AG, Farzan SF, Nelson HH, Michel A, et al. Human polyomaviruses and incidence of cutaneous squamous cell carcinoma in the New Hampshire skin cancer study. Cancer Medicine 2016a;5(6):1239–50. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Gossai A, Waterboer T, Nelson HH, Michel A, Willhauck-Fleckenstein M, Farzan SF, et al. Seroepidemiology of Human Polyomaviruses in a US Population. American Journal of Epidemiology 2016b;183(1):61–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Haeggblom L, Franzén J, Näsman A. Human polyomavirus DNA detection in keratoacanthoma and Spitz naevus: no evidence for a causal role. Journal of Clinical Pathology 2017;70(5):451–3. [DOI] [PubMed] [Google Scholar]
  40. Hampras SS, Giuliano AR, Lin HY, Fisher KJ, Abrahamsen ME, McKay-Chopin S, et al. Natural history of polyomaviruses in men: the HPV infection in men (HIM) study. J Infect Dis 2015;211(9):1437–46. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Hashida Y, Higuchi T, Matsuzaki S, Nakajima K, Sano S, Daibata M. Prevalence and Genetic Variability of Human Polyomaviruses 6 and 7 in Healthy Skin Among Asymptomatic Individuals. The Journal of infectious diseases 2017:1–11. [DOI] [PubMed] [Google Scholar]
  42. Haycox CL, Kim S, Fleckman P, Smith LT, Piepkorn M, Sundberg JP, et al. Trichodysplasia spinulosa--a newly described folliculocentric viral infection in an immunocompromised host. J Investig Dermatol Symp Proc 1999;4(3):268–71. [DOI] [PubMed] [Google Scholar]
  43. Heaphy MR Jr., Shamma HN, Hickmann M, White MJ. Cyclosporine-induced folliculodystrophy. J Am Acad Dermatol 2004;50(2):310–5. [DOI] [PubMed] [Google Scholar]
  44. Ho J, Jedrych JJ, Feng H, Natalie AA, Grandinetti L, Mirvish E, et al. Human Polyomavirus 7-Associated Pruritic Rash and Viremia in Transplant Recipients. J Infect Dis 2014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Kamminga S, van der Meijden E, Wunderink HF, Touze A, Zaaijer HL, Feltkamp MCW. Development and Evaluation of a Broad Bead-Based Multiplex Immunoassay To Measure IgG Seroreactivity against Human Polyomaviruses. J Clin Microbiol 2018;56(4). [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Kassar R, Chang J, Chan A-W, Lilly LB, Al Habeeb A, Rotstein C. Leflunomide for the treatment of trichodysplasia spinulosa in a liver transplant recipient. Transplant Infectious Disease 2017;19(4):e12702–4. [DOI] [PubMed] [Google Scholar]
  47. Kassem A, Schopflin A, Diaz C, Weyers W, Stickeler E, Werner M, et al. Frequent detection of Merkel cell polyomavirus in human Merkel cell carcinomas and identification of a unique deletion in the VP1 gene. Cancer Res 2008;68(13):5009–13. [DOI] [PubMed] [Google Scholar]
  48. Kazem S, van der Meijden E, Kooijman S, Rosenberg AS, Hughey LC, Browning JC, et al. Trichodysplasia spinulosa is characterized by active polyomavirus infection. J Clin Virol 2012;53(3):225–30. [DOI] [PubMed] [Google Scholar]
  49. Kazem S, van der Meijden E, Wang RC, Rosenberg AS, Pope E, Benoit T, et al. Polyomavirus-associated Trichodysplasia spinulosa involves hyperproliferation, pRB phosphorylation and upregulation of p16 and p21. PLoS One 2014;9(10):e108947. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Kwun HJ, Shuda M, Feng H, Camacho CJ, Moore PS, Chang Y. Merkel cell polyomavirus small T antigen controls viral replication and oncoprotein expression by targeting the cellular ubiquitin ligase SCFFbw7. Cell Host Microbe 2013;14(2):125–35. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Leitenberger JJ, Abdelmalek M, Wang RC, Strasfeld L, Hopkins RS. Two cases of trichodysplasia spinulosa responsive to compounded topical cidofovir 3% cream. JAAD Case Reports 2015;1(6):S33–5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Martel-Jantin C, Pedergnana V, Nicol JT, Leblond V, Tregouet DA, Tortevoye P, et al. Merkel cell polyomavirus infection occurs during early childhood and is transmitted between siblings. J Clin Virol 2013;58(1):288–91. [DOI] [PubMed] [Google Scholar]
  53. Matthews MR, Wang RC, Reddick RL, Saldivar VA, Browning JC. Viral-associated trichodysplasia spinulosa: a case with electron microscopic and molecular detection of the trichodysplasia spinulosa-associated human polyomavirus. J Cutan Pathol 2011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Mazzoni E, Rotondo JC, Marracino L, Selvatici R, Bononi I, Torreggiani E, et al. Detection of Merkel Cell Polyomavirus DNA in Serum Samples of Healthy Blood Donors. Frontiers in Oncology 2017;7:1096–7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Moshiri AS, Doumani R, Yelistratova L, Blom A, Lachance K, Shinohara MM, et al. Polyomavirus-Negative Merkel Cell Carcinoma: A More Aggressive Subtype Based on Analysis of 282 Cases Using Multimodal Tumor Virus Detection. J Invest Dermatol 2017;137(4):819–27. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Nguyen KD, Lee EE, Yue Y, Štork J, Pock L, North JP, et al. Human polyomavirus 6 and 7 are associated with pruritic and dyskeratotic dermatoses. Journal of the American Academy of Dermatology 2017;76(5):932–40.e3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Nicol JT, Leblond V, Arnold F, Guerra G, Mazzoni E, Tognon M, et al. Seroprevalence of human Malawi polyomavirus. J Clin Microbiol 2014;52(1):321–3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Nicol JT, Robinot R, Carpentier A, Carandina G, Mazzoni E, Tognon M, et al. Age-specific seroprevalences of merkel cell polyomavirus, human polyomaviruses 6, 7, and 9, and trichodysplasia spinulosa-associated polyomavirus. Clin Vaccine Immunol 2013;20(3):363–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Padgett BL, Walker DL, ZuRhein GM, Eckroade RJ, Dessel BH. Cultivation of papova-like virus from human brain with progressive multifocal leucoencephalopathy. Lancet 1971;1(7712):1257–60. [DOI] [PubMed] [Google Scholar]
  60. Pantulu ND, Pallasch CP, Kurz AK, Kassem A, Frenzel L, Sodenkamp S, et al. Detection of a novel truncating Merkel cell polyomavirus large T antigen deletion in chronic lymphocytic leukemia cells. Blood 2010;116(24):5280–4. [DOI] [PubMed] [Google Scholar]
  61. Pedergnana V, Martel-Jantin C, Nicol JTJ, Leblond V, Tortevoye P, Coursaget P, et al. Trichodysplasia Spinulosa Polyomavirus Infection Occurs during Early Childhood with Intrafamilial Transmission, Especially from Mother to Child. The Journal of investigative dermatology 2017;137(5):1181–3. [DOI] [PubMed] [Google Scholar]
  62. Pock L, Stork J. Two case reports of columnar dyskeratosis, an unusual keratinisation disorder. Dermatology 2010;220(3):274–9. [DOI] [PubMed] [Google Scholar]
  63. Rascovan N, Bouchard SM, Grob JJ, Collet-Villette AM, Gaudy-Marqueste C, Penicaud M, et al. Human polyomavirus-6 infecting lymph nodes of a patient with an angiolymphoid hyperplasia with eosinophilia or Kimura disease. Clin Infect Dis 2016. [DOI] [PubMed] [Google Scholar]
  64. Rennspiess D, Pujari S, Keijzers M, Abdul-Hamid MA, Hochstenbag M, Dingemans A-M, et al. Detection of human polyomavirus 7 in human thymic epithelial tumors. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 2015;10(2):360–6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Rockett RJ, Sloots TP, Bowes S, O’Neill N, Ye S, Robson J, et al. Detection of novel polyomaviruses, TSPyV, HPyV6, HPyV7, HPyV9 and MWPyV in feces, urine, blood, respiratory swabs and cerebrospinal fluid. PLoS One 2013;8(5):e62764. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Rouanet J, Aubin F, Gaboriaud P, Berthon P, Feltkamp MC, Bessenay L, et al. Trichodysplasia spinulosa: a polyomavirus infection specifically targeting follicular keratinocytes in immunocompromised patients. The British journal of dermatology 2016;174(3):629–32. [DOI] [PubMed] [Google Scholar]
  67. Rozenblatt-Rosen O, Deo RC, Padi M, Adelmant G, Calderwood MA, Rolland T, et al. Interpreting cancer genomes using systematic host network perturbations by tumour virus proteins. Nature 2012;487(7408):491–5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Salakova M, Koslabova E, Vojtechova Z, Tachezy R, Sroller V. Detection of human polyomaviruses MCPyV, HPyV6, and HPyV7 in malignant and non-malignant tonsillar tissues. J Med Virol 2016;88(4):695–702. [DOI] [PubMed] [Google Scholar]
  69. Santesteban R, Feito M, Mayor A, Beato M, Ramos E, de Lucas R. Trichodysplasia Spinulosa in a 20-Month-Old Girl With a Good Response to Topical Cidofovir 1%. PEDIATRICS 2015;136(6):e1646–9. [DOI] [PubMed] [Google Scholar]
  70. Scheidtmann KH, Mumby MC, Rundell K, Walter G. Dephosphorylation of simian virus 40 large-T antigen and p53 protein by protein phosphatase 2A: inhibition by small-t antigen. Mol Cell Biol 1991;11(4):1996–2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. Schowalter RM, Pastrana DV, Pumphrey KA, Moyer AL, Buck CB. Merkel cell polyomavirus and two previously unknown polyomaviruses are chronically shed from human skin. Cell Host Microbe 2010;7(6):509–15. [DOI] [PMC free article] [PubMed] [Google Scholar]
  72. Schowalter RM, Reinhold WC, Buck CB. Entry tropism of BK and Merkel cell polyomaviruses in cell culture. PLoS One 2012;7(7):e42181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  73. Schrama D, Buck CB, Houben R, Becker JC. No evidence for association of HPyV6 or HPyV7 with different skin cancers. J Invest Dermatol 2012;132(1):239–41. [DOI] [PubMed] [Google Scholar]
  74. Schrama D, Groesser L, Ugurel S, Hafner C, Pastrana DV, Buck CB, et al. Presence of human polyomavirus 6 in mutation-specific BRAF inhibitor-induced epithelial proliferations. JAMA Dermatol 2014;150(11):1180–6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  75. Schuchner S, Wintersberger E. Binding of polyomavirus small T antigen to protein phosphatase 2A is required for elimination of p27 and support of S-phase induction in concert with large T antigen. J Virol 1999;73(11):9266–73. [DOI] [PMC free article] [PubMed] [Google Scholar]
  76. Scola N, Wieland U, Silling S, Altmeyer P, Stucker M, Kreuter A. Prevalence of human polyomaviruses in common and rare types of non-Merkel cell carcinoma skin cancer. Br J Dermatol 2012;167(6):1315–20. [DOI] [PubMed] [Google Scholar]
  77. Seo GJ, Chen CJ, Sullivan CS. Merkel cell polyomavirus encodes a microRNA with the ability to autoregulate viral gene expression. Virology 2009;383(2):183–7. [DOI] [PubMed] [Google Scholar]
  78. Shuda M, Kwun HJ, Feng H, Chang Y, Moore PS. Human Merkel cell polyomavirus small T antigen is an oncoprotein targeting the 4E-BP1 translation regulator. J Clin Invest 2011;121(9):3623–34. [DOI] [PMC free article] [PubMed] [Google Scholar]
  79. Siebrasse EA, Reyes A, Lim ES, Zhao G, Mkakosya RS, Manary MJ, et al. Identification of MW polyomavirus, a novel polyomavirus in human stool. Journal of Virology 2012;86(19):10321–6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  80. Smith SDB, Erdag G, Cuda JD, Rangwala S, Girardi N, Bibee K, et al. Treatment of human polyomavirus-7-associated rash and pruritus with topical cidofovir in a lung transplant patient: Case report and literature review. Transpl Infect Dis 2018;20(1). [DOI] [PubMed] [Google Scholar]
  81. Sperling LC, Tomaszewski M-M, Thomas DA. Viral-associated trichodysplasia in patients who are immunocompromised. Journal of American Dermatology 2004;50(2):318–22. [DOI] [PubMed] [Google Scholar]
  82. Sroller V, Hamsikova E, Ludvikova V, Musil J, Nemeckova S, Salakova M. Seroprevalence rates of HPyV6, HPyV7, TSPyV, HPyV9, MWPyV and KIPyV polyomaviruses among the healthy blood donors. J Med Virol 2016;88(7):1254–61. [DOI] [PubMed] [Google Scholar]
  83. Stehle T, Yan Y, Benjamin TL, Harrison SC. Structure of murine polyomavirus complexed with an oligosaccharide receptor fragment. Nature 1994;369(6476):160–3. [DOI] [PubMed] [Google Scholar]
  84. Stroh LJ, Neu U, Blaum BS, Buch MH, Garcea RL, Stehle T. Structure analysis of the major capsid proteins of human polyomaviruses 6 and 7 reveals an obstructed sialic acid binding site. J Virol 2014;88(18):10831–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  85. Sullivan CS, Cantalupo P, Pipas JM. The molecular chaperone activity of simian virus 40 large T antigen is required to disrupt Rb-E2F family complexes by an ATP-dependent mechanism. Mol Cell Biol 2000;20(17):6233–43. [DOI] [PMC free article] [PubMed] [Google Scholar]
  86. Toptan T, Yousem SA, Ho J, Matsushima Y, Stabile LP, Fernández-Figueras M-T, et al. Survey for human polyomaviruses in cancer. JCI Insight 2016;1(2):1–14. [DOI] [PMC free article] [PubMed] [Google Scholar]
  87. Tsuzuki S, Fukumoto H, Mine S, Sato N, Mochizuki M, Hasegawa H, et al. Detection of trichodysplasia spinulosa-associated polyomavirus in a fatal case of myocarditis in a seven-month-old girl. International journal of clinical and experimental pathology 2014;7(8):5308–12. [PMC free article] [PubMed] [Google Scholar]
  88. Urbano PR, Nali LH, Bicalho CS, Pierrotti LC, David-Neto E, Pannuti CS, et al. New findings about trichodysplasia spinulosa-associated polyomavirus (TSPyV)--novel qPCR detects TSPyV-DNA in blood samples. Diagn Microbiol Infect Dis 2016;84(2):123–4. [DOI] [PubMed] [Google Scholar]
  89. van der Meijden E, Bialasiewicz S, Rockett RJ, Tozer SJ, Sloots TP, Feltkamp MCW. Different serologic behavior of MCPyV, TSPyV, HPyV6, HPyV7 and HPyV9 polyomaviruses found on the skin. PLoS ONE 2013;8(11):e81078–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  90. van der Meijden E, Feltkamp M. The Human Polyomavirus Middle and Alternative T-Antigens; Thoughts on Roles and Relevance to Cancer. Front Microbiol 2018;9:398. [DOI] [PMC free article] [PubMed] [Google Scholar]
  91. van der Meijden E, Horváth B, Nijland M, de Vries K, Rácz EK, Diercks GF, et al. Primary Polyomavirus Infection, Not Reactivation, as the Cause of Trichodysplasia Spinulosa in Immunocompromised Patients. The Journal of infectious diseases 2017;215(7):1080–4. [DOI] [PubMed] [Google Scholar]
  92. van der Meijden E, Janssens RW, Lauber C, Bouwes Bavinck JN, Gorbalenya AE, Feltkamp MC. Discovery of a new human polyomavirus associated with trichodysplasia spinulosa in an immunocompromized patient. PLoS Pathog 2010;6(7):e1001024. [DOI] [PMC free article] [PubMed] [Google Scholar]
  93. van der Meijden E, Kazem S, Burgers MM, Janssens R, Bouwes Bavinck JN, de Melker H, et al. Seroprevalence of trichodysplasia spinulosa-associated polyomavirus. Emerg Infect Dis 2011;17(8):1355–63. [DOI] [PMC free article] [PubMed] [Google Scholar]
  94. van der Meijden E, Kazem S, Dargel CA, van Vuren N, Hensbergen PJ, Feltkamp MC. Characterization of T Antigens, Including Middle T and Alternative T, Expressed by the Human Polyomavirus Associated with Trichodysplasia Spinulosa. J Virol 2015;89(18):9427–39. [DOI] [PMC free article] [PubMed] [Google Scholar]
  95. Van Ghelue M, Khan MT, Ehlers B, Moens U. Genome analysis of the new human polyomaviruses. Rev Med Virol 2012;22(6):354–77. [DOI] [PubMed] [Google Scholar]
  96. Wanat KA, Holler PD, Dentchev T, Simbiri K, Robertson E, Seykora JT, et al. Viral-associated trichodysplasia: characterization of a novel polyomavirus infection with therapeutic insights. Archives of Dermatology 2012;148(2):219–23. [DOI] [PMC free article] [PubMed] [Google Scholar]
  97. Wieland U, Silling S, Hellmich M, Potthoff A, Pfister H, Kreuter A. Human polyomaviruses 6, 7, 9, 10 and Trichodysplasia spinulosa-associated polyomavirus in HIV-infected men. J Gen Virol 2014;95(Pt 4):928–32. [DOI] [PubMed] [Google Scholar]
  98. Yu G, Greninger AL, Isa P, Phan TG, Martinez MA, de la Luz Sanchez M, et al. Discovery of a novel polyomavirus in acute diarrheal samples from children. PLoS One 2012;7(11):e49449. [DOI] [PMC free article] [PubMed] [Google Scholar]
  99. Zheng W-z, Wei T-l, Ma F-l, Yuan W-m, Zhang Q, Zhang Y-x, et al. Human polyomavirus type six in respiratory samples from hospitalized children with respiratory tract infections in Beijing, China. Virology Journal 2015;12(1):166–6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  100. Zhou B, Arnett DR, Yu X, Brewster A, Sowd GA, Xie CL, et al. Structural basis for the interaction of a hexameric replicative helicase with the regulatory subunit of human DNA polymerase alpha-primase. J Biol Chem 2012;287(32):26854–66. [DOI] [PMC free article] [PubMed] [Google Scholar]

RESOURCES