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

Siamaque Kazem, Els Van Der Meijden, Richard C. Wang, Arlene S. Rosenberg, Elena Pope, Taylor Benoit, Philip Fleckman, Mariet C.W. Feltkamp

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Article numbere108947
JournalPLoS ONE
Volume9
Issue number10
DOIs
Publication statusPublished - 7 Oct 2014

Cite this

Kazem, S., Van Der Meijden, E., Wang, R. C., Rosenberg, A. S., Pope, E., Benoit, T., ... Feltkamp, M. C. W. (2014). Polyomavirus-associated trichodysplasia spinulosa involves hyperproliferation, pRB phosphorylation and upregulation of p16 and p21. PLoS ONE, 9(10), [e108947]. https://doi.org/10.1371/journal.pone.0108947
Kazem, Siamaque ; Van Der Meijden, Els ; Wang, Richard C. ; Rosenberg, Arlene S. ; Pope, Elena ; Benoit, Taylor ; Fleckman, Philip ; Feltkamp, Mariet C.W. / Polyomavirus-associated trichodysplasia spinulosa involves hyperproliferation, pRB phosphorylation and upregulation of p16 and p21. In: PLoS ONE. 2014 ; Vol. 9, No. 10.
@article{26346816cd114b86adfb34aae435936d,
title = "Polyomavirus-associated trichodysplasia spinulosa involves hyperproliferation, pRB phosphorylation and upregulation of p16 and p21",
abstract = "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.",
author = "Siamaque Kazem and {Van Der Meijden}, Els and Wang, {Richard C.} and Rosenberg, {Arlene S.} and Elena Pope and Taylor Benoit and Philip Fleckman and Feltkamp, {Mariet C.W.}",
year = "2014",
month = "10",
day = "7",
doi = "10.1371/journal.pone.0108947",
language = "English",
volume = "9",
journal = "PLoS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "10",

}

Kazem, S, Van Der Meijden, E, Wang, RC, Rosenberg, AS, Pope, E, Benoit, T, Fleckman, P & Feltkamp, MCW 2014, 'Polyomavirus-associated trichodysplasia spinulosa involves hyperproliferation, pRB phosphorylation and upregulation of p16 and p21' PLoS ONE, vol. 9, no. 10, e108947. https://doi.org/10.1371/journal.pone.0108947

Polyomavirus-associated trichodysplasia spinulosa involves hyperproliferation, pRB phosphorylation and upregulation of p16 and p21. / Kazem, Siamaque; Van Der Meijden, Els; Wang, Richard C.; Rosenberg, Arlene S.; Pope, Elena; Benoit, Taylor; Fleckman, Philip; Feltkamp, Mariet C.W.

In: PLoS ONE, Vol. 9, No. 10, e108947, 07.10.2014.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Polyomavirus-associated trichodysplasia spinulosa involves hyperproliferation, pRB phosphorylation and upregulation of p16 and p21

AU - Kazem, Siamaque

AU - Van Der Meijden, Els

AU - Wang, Richard C.

AU - Rosenberg, Arlene S.

AU - Pope, Elena

AU - Benoit, Taylor

AU - Fleckman, Philip

AU - Feltkamp, Mariet C.W.

PY - 2014/10/7

Y1 - 2014/10/7

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84907806022&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0108947

DO - 10.1371/journal.pone.0108947

M3 - Article

VL - 9

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 10

M1 - e108947

ER -