Human polyomavirus 7 (HPyV7)-associated dermatoses : novel molecular mechanism driven by viral activation of 4E-BP1 and MEK-ERK-cJun
© 2018 The International Society of Dermatology..
A number of pruritic skin conditions arising in immunocompromised patients are associated with viral infection. Recently, human polyomavirus 7 (HPyV7) has been implicated in the pathogenesis of eruptive pruritic parakeratotic and dyskeratotic dermatoses with distinct "peacock plumage" histology. While expression of HPyV7 viral protein, namely small tumor (sT) antigen, is prominent within lesional tissue, the functional role of HPyV7 in cutaneous pathobiology is not yet known. In this study, we demonstrate a novel role for HPyV7 sT antigen in pathways important for the maintenance of keratinocyte structure and function. In particular, HPyV7 sT was found to dysregulate protein phosphatase 2A through physical interactions that led to activation of MEK/ERK/c-Jun and 4E-BP1 (proteins that contribute to disorganized keratinocyte growth as well as hyperproliferative and inflammatory states). Given that HPyV7 actively infects keratinocytes and sT antigen is highly expressed in pruritic dyskeratotic/parakeratotic dermatoses, our data provide important mechanistic evidence supporting a pathogenic role for HPyV7 in cutaneous disease.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:58 |
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| Enthalten in: |
International journal of dermatology - 58(2019), 4 vom: 28. Apr., Seite 383-387 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wu, Julie H [VerfasserIn] |
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| Links: |
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| Themen: |
Adaptor Proteins, Signal Transducing |
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| Anmerkungen: |
Date Completed 28.06.2019 Date Revised 09.12.2020 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1111/ijd.14315 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM291672248 |
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| 100 | 1 | |a Wu, Julie H |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Human polyomavirus 7 (HPyV7)-associated dermatoses |b novel molecular mechanism driven by viral activation of 4E-BP1 and MEK-ERK-cJun |
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| 500 | |a Date Completed 28.06.2019 | ||
| 500 | |a Date Revised 09.12.2020 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2018 The International Society of Dermatology. | ||
| 520 | |a A number of pruritic skin conditions arising in immunocompromised patients are associated with viral infection. Recently, human polyomavirus 7 (HPyV7) has been implicated in the pathogenesis of eruptive pruritic parakeratotic and dyskeratotic dermatoses with distinct "peacock plumage" histology. While expression of HPyV7 viral protein, namely small tumor (sT) antigen, is prominent within lesional tissue, the functional role of HPyV7 in cutaneous pathobiology is not yet known. In this study, we demonstrate a novel role for HPyV7 sT antigen in pathways important for the maintenance of keratinocyte structure and function. In particular, HPyV7 sT was found to dysregulate protein phosphatase 2A through physical interactions that led to activation of MEK/ERK/c-Jun and 4E-BP1 (proteins that contribute to disorganized keratinocyte growth as well as hyperproliferative and inflammatory states). Given that HPyV7 actively infects keratinocytes and sT antigen is highly expressed in pruritic dyskeratotic/parakeratotic dermatoses, our data provide important mechanistic evidence supporting a pathogenic role for HPyV7 in cutaneous disease | ||
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| 700 | 1 | |a Narayanan, Deepika |e verfasserin |4 aut | |
| 700 | 1 | |a Simonette, Rebecca A |e verfasserin |4 aut | |
| 700 | 1 | |a Rady, Peter L |e verfasserin |4 aut | |
| 700 | 1 | |a Tyring, Stephen K |e verfasserin |4 aut | |
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