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Narayanan D, Tahseen D, Bartley BR, et al. Trichodysplasia spinulosa polyomavirus small T antigen synergistically modulates S6 protein translation and DNA damage response pathways to shape host cell environment. Virus Genes. 2022;doi: 10.1007/s11262-021-01880-7.
Narayanan, D., Tahseen, D., Bartley, B. R., Moore, S. A., Simonette, R., Rady, P. L., & Tyring, S. K. (2022). Trichodysplasia spinulosa polyomavirus small T antigen synergistically modulates S6 protein translation and DNA damage response pathways to shape host cell environment. Virus genes, . https://doi.org/10.1007/s11262-021-01880-7
Narayanan, Deepika, et al. "Trichodysplasia spinulosa polyomavirus small T antigen synergistically modulates S6 protein translation and DNA damage response pathways to shape host cell environment." Virus genes vol. (2022). doi: https://doi.org/10.1007/s11262-021-01880-7
Narayanan D, Tahseen D, Bartley BR, Moore SA, Simonette R, Rady PL, Tyring SK. Trichodysplasia spinulosa polyomavirus small T antigen synergistically modulates S6 protein translation and DNA damage response pathways to shape host cell environment. Virus Genes. 2022 Jan 09; doi: 10.1007/s11262-021-01880-7. Epub 2022 Jan 09. PMID: 35000075.
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Virus Genes. 2022 Jan 09; doi: 10.1007/s11262-021-01880-7. Epub 2022 Jan 09.

Trichodysplasia spinulosa polyomavirus small T antigen synergistically modulates S6 protein translation and DNA damage response pathways to shape host cell environment.

Virus genes

Deepika Narayanan, Danyal Tahseen, Brooke R Bartley, Stephen A Moore, Rebecca Simonette, Peter L Rady, Stephen K Tyring

Affiliations

  1. Department of Dermatology, McGovern Medical School at UT Health Science Center, 6431 Fannin Street, Houston, TX, 77030, USA.
  2. Rice University, Houston, TX, USA.
  3. Department of Dermatology, McGovern Medical School at UT Health Science Center, 6431 Fannin Street, Houston, TX, 77030, USA. [email protected].

PMID: 35000075 DOI: 10.1007/s11262-021-01880-7

Abstract

TSPyV is a viral agent linked to Trichodysplasia spinulosa, a disfiguring human skin disease which presents with hyperkeratotic spicule eruption in immunocompromised hosts. This proliferative disease state requires extensive modulation of the host cell environment. While the small T (sT) antigen of TSPyV has been postulated to cause widespread cellular perturbation, its specific substrates and their mechanistic connection are unclear. To identify the cellular substrates and pathways perturbed by TSPyV sT and propose a nuanced model that reconciles the multiple arms of TSPyV pathogenesis, changes in expression of several proteins and phospho-proteins in TSPyV sT expressing and TSPyV sT deletion mutant-expressing cell lysates were interrogated using Western blot assays. TSPyV sT expression exploits the DNA damage response pathway, by inducing hyperphosphorylation of ATM and 53BP1 and upregulation of BMI-1. Concurrently, sT dysregulates the S6 protein translation pathway via hyperphosphorylation of CDC2, p70 S6 kinase, S6, and PP1α. The S6

© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Keywords: DNA damage response; Molecular virology; Pathogenesis; Translational regulation; Trichodysplasia spinulosa (TS); Trichodysplasia spinulosa-associated polyomavirus (TSPyV); Virus-host interactions

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