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Time-course of host cell transcription during the HTLV-1 transcriptional burst

The human T-cell leukemia virus type 1 (HTLV-1) transactivator protein Tax has pleiotropic functions in the host cell affecting cell-cycle regulation, DNA damage response pathways and apoptosis. These actions of Tax have been implicated in the persistence and pathogenesis of HTLV-1-infected cells. I...

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Autores principales: Kiik, Helen, Ramanayake, Saumya, Miura, Michi, Tanaka, Yuetsu, Melamed, Anat, Bangham, Charles R. M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9135347/
https://www.ncbi.nlm.nih.gov/pubmed/35576236
http://dx.doi.org/10.1371/journal.ppat.1010387
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author Kiik, Helen
Ramanayake, Saumya
Miura, Michi
Tanaka, Yuetsu
Melamed, Anat
Bangham, Charles R. M.
author_facet Kiik, Helen
Ramanayake, Saumya
Miura, Michi
Tanaka, Yuetsu
Melamed, Anat
Bangham, Charles R. M.
author_sort Kiik, Helen
collection PubMed
description The human T-cell leukemia virus type 1 (HTLV-1) transactivator protein Tax has pleiotropic functions in the host cell affecting cell-cycle regulation, DNA damage response pathways and apoptosis. These actions of Tax have been implicated in the persistence and pathogenesis of HTLV-1-infected cells. It is now known that tax expression occurs in transcriptional bursts of the proviral plus-strand, but the effects of the burst on host transcription are not fully understood. We carried out RNA sequencing of two naturally-infected T-cell clones transduced with a Tax-responsive Timer protein, which undergoes a time-dependent shift in fluorescence emission, to study transcriptional changes during successive phases of the HTLV-1 plus-strand burst. We found that the transcriptional regulation of genes involved in the NF-κB pathway, cell-cycle regulation, DNA damage response and apoptosis inhibition were immediate effects accompanying the plus-strand burst, and are limited to the duration of the burst. The results distinguish between the immediate and delayed effects of HTLV-1 reactivation on host transcription, and between clone-specific effects and those observed in both clones. The major transcriptional changes in the infected host T-cells observed here, including NF-κB, are transient, suggesting that these pathways are not persistently activated at high levels in HTLV-1-infected cells. The two clones diverged strongly in their expression of genes regulating the cell cycle. Up-regulation of senescence markers was a delayed effect of the proviral plus-strand burst and the up-regulation of some pro-apoptotic genes outlasted the burst. We found that activation of the aryl hydrocarbon receptor (AhR) pathway enhanced and prolonged the proviral burst, but did not increase the rate of reactivation. Our results also suggest that sustained plus-strand expression is detrimental to the survival of infected cells.
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spelling pubmed-91353472022-05-27 Time-course of host cell transcription during the HTLV-1 transcriptional burst Kiik, Helen Ramanayake, Saumya Miura, Michi Tanaka, Yuetsu Melamed, Anat Bangham, Charles R. M. PLoS Pathog Research Article The human T-cell leukemia virus type 1 (HTLV-1) transactivator protein Tax has pleiotropic functions in the host cell affecting cell-cycle regulation, DNA damage response pathways and apoptosis. These actions of Tax have been implicated in the persistence and pathogenesis of HTLV-1-infected cells. It is now known that tax expression occurs in transcriptional bursts of the proviral plus-strand, but the effects of the burst on host transcription are not fully understood. We carried out RNA sequencing of two naturally-infected T-cell clones transduced with a Tax-responsive Timer protein, which undergoes a time-dependent shift in fluorescence emission, to study transcriptional changes during successive phases of the HTLV-1 plus-strand burst. We found that the transcriptional regulation of genes involved in the NF-κB pathway, cell-cycle regulation, DNA damage response and apoptosis inhibition were immediate effects accompanying the plus-strand burst, and are limited to the duration of the burst. The results distinguish between the immediate and delayed effects of HTLV-1 reactivation on host transcription, and between clone-specific effects and those observed in both clones. The major transcriptional changes in the infected host T-cells observed here, including NF-κB, are transient, suggesting that these pathways are not persistently activated at high levels in HTLV-1-infected cells. The two clones diverged strongly in their expression of genes regulating the cell cycle. Up-regulation of senescence markers was a delayed effect of the proviral plus-strand burst and the up-regulation of some pro-apoptotic genes outlasted the burst. We found that activation of the aryl hydrocarbon receptor (AhR) pathway enhanced and prolonged the proviral burst, but did not increase the rate of reactivation. Our results also suggest that sustained plus-strand expression is detrimental to the survival of infected cells. Public Library of Science 2022-05-16 /pmc/articles/PMC9135347/ /pubmed/35576236 http://dx.doi.org/10.1371/journal.ppat.1010387 Text en © 2022 Kiik et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Kiik, Helen
Ramanayake, Saumya
Miura, Michi
Tanaka, Yuetsu
Melamed, Anat
Bangham, Charles R. M.
Time-course of host cell transcription during the HTLV-1 transcriptional burst
title Time-course of host cell transcription during the HTLV-1 transcriptional burst
title_full Time-course of host cell transcription during the HTLV-1 transcriptional burst
title_fullStr Time-course of host cell transcription during the HTLV-1 transcriptional burst
title_full_unstemmed Time-course of host cell transcription during the HTLV-1 transcriptional burst
title_short Time-course of host cell transcription during the HTLV-1 transcriptional burst
title_sort time-course of host cell transcription during the htlv-1 transcriptional burst
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9135347/
https://www.ncbi.nlm.nih.gov/pubmed/35576236
http://dx.doi.org/10.1371/journal.ppat.1010387
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