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Importance of Promyelocytic Leukema Protein (PML) for Kaposi’s Sarcoma-Associated Herpesvirus Lytic Replication

Many DNA virus replication-related proteins are associated with promyelocytic leukemia protein (PML), a component of nuclear domain 10 (ND10), which has been investigated for its potential involvement in viral replication. In the case of Kaposi’s sarcoma-associated herpesvirus (KSHV) lytic gene prod...

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Autores principales: Hossain, Md. Golzar, Ohsaki, Eriko, Honda, Tomoyuki, Ueda, Keiji
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6186782/
https://www.ncbi.nlm.nih.gov/pubmed/30349510
http://dx.doi.org/10.3389/fmicb.2018.02324
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author Hossain, Md. Golzar
Ohsaki, Eriko
Honda, Tomoyuki
Ueda, Keiji
author_facet Hossain, Md. Golzar
Ohsaki, Eriko
Honda, Tomoyuki
Ueda, Keiji
author_sort Hossain, Md. Golzar
collection PubMed
description Many DNA virus replication-related proteins are associated with promyelocytic leukemia protein (PML), a component of nuclear domain 10 (ND10), which has been investigated for its potential involvement in viral replication. In the case of Kaposi’s sarcoma-associated herpesvirus (KSHV) lytic gene products, K8 (K-bZIP), ORF59, and ORF75 have been shown to colocalize with PML, but its importance in KSHV lytic replication is still unclear. In this study, we analyzed the functional influence of PML on KSHV latency and lytic replication in KSHV-infected primary effusion lymphoma (PEL) cell lines. Stable PML-knockout (BC3-PML(KO)) and PML-overexpressing BC3 cells (BC3(PML)) were successfully generated and the latency and reactivation status were analyzed. The results demonstrated that neither KSHV latency nor the episome copy number was affected in BC3-PML(KO) cells. In the reactivation phase, the expression dynamics of KSHV immediate-early or early lytic proteins such as RTA, K9 (vIRF1), K5, K3, ORF59, and K8 (K-bZIP) were comparable between wild-type, control BC3, and BC3-PML(KO) cells. Interestingly, KSHV lytic replication, virion production, and expression of late genes were downregulated in BC3-PML(KO) cells and upregulated in BC3(PML) cells, compared to those in control or wild-type BC3 cells. Moreover, exogenous PML increased the size of the PML dots and recruited additional K8 (K-bZIP) to PML-NBs as dots. Therefore, PML would function as a positive regulator for KSHV lytic DNA replication by recruiting KSHV replication factors such as 8 (K-bZIP) or ORF59 to the PML-NBs.
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spelling pubmed-61867822018-10-22 Importance of Promyelocytic Leukema Protein (PML) for Kaposi’s Sarcoma-Associated Herpesvirus Lytic Replication Hossain, Md. Golzar Ohsaki, Eriko Honda, Tomoyuki Ueda, Keiji Front Microbiol Microbiology Many DNA virus replication-related proteins are associated with promyelocytic leukemia protein (PML), a component of nuclear domain 10 (ND10), which has been investigated for its potential involvement in viral replication. In the case of Kaposi’s sarcoma-associated herpesvirus (KSHV) lytic gene products, K8 (K-bZIP), ORF59, and ORF75 have been shown to colocalize with PML, but its importance in KSHV lytic replication is still unclear. In this study, we analyzed the functional influence of PML on KSHV latency and lytic replication in KSHV-infected primary effusion lymphoma (PEL) cell lines. Stable PML-knockout (BC3-PML(KO)) and PML-overexpressing BC3 cells (BC3(PML)) were successfully generated and the latency and reactivation status were analyzed. The results demonstrated that neither KSHV latency nor the episome copy number was affected in BC3-PML(KO) cells. In the reactivation phase, the expression dynamics of KSHV immediate-early or early lytic proteins such as RTA, K9 (vIRF1), K5, K3, ORF59, and K8 (K-bZIP) were comparable between wild-type, control BC3, and BC3-PML(KO) cells. Interestingly, KSHV lytic replication, virion production, and expression of late genes were downregulated in BC3-PML(KO) cells and upregulated in BC3(PML) cells, compared to those in control or wild-type BC3 cells. Moreover, exogenous PML increased the size of the PML dots and recruited additional K8 (K-bZIP) to PML-NBs as dots. Therefore, PML would function as a positive regulator for KSHV lytic DNA replication by recruiting KSHV replication factors such as 8 (K-bZIP) or ORF59 to the PML-NBs. Frontiers Media S.A. 2018-10-08 /pmc/articles/PMC6186782/ /pubmed/30349510 http://dx.doi.org/10.3389/fmicb.2018.02324 Text en Copyright © 2018 Hossain, Ohsaki, Honda and Ueda. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Hossain, Md. Golzar
Ohsaki, Eriko
Honda, Tomoyuki
Ueda, Keiji
Importance of Promyelocytic Leukema Protein (PML) for Kaposi’s Sarcoma-Associated Herpesvirus Lytic Replication
title Importance of Promyelocytic Leukema Protein (PML) for Kaposi’s Sarcoma-Associated Herpesvirus Lytic Replication
title_full Importance of Promyelocytic Leukema Protein (PML) for Kaposi’s Sarcoma-Associated Herpesvirus Lytic Replication
title_fullStr Importance of Promyelocytic Leukema Protein (PML) for Kaposi’s Sarcoma-Associated Herpesvirus Lytic Replication
title_full_unstemmed Importance of Promyelocytic Leukema Protein (PML) for Kaposi’s Sarcoma-Associated Herpesvirus Lytic Replication
title_short Importance of Promyelocytic Leukema Protein (PML) for Kaposi’s Sarcoma-Associated Herpesvirus Lytic Replication
title_sort importance of promyelocytic leukema protein (pml) for kaposi’s sarcoma-associated herpesvirus lytic replication
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6186782/
https://www.ncbi.nlm.nih.gov/pubmed/30349510
http://dx.doi.org/10.3389/fmicb.2018.02324
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