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The RBP-Jκ Binding Sites within the RTA Promoter Regulate KSHV Latent Infection and Cell Proliferation
Kaposi's sarcoma-associated herpesvirus (KSHV) is tightly linked to at least two lymphoproliferative disorders, primary effusion lymphoma (PEL) and multicentric Castleman's disease (MCD). However, the development of KSHV-mediated lymphoproliferative disease is not fully understood. Here, w...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3257303/ https://www.ncbi.nlm.nih.gov/pubmed/22253595 http://dx.doi.org/10.1371/journal.ppat.1002479 |
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author | Lu, Jie Verma, Subhash C. Cai, Qiliang Saha, Abhik Dzeng, Richard Kuo Robertson, Erle S. |
author_facet | Lu, Jie Verma, Subhash C. Cai, Qiliang Saha, Abhik Dzeng, Richard Kuo Robertson, Erle S. |
author_sort | Lu, Jie |
collection | PubMed |
description | Kaposi's sarcoma-associated herpesvirus (KSHV) is tightly linked to at least two lymphoproliferative disorders, primary effusion lymphoma (PEL) and multicentric Castleman's disease (MCD). However, the development of KSHV-mediated lymphoproliferative disease is not fully understood. Here, we generated two recombinant KSHV viruses deleted for the first RBP-Jκ binding site (RTA(1st)) and all three RBP-Jκ binding sites (RTA(all)) within the RTA promoter. Our results showed that RTA(1st) and RTA(all) recombinant viruses possess increased viral latency and a decreased capability for lytic replication in HEK 293 cells, enhancing colony formation and proliferation of infected cells. Furthermore, recombinant RTA(1st) and RTA(all) viruses showed greater infectivity in human peripheral blood mononuclear cells (PBMCs) relative to wt KSHV. Interestingly, KSHV BAC36 wt, RTA(1st) and RTA(all) recombinant viruses infected both T and B cells and all three viruses efficiently infected T and B cells in a time-dependent manner early after infection. Also, the capability of both RTA(1st) and RTA(all) recombinant viruses to infect CD19+ B cells was significantly enhanced. Surprisingly, RTA(1st) and RTA(all) recombinant viruses showed greater infectivity for CD3+ T cells up to 7 days. Furthermore, studies in Telomerase-immortalized human umbilical vein endothelial (TIVE) cells infected with KSHV corroborated our data that RTA(1st) and RTA(all) recombinant viruses have enhanced ability to persist in latently infected cells with increased proliferation. These recombinant viruses now provide a model to explore early stages of primary infection in human PBMCs and development of KSHV-associated lymphoproliferative diseases. |
format | Online Article Text |
id | pubmed-3257303 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-32573032012-01-17 The RBP-Jκ Binding Sites within the RTA Promoter Regulate KSHV Latent Infection and Cell Proliferation Lu, Jie Verma, Subhash C. Cai, Qiliang Saha, Abhik Dzeng, Richard Kuo Robertson, Erle S. PLoS Pathog Research Article Kaposi's sarcoma-associated herpesvirus (KSHV) is tightly linked to at least two lymphoproliferative disorders, primary effusion lymphoma (PEL) and multicentric Castleman's disease (MCD). However, the development of KSHV-mediated lymphoproliferative disease is not fully understood. Here, we generated two recombinant KSHV viruses deleted for the first RBP-Jκ binding site (RTA(1st)) and all three RBP-Jκ binding sites (RTA(all)) within the RTA promoter. Our results showed that RTA(1st) and RTA(all) recombinant viruses possess increased viral latency and a decreased capability for lytic replication in HEK 293 cells, enhancing colony formation and proliferation of infected cells. Furthermore, recombinant RTA(1st) and RTA(all) viruses showed greater infectivity in human peripheral blood mononuclear cells (PBMCs) relative to wt KSHV. Interestingly, KSHV BAC36 wt, RTA(1st) and RTA(all) recombinant viruses infected both T and B cells and all three viruses efficiently infected T and B cells in a time-dependent manner early after infection. Also, the capability of both RTA(1st) and RTA(all) recombinant viruses to infect CD19+ B cells was significantly enhanced. Surprisingly, RTA(1st) and RTA(all) recombinant viruses showed greater infectivity for CD3+ T cells up to 7 days. Furthermore, studies in Telomerase-immortalized human umbilical vein endothelial (TIVE) cells infected with KSHV corroborated our data that RTA(1st) and RTA(all) recombinant viruses have enhanced ability to persist in latently infected cells with increased proliferation. These recombinant viruses now provide a model to explore early stages of primary infection in human PBMCs and development of KSHV-associated lymphoproliferative diseases. Public Library of Science 2012-01-12 /pmc/articles/PMC3257303/ /pubmed/22253595 http://dx.doi.org/10.1371/journal.ppat.1002479 Text en Lu et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Lu, Jie Verma, Subhash C. Cai, Qiliang Saha, Abhik Dzeng, Richard Kuo Robertson, Erle S. The RBP-Jκ Binding Sites within the RTA Promoter Regulate KSHV Latent Infection and Cell Proliferation |
title | The RBP-Jκ Binding Sites within the RTA Promoter Regulate KSHV Latent Infection and Cell Proliferation |
title_full | The RBP-Jκ Binding Sites within the RTA Promoter Regulate KSHV Latent Infection and Cell Proliferation |
title_fullStr | The RBP-Jκ Binding Sites within the RTA Promoter Regulate KSHV Latent Infection and Cell Proliferation |
title_full_unstemmed | The RBP-Jκ Binding Sites within the RTA Promoter Regulate KSHV Latent Infection and Cell Proliferation |
title_short | The RBP-Jκ Binding Sites within the RTA Promoter Regulate KSHV Latent Infection and Cell Proliferation |
title_sort | rbp-jκ binding sites within the rta promoter regulate kshv latent infection and cell proliferation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3257303/ https://www.ncbi.nlm.nih.gov/pubmed/22253595 http://dx.doi.org/10.1371/journal.ppat.1002479 |
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