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...

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Autores principales:	Jie Lu, Subhash C Verma, Qiliang Cai, Abhik Saha, Richard Kuo Dzeng, Erle S Robertson
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/c0e6797eb8564cd4a3494942dab28e22
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spelling	oai:doaj.org-article:c0e6797eb8564cd4a3494942dab28e222021-11-18T06:04:52ZThe RBP-Jκ binding sites within the RTA promoter regulate KSHV latent infection and cell proliferation.1553-73661553-737410.1371/journal.ppat.1002479https://doaj.org/article/c0e6797eb8564cd4a3494942dab28e222012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22253595/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Kaposi'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.Jie LuSubhash C VermaQiliang CaiAbhik SahaRichard Kuo DzengErle S RobertsonPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 8, Iss 1, p e1002479 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Jie Lu Subhash C Verma Qiliang Cai Abhik Saha Richard Kuo Dzeng Erle S Robertson The RBP-Jκ binding sites within the RTA promoter regulate KSHV latent infection and cell proliferation.
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	article
author	Jie Lu Subhash C Verma Qiliang Cai Abhik Saha Richard Kuo Dzeng Erle S Robertson
author_facet	Jie Lu Subhash C Verma Qiliang Cai Abhik Saha Richard Kuo Dzeng Erle S Robertson
author_sort	Jie Lu
title	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_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_sort	rbp-jκ binding sites within the rta promoter regulate kshv latent infection and cell proliferation.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/c0e6797eb8564cd4a3494942dab28e22
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The RBP-Jκ binding sites within the RTA promoter regulate KSHV latent infection and cell proliferation.

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