KSHV miRNAs Decrease Expression of Lytic Genes in Latently Infected PEL and Endothelial Cells by Targeting Host Transcription Factors
Kaposi’s sarcoma-associated herpesvirus (KSHV) microRNAs are encoded in the latency-associated region. Knockdown of KSHV miR-K12-3 and miR-K12-11 increased expression of lytic genes in BC-3 cells, and increased virus production from latently infected BCBL-1 cells. Furthermore, iSLK cells infected wi...
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| Format: | Article |
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MDPI AG
2014-10-01
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| Series: | Viruses |
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| Online Access: | http://www.mdpi.com/1999-4915/6/10/4005 |
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| author | Karlie Plaisance-Bonstaff Hong Seok Choi Tyler Beals Brian J. Krueger Isaac W. Boss Lauren A. Gay Irina Haecker Jianhong Hu Rolf Renne |
| author_facet | Karlie Plaisance-Bonstaff Hong Seok Choi Tyler Beals Brian J. Krueger Isaac W. Boss Lauren A. Gay Irina Haecker Jianhong Hu Rolf Renne |
| author_sort | Karlie Plaisance-Bonstaff |
| collection | DOAJ |
| description | Kaposi’s sarcoma-associated herpesvirus (KSHV) microRNAs are encoded in the latency-associated region. Knockdown of KSHV miR-K12-3 and miR-K12-11 increased expression of lytic genes in BC-3 cells, and increased virus production from latently infected BCBL-1 cells. Furthermore, iSLK cells infected with miR-K12-3 and miR-K12-11 deletion mutant viruses displayed increased spontaneous reactivation and were more sensitive to inducers of reactivation than cells infected with wild type KSHV. Predicted binding sites for miR-K12-3 and miR-K12-11 were found in the 3’UTRs of the cellular transcription factors MYB, Ets-1, and C/EBPα, which activate RTA, the KSHV replication and transcription activator. Targeting of MYB by miR-K12-11 was confirmed by cloning the MYB 3’UTR downstream from the luciferase reporter. Knockdown of miR‑K12-11 resulted in increased levels of MYB transcript, and knockdown of miR-K12-3 increased both C/EBPα and Ets-1 transcripts. Thus, miR-K12-11 and miR-K12-3 contribute to maintenance of latency by decreasing RTA expression indirectly, presumably via down‑regulation of MYB, C/EBPα and Ets-1, and possibly other host transcription factors. |
| first_indexed | 2024-04-13T12:29:12Z |
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| id | doaj.art-bdf30603e7324e6a8a1bfcf00d80b9f7 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-04-13T12:29:12Z |
| publishDate | 2014-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-bdf30603e7324e6a8a1bfcf00d80b9f72022-12-22T02:46:55ZengMDPI AGViruses1999-49152014-10-016104005402310.3390/v6104005v6104005KSHV miRNAs Decrease Expression of Lytic Genes in Latently Infected PEL and Endothelial Cells by Targeting Host Transcription FactorsKarlie Plaisance-Bonstaff0Hong Seok Choi1Tyler Beals2Brian J. Krueger3Isaac W. Boss4Lauren A. Gay5Irina Haecker6Jianhong Hu7Rolf Renne8Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610, USADepartment of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610, USADepartment of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610, USADepartment of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610, USADepartment of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610, USADepartment of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610, USADepartment of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610, USADepartment of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610, USADepartment of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610, USAKaposi’s sarcoma-associated herpesvirus (KSHV) microRNAs are encoded in the latency-associated region. Knockdown of KSHV miR-K12-3 and miR-K12-11 increased expression of lytic genes in BC-3 cells, and increased virus production from latently infected BCBL-1 cells. Furthermore, iSLK cells infected with miR-K12-3 and miR-K12-11 deletion mutant viruses displayed increased spontaneous reactivation and were more sensitive to inducers of reactivation than cells infected with wild type KSHV. Predicted binding sites for miR-K12-3 and miR-K12-11 were found in the 3’UTRs of the cellular transcription factors MYB, Ets-1, and C/EBPα, which activate RTA, the KSHV replication and transcription activator. Targeting of MYB by miR-K12-11 was confirmed by cloning the MYB 3’UTR downstream from the luciferase reporter. Knockdown of miR‑K12-11 resulted in increased levels of MYB transcript, and knockdown of miR-K12-3 increased both C/EBPα and Ets-1 transcripts. Thus, miR-K12-11 and miR-K12-3 contribute to maintenance of latency by decreasing RTA expression indirectly, presumably via down‑regulation of MYB, C/EBPα and Ets-1, and possibly other host transcription factors.http://www.mdpi.com/1999-4915/6/10/4005KSHVmiRNAlytic reactivationlatency |
| spellingShingle | Karlie Plaisance-Bonstaff Hong Seok Choi Tyler Beals Brian J. Krueger Isaac W. Boss Lauren A. Gay Irina Haecker Jianhong Hu Rolf Renne KSHV miRNAs Decrease Expression of Lytic Genes in Latently Infected PEL and Endothelial Cells by Targeting Host Transcription Factors Viruses KSHV miRNA lytic reactivation latency |
| title | KSHV miRNAs Decrease Expression of Lytic Genes in Latently Infected PEL and Endothelial Cells by Targeting Host Transcription Factors |
| title_full | KSHV miRNAs Decrease Expression of Lytic Genes in Latently Infected PEL and Endothelial Cells by Targeting Host Transcription Factors |
| title_fullStr | KSHV miRNAs Decrease Expression of Lytic Genes in Latently Infected PEL and Endothelial Cells by Targeting Host Transcription Factors |
| title_full_unstemmed | KSHV miRNAs Decrease Expression of Lytic Genes in Latently Infected PEL and Endothelial Cells by Targeting Host Transcription Factors |
| title_short | KSHV miRNAs Decrease Expression of Lytic Genes in Latently Infected PEL and Endothelial Cells by Targeting Host Transcription Factors |
| title_sort | kshv mirnas decrease expression of lytic genes in latently infected pel and endothelial cells by targeting host transcription factors |
| topic | KSHV miRNA lytic reactivation latency |
| url | http://www.mdpi.com/1999-4915/6/10/4005 |
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