Autor: |
Karlie Plaisance-Bonstaff, Hong Seok Choi, Tyler Beals, Brian J. Krueger, Isaac W. Boss, Lauren A. Gay, Irina Haecker, Jianhong Hu, Rolf Renne |
Jazyk: |
angličtina |
Rok vydání: |
2014 |
Předmět: |
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Zdroj: |
Viruses, Vol 6, Iss 10, Pp 4005-4023 (2014) |
Druh dokumentu: |
article |
ISSN: |
1999-4915 |
DOI: |
10.3390/v6104005 |
Popis: |
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. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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