期刊
VIROLOGY
卷 379, 期 2, 页码 234-244出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2008.06.043
关键词
KSHV; LANA; viral latency; lytic replication; vital transcriptional program; reverse genetics
类别
资金
- National Institute of Health [CA096512, CA124332, CA119889, DE017333]
- American Cancer Society Research Scholar [RSG-04-195]
Following primary infection, KSHV establishes a lifelong Persistent latent infection in the host. The mechanism of KSHV latency is not fully understood. The latent nuclear antigen (LANA or LNA) encoded by ORF73 is one of a few vital genes expressed during KSHV latency, and is consistently detected in all KSHV-related malignancies. LANA is essential for KSHV episome persistence, and regulates the expression of viral lytic genes through epigenetic silencing, and inhibition of the expression and transactivation function of the key KSHV lytic replication initiator RTA (ORF50). In this Study, we used a genetic approach to examine the role of LANA in regulating KSHV lytic replication program. Deletion of LANA did not affect the expression of its adjacent genes vCyclin (ORF72) and vFLIP (ORF71). In contrast, the expression levels of viral lytic genes including immediate-early gene RTA, early genes MTA (ORF57), vIL-6 (ORF-K2) and ORF59, and late gene ORF-K8.1 were increased before and after vital lytic induction with 12-O-tetradecanoyl-phorbol-13-acetate and sodium butyrate. This enhanced expression of vital lytic genes was also observed following overexpression of RTA with or without Simultaneous chemical induction. Consistent with these results, the LANA mutant cells produced more infectious virions than the wild-type virus cells did, Furthermore, genetic repair of the mutant Virus reverted the phenotypes to those of wild-type virus. Together, these results have demonstrated that, in the context of vital genome, LANA contributes to KSHV latency by regulating the expression of RTA and its downstream genes. (C) 2008 Elsevier Inc. All rights reserved.
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