Staudt Michelle R, Dittmer Dirk P
Department of Microbiology and Immunology and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, 804 Mary Ellen Jones, CB#7290, Chapel Hill, NC 27599-7290, USA.
Virology. 2006 Jun 20;350(1):192-205. doi: 10.1016/j.virol.2006.03.006. Epub 2006 Apr 17.
Latent transcription of the latency-associated nuclear antigen (LANA/ORF73) of Kaposi's sarcoma-associated herpesvirus is driven by the LANAp-c. Complexity arises during lytic reactivation, however, as the bicistronic K14/vGPCR transcript initiates 32 bp downstream of LANAp-c in the opposite orientation. We identify an Rta/ORF50-inducible LANA promoter (LANAp-i) that is distinct from the LANAp-c. LANAp-c is unaffected by Rta/ORF50. Utilization of the second, downstream LANAp-i explains how LANA and K14/vGPCR are simultaneously transcribed during de novo infection or lytic reactivation. Transactivation of LANAp-i and K14/vGPCRp requires the C-terminal activation domain of Rta/ORF50 and is mediated by DNA-binding-dependent and -independent Rta/ORF50 mechanisms. Transcriptional profiling following viral reactivation support promoter reporter phenotypes. In sum, cis-elements within the LANAp were selected to ensure faithful expression of LANA and other genes regulated by LANAp during all stages of the KSHV lifecycle despite potential interference from K14/vGPCRp activity.
卡波西肉瘤相关疱疹病毒的潜伏相关核抗原（LANA/ORF73）的潜伏转录由LANAp-c驱动。然而，在裂解性再激活过程中出现了复杂性，因为双顺反子K14/vGPCR转录本以相反方向在LANAp-c下游32 bp处起始。我们鉴定出一种与LANAp-c不同的Rta/ORF50诱导型LANA启动子（LANAp-i）。LANAp-c不受Rta/ORF50影响。利用第二个下游的LANAp-i解释了在初次感染或裂解性再激活期间LANA和K14/vGPCR如何同时转录。LANAp-i和K14/vGPCRp的反式激活需要Rta/ORF50的C末端激活结构域，并由依赖于DNA结合和不依赖于DNA结合的Rta/ORF50机制介导。病毒再激活后的转录谱分析支持启动子报告基因表型。总之，尽管存在K14/vGPCRp活性的潜在干扰，但LANAp内的顺式元件被选择以确保在卡波西肉瘤相关疱疹病毒生命周期的所有阶段中LANA和其他受LANAp调控的基因的忠实表达。
