Department of Global Health, University of Washington, Seattle, WA 98195, USA; Center for Childhood Infections and Prematurity Research, Seattle Children's Research Institute, Seattle, WA 98101, USA.
Virology. 2014 Jan 5;448:196-209. doi: 10.1016/j.virol.2013.10.013. Epub 2013 Oct 29.
KSHV establishes characteristic latent infections in vitro, while RRV, a related macaque rhadinovirus, establishes characteristic permissive infections with virus replication. We identified cells that are not permissive for RRV replication and recapitulate the latent KSHV infection and reactivation processes. The RRV replication and transactivator (Rta) promoter was characterized in permissive and non-permissive cells and compared to the KSHV Rta promoter. Both promoters contained a critical Sp1 element, had equivalent activities in different cell types, and were inhibited by LANA. RRV and KSHV infections were non-permissive in cells with low Rta promoter activity. While RRV infections were permissive in cells with high basal promoter activity, KSHV infections remained non-permissive. Our studies suggest that RRV lacks the Rta-inducible LANA promoter that is responsible for LANA inhibition of the KSHV Rta promoter and induction of latency during KSHV infection. Instead, the outcome of RRV infection is determined by host factors, such as Sp1.
KSHV 在体外建立特征性潜伏感染，而 RRV，一种相关的猕猴疱疹病毒，则建立具有病毒复制的特征性许可感染。我们鉴定了不允许 RRV 复制的细胞，并重新模拟了潜伏的 KSHV 感染和再激活过程。在许可和非许可细胞中对 RRV 复制和转录激活剂（Rta）启动子进行了表征，并与 KSHV Rta 启动子进行了比较。两个启动子都含有一个关键的 Sp1 元件，在不同的细胞类型中具有相同的活性，并且都被 LANA 抑制。在 Rta 启动子活性低的细胞中，RRV 和 KSHV 感染都不允许。虽然 RRV 感染在基础启动子活性高的细胞中是允许的，但 KSHV 感染仍然不允许。我们的研究表明，RRV 缺乏 Rta 诱导的 LANA 启动子，该启动子负责 LANA 抑制 KSHV Rta 启动子并在 KSHV 感染期间诱导潜伏。相反，RRV 感染的结果取决于宿主因素，如 Sp1。
