title: A critical Sp1 element in the rhesus rhadinovirus (RRV) Rta promoter confers high-level activity that correlates with cellular permissivity for viral replication.
abstract: 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.
authors: 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. Electronic address: demaster@mail.med.upenn.edu.
authors: Laura K
authors: LK
authors: DeMaster
authors: Timothy M
authors: TM
authors: Rose
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D015967:Gene Expression Regulation, Viral; D006566:Herpesviridae Infections / Q000235:genetics / Q000378:metabolism / Q000662:veterinary* / Q000821:virology; D019288:Herpesvirus 8, Human / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D017874:Immediate-Early Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D018419:Primate Diseases / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D020218:Response Elements; D018144:Rhadinovirus / Q000235:genetics / Q000502:physiology*; D016415:Sequence Alignment; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D014779:Virus Replication
chemical_list: D017874:Immediate-Early Proteins; C417604:Rta protein, Human herpesvirus 8; D016329:Sp1 Transcription Factor; D015534:Trans-Activators; D014764:Viral Proteins
keywords: KSHV; Macaque; Promoter; RRV; Replication; Rhadinovirus; Rta; Sp1; Transactivator