A critical Sp1 element in the rhesus rhadinovirus (RRV) Rta promoter confers high-level activity that correlates with cellular permissivity for viral replication

• Published in: Virology (New York, N.Y.) Vol. 448; pp. 196 - 209
• Main Authors: DeMaster, Laura K, Rose, Timothy M
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 05.01.2014
• Subjects: Amino Acid Sequence; Animals; Cell Line; Gene Expression Regulation, Viral; Herpesviridae Infections - genetics; Herpesviridae Infections - metabolism; Herpesviridae Infections - veterinary; Herpesviridae Infections - virology; Herpesvirus 8, Human - chemistry; Herpesvirus 8, Human - genetics; Herpesvirus 8, Human - metabolism; Humans; Immediate-Early Proteins - chemistry; Immediate-Early Proteins - genetics; Immediate-Early Proteins - metabolism; Infectious Disease; Kaposi's sarcoma-associated herpesvirus; KSHV; Macaca; Macaca mulatta; Macaque; Molecular Sequence Data; Primate Diseases - genetics; Primate Diseases - metabolism; Primate Diseases - virology; Promoter; Promoter Regions, Genetic; Protein Binding; Replication; Response Elements; Rhadinovirus; Rhadinovirus - genetics; Rhadinovirus - physiology; RRV; Rta; Sequence Alignment; Sp1; Sp1 Transcription Factor - genetics; Sp1 Transcription Factor - metabolism; Trans-Activators - chemistry; Trans-Activators - genetics; Trans-Activators - metabolism; Transactivator; Viral Proteins - chemistry; Viral Proteins - genetics; Viral Proteins - metabolism; Virus Replication; Promoter; KSHV; Sp1; RRV; Replication; Macaque; Transactivator; Rhadinovirus; Rta
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2013.10.013

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.