Viral reprogramming of host transcription initiation

Nathan A. Ungerleider, Tulane Cancer Center, New Orleans, LA
Claire Roberts, Tulane Cancer Center, New Orleans, LA
Tina M. O'Grady, Tulane Cancer Center, New Orleans, LA
Trang T. Nguyen, Tulane Cancer Center, New Orleans, LA
Melody Baddoo, Tulane Cancer Center, New Orleans, LA
Jia Wang, Tulane Cancer Center, New Orleans, LA
Eman Ishaq, Tulane Cancer Center, New Orleans, LA
Monica Concha, Tulane Cancer Center, New Orleans, LA
Meggie Lam, Tulane Cancer Center, New Orleans, LA
Jordan Bass, Tulane Cancer Center, New Orleans, LA
Truong D. Nguyen, Tulane Cancer Center, New Orleans, LA
Nick Van Otterloo, Tulane Cancer Center, New Orleans, LA
Nadeeshika Wickramarachchige-Dona, Tulane Cancer Center, New Orleans, LA
Dorota Wyczechowska, LSU Health Sciences Center - New Orleans
Maria Morales, Tulane Cancer Center, New Orleans, LA
Tianfang Ma, Dana-Farber Cancer Institute, Boston, MA
Yan Dong, Tulane Cancer Center, New Orleans, LA
Erik K. Flemington, Tulane Cancer Center, New Orleans, LA

Abstract

Viruses are master remodelers of the host cell environment in support of infection and virus production. For example, viruses typically regulate cell gene expression through modulating canonical cell promoter activity. Here, we show that Epstein Barr virus (EBV) replication causes 'de novo' transcription initiation at 29674 new transcription start sites throughout the cell genome. De novo transcription initiation is facilitated in part by the unique properties of the viral pre-initiation complex (vPIC) that binds a TATT[T/A]AA, TATA box-like sequence and activates transcription with minimal support by additional transcription factors. Other de novo promoters are driven by the viral transcription factors, Zta and Rta and are influenced by directional proximity to existing canonical cell promoters, a configuration that fosters transcription through existing promoters and transcriptional interference. These studies reveal a new way that viruses interact with the host transcriptome to inhibit host gene expression and they shed light on primal features driving eukaryotic promoter function.