Genome Wide siRNA Screen for Host Factors Required for Human Herpesvirus (HHV) Latency

Type of Award: Catalyst
Date Awarded: September 2012
Award End Date: August 2014
Amount Awarded: $ 200,000.00
PI(s): Richard Longnecker, PhD, NU; Lijun Rong, PhD, UIC; Bernard Roizman, ScD, UChicago;

Abstract: The proposed research focuses on two human herpes viruses (HHVs), herpes simplex 1 (HSV-1) and Epstein-Barr virus (EBV). These viruses represent divergent members of the HHV family that infect humans and cause a range of diseases that can be life threatening. The divergence in their gene content is reflected in their life-styles. Whereas HSV-1 establishes latency in neurons, causes encephalitis and is a major cause of blindness in USA, EBV establishes latency in white blood cells and is associated with a wide range of human cancers. In principle viruses depend and subvert cellular gene products to do the work for them. The focus of this proposal takes into account this fundamental finding and centers on two key questions: The first is what genes enable the two human herpes viruses to actively replicate at the site of initial infection yet remain silent (latency) for years at a time in neurons (HSV-1) or B cells (EBV). The second key question is what cellular genes are responsible for either establishment or termination of latent state. Because EBV and HSV-1 establish latency in very different cells, we hypothesize that these viruses will have commonalities and differences with the cellular genes that enable them to replicate in some cells and establish latent, silent infections in others. We propose to use highly efficient state of the art screening methods to identify the cellular genes that are required for regulating the latent phase of these two viruses. We predict that HSV-1 and EBV require both common and different cell factors for the latent life cycle phase. The identification of cellular genes required for establishment and maintenance will allow development of novel therapeutics effective against a broad range of human herpes viruses.