Project 171759

Adenovirus is a common virus that causes mild illness in most patients, primarily respiratory disease, but can be lethal in immunocompromised individuals, or pediatric and geriatric populations. Currently, there are no effective treatments to combat infection with this virus. Adenovirus has evolved to very effectively take-over the host cell and redirect all cellular processes to the production of new viruses. To accomplish this, soon after entering the host cell, the virus must begin to efficiently express genes from the incoming viral DNA that are necessary for co-opting cellular functions. Little is known about the structure of the viral DNA within the infected cell: whether it is wrapped in cellular proteins, called histones, that are crucial for expression and regulation of normal cellular genes was unknown. Our recent studies have shown that in the infected cell the viral DNA is wrapped in histones, and that this event is necessary for efficient expression of viral genes. We will now expand these studies to determine the cellular proteins that are involved in depositing histones on the Ad DNA, and the impact this event has on virus replication and growth. Our studies may identify new targets for therapeutic intervention, which will lessen the impact of Ad-induced disease and virus spread.