A primary infection with herpes simplex virus (HSV) results in disease ranging from mild oral or genital lesions to more significant keratoconjunctivitis, congenital-derived blindness-neurological issues, or viral encephalitis. Most significantly, infection results in the establishment of lifelong persistence of the viral genomes in neurons of sensory ganglia. Periodically these latent genomes undergo reactivation or re-entry to the lytic replication cycle that results in subclinical shedding of viral progeny or produce clinical recurrent disease.
HSV lytic infection is characterized by a highly ordered cascade of gene expression. The initial stage, expression of the viral Immediate Early (IE) genes, is a critical determinant of the outcome of infection and these genes are regulated by complex combinatorial mechanisms that couple viral and cellular activators-coactivators. The Kristie laboratory focuses on the components and biochemical mechanisms involved in determining viral IE gene expression in the context of the dynamic interplay between the virus and host cell. Particular focus points are the involvement of cellular transcriptional activators-coactivators in viral IE gene expression (i.e. HCF-1), the regulatory impacts of chromatin on viral gene expression, and the mechanisms involved in viral interface-modulation of cellular chromatin machinery.