Characterizing Herpes Simplex Virus Type 1 Replication Kinetics, Latency, and Reactivation in the Lip Scarification Model of Infection and Disease

Abstract

Herpes simplex virus type 1 (HSV-1) is a common human pathogen which infects the majority of adults. The virus establishes a lifelong latent infection in sensory neurons and periodically reactivates to cause recurrent disease. Most new human infections above the neck occur in the lower lip but most animal models of HSV-1 infections do not inoculate through the lip. Here we describe the acute and latent infection events of HSV-1 infections in a lip model of HSV-1 infection and disease. Mice exhibited clinical lesions and pathology consistent with human HSV-1 infections. Mice were able to clear the primary infection, establish latency, and the resultant latently infected tissue was capable of supporting viral reactivation. This HSV-1 infection system was subsequently used to perform initial testing of a novel CRISPR/Cas9 gene editing therapeutic. Overall, these studies have established the basic events of acute and latent infection as well as viral reactivation in mice infected via a lip inoculation. In addition, these studies have shown the utility of the lip scarification and HSV-1 infection and disease model to study molecular pathogenic events associated with the establishment, maintenance, and reactivation of latent infection and associated disease processes. This model can be used for testing a variety of therapeutics for efficacy with respect to reducing viral replication and pathology in the lip and to minimize or eliminate acute HSV-1 infection and/or remove latent viral genomes in order to develop a cure for viral reactivation and recurrent HSV-1 infections.%%%%Ph.D., Microbiology and Immunology – Drexel University, 2016