An Assessment of Viral Population Diversity in Herpes Simplex Virus 1 Clinical Samples From Infected NeonatesPassetti, Holly herpes simplex virus 1HSV-1neonatal infectionintrastrain diversityinterhost diversityintrahost diversityviral culturecellular assaysviral comparative genomicsclinical samplesacyclovirantiviralsacyclovir resistancewhole-genome viral sequencingminor variantsviral population diversitycoinfectionmixed infectionBiochemistry, Microbiology, and Molecular BiologyPHDHerpes simplex virus (HSV) is a highly prevalent human pathogen, with herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) infecting approximately 70% and 11% of the global population, respectively. Traditionally HSV-1 was thought to occupy the oral niche, while HSV-2 infected the genital niche. However, in recent years, there has been an increase in the number of new-onset HSV-1 genital infections due to changes in social and sexual behaviors. This has led to an increased incidence of neonatal HSV-1 infections compared to HSV-2. Neonatal HSV infections are defined as infection with the virus in the first 28 days of life and pose a clinical challenge. More than half (55%) of neonates develop a severe invasive form of disease involving infection of the internal organs and/or central nervous system. HSV-1 establishes a chronic infection in its host, due to its lytic and latent lifecycles, contributing to neurodevelopmental delays and other morbidities in this fragile population. Currently, there is no rationale for the disproportionate disease severity experienced by neonates. In this thesis, I explore the standing genetic and phenotypic diversity in HSV-1 clinical samples obtained from infected neonates. In conjunction with this, I also examine how selective pressures, such as antivirals, affect the viral population and investigate the limits of current sequencing technologies on potential mixed populations or coinfections. This work has expanded our understanding into the between- and within-host diversity existing in the neonatal population, the propensity and dynamics of developing antiviral resistance, and the complexity of coinfection identification through next-generation sequencing. These findings suggest future research is needed in HSV-1 viral population dynamics and evolution in the neonatal host to enhance our understanding of the viral contribution to disease severity.Santhosh Girirajan, Program Head/ChairMoriah Szpara, Chair & Dissertation AdvisorTroy Sutton, Outside Unit MemberSanthosh Girirajan, Major Field MemberJoyce Jose, Major Field MemberDavid Kennedy, Outside Field MemberLisa Akhtar, Special Memberrestricted_to_institution2026-07-14T14:32:03Zhttps://etda.libraries.psu.edu/catalog/25515hap5160