An Assessment of Viral Population Diversity in Herpes Simplex Virus 1 Clinical Samples From Infected Neonates

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Author:
Passetti, Holly
Graduate Program:
Biochemistry, Microbiology, and Molecular Biology
Degree:
Doctor of Philosophy
Document Type:
Dissertation
Date of Defense:
July 13, 2026
Committee Members:
Santhosh Girirajan, Program Head/Chair
Moriah Szpara, Chair & Dissertation Advisor
Troy Sutton, Outside Unit Member
Santhosh Girirajan, Major Field Member
Joyce Jose, Major Field Member
David Kennedy, Outside Field Member
Lisa Akhtar, Special Member
Keywords:
herpes simplex virus 1
HSV-1
neonatal infection
intrastrain diversity
interhost diversity
intrahost diversity
viral culture
cellular assays
viral comparative genomics
clinical samples
acyclovir
antivirals
acyclovir resistance
whole-genome viral sequencing
minor variants
viral population diversity
coinfection
mixed infection
Abstract:
Herpes 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.