Author ORCID Identifier
https://orcid.org/0009-0006-9443-5831
Date of Award
Fall 10-5-2026
Document Type
Thesis (Ph.D.)
Department or Program
Microbiology and Immunology
First Advisor
David Leib
Abstract
Herpes simplex virus (HSV) infects sensory neurons that innervate mucosal
surfaces to establish infection in the human nervous system. The tissue tropism,
lifelong persistence, and frequent reactivation events implicate HSV infection in
neurodevelopmental and neurodegenerative disorders. Neonates are highly
susceptible to HSV because infection occurs during the intersection of an
immature immune system and rapid neurodevelopment. Even with timely
diagnosis and management neonatal HSV (nHSV) infections result in lifelong
morbidity and mortality. While the acute clinical outcomes of severe nHSV infection
are well documented, the consequences of such early-life infections on cognition
and behavior are poorly understood. We developed a low-dose intranasal HSV
infection model in neonatal mice to assess the neurologic morbidity and
pathological mechanism of occult infections in early-life. The low-dose infection did
not cause any acute symptoms yet led to permanent hypomyelination and
disordered remyelination within discrete brain regions. Once infected mice
reached adulthood, they contended with impaired learning and memory. To
establish and assess a HSV vaccination timeline for the prevention of acute and
persistent symptoms, we utilized the subclinical nHSV infection model with the
addition of a secondary infection during adulthood. Replication-defective HSV
immunizations provoked maternal immunity that was sufficient to prevent all
neurological outcomes and pathology following neonatal infection. However, the
presence of maternal antibodies prevented neonatal seroconversion, leaving the
offspring vulnerable to further infection once weaned. We therefore established a
pediatric immunization timepoint and prevented clinical symptoms following high-
dose reinfection in adulthood. The combination of maternal and pediatric
immunization was sufficient to protect against HSV infection during critical
neurodevelopmental and neurodegenerative periods. These data provide a refined
approach for future HSV vaccine clinical trials and, through a novel mechanism of
early-life viral-induced neurologic damage, inform therapeutic research to support
cognitive health.
Original Citation
Dutton AJ, Turnbaugh EM, Patel CD, Garland CR, Taylor SA, Alers-
Velazquez R, et al. Asymptomatic neonatal herpes simplex virus infection in
mice leads to persistent CNS infection and long-term cognitive impairment.
PLOS Pathog. 2025 Feb 7;21(2):e1012935. doi:10.1371/journal.ppat.1012935
Recommended Citation
Turnbaugh, Evelyn Marshall, "Etiology and Prevention of Cognitive Dysfunction following Neonatal Herpes Simplex Virus Infection" (2026). Dartmouth College Ph.D Dissertations. 566.
https://digitalcommons.dartmouth.edu/dissertations/566
