Honors Theses
Date of Award
5-2024
Document Type
Undergraduate Thesis
Degree Name
BS
Department
Biomedical Sciences
Faculty Mentor
Robert A. Barrington
Advisor(s)
Alison Henry, Phoibe Renema
Abstract
Cleavage of amyloid precursor protein (APP) generates the antimicrobial peptide amyloid beta (Aβ), the accumulation of which is linked to Alzheimer’s Disease (AD) pathogenesis. Whether processing of APP contributes to anti-viral responses is debated. Herpes Simplex Virus Type 1 (HSV-1), a neurotropic double-stranded deoxyribonucleic acid (DNA) virus, establishes lifelong latency and can cause a range of outcomes, from asymptomatic infection to herpetic encephalitis (HSE). Whether disparate outcomes are dependent on HSV-1 strain is unknown. Using three differentially virulent HSV-1 strains, we compared the regulation of APP-associated proteolytic processing in both a corneal infection murine model and an in vitro model. By single-cell RNA-sequencing on infected cornea, and by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) on infected corneal fibroblasts, we observed that transcripts of APP, presenilin-1 (PSEN-1), and γ-secretase activating protein (GSAP) were elevated in less neurovirulent strains of HSV-1 relative to the most neurovirulent strain. Furthermore, processing of APP to Aβ was increased in cells infected with less neurovirulent HSV-1. Taken together, these data are consistent with a model whereby APP production and processing shapes neurovirulence of HSV-1.
Recommended Citation
Elias, Mia, "Cell Type-Specific Production of Amyloid Precursor Protein During Infection is Dependent on the Strain of Herpes Simplex Virus 1" (2024). Honors Theses. 49.
https://jagworks.southalabama.edu/honors_college_theses/49
Comments
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