Mechanisms of cytomegalovirus regulation of neurodegenerative markers

dc.contributor.advisorHanson, Laura K.
dc.contributor.advisorHynds, DiAnna L.
dc.creatorMody, Prapti
dc.date.accessioned2019-11-13T15:01:17Z
dc.date.available2019-11-13T15:01:17Z
dc.date.created2019-08
dc.date.issued9/9/2019
dc.date.submitted19-Aug
dc.date.updated2019-11-13T15:01:18Z
dc.description.abstractAlzheimer’s disease (AD) manifests with loss of neurons associated with intercellular amyloid plaques made up of amyloid beta peptides (Aβ) and intracellular neurofibrillary tangles of hyperphosphorylated tau proteins. Normally, Aβ peptides function as cell signaling molecules and can mediate antimicrobial activity. Tau is one of the microtubule stabilizing proteins in cells and its expression and post-translational modifications depend upon cell type and cell age. Despite testing many therapeutics designed to target abnormal amyloid or tau, there is no sustained treatment. Current research is therefore focused on early steps in production of dysfunctional amyloid and tau11, however, there are relatively few strong established models for these studies. Previous researchers have shown that some herpesvirus infections can alter amyloid and tau in ways similar to that seen in AD. There is clinical correlation between herpesvirus infection and higher risk of AD. Herpes simplex virus 1 can interact with amyloid precursor protein (APP) and affect tau v hyperphosphorylation. Based on these findings, we hypothesized that MCMV infection could be a useful model if it similarly impacted AD markers. We found that APP was upregulated in MCMV-infected fibroblasts and viral late gene products were required. Levels of processing enzymes (secretases) and one cleavage product (Aβ42) were unchanged. The activity of β-secretase was not increased. There was no similar APP induction in RCN. Thus, CMV may have cell-type or species-based differences for effects on the amyloid pathway. Levels of total tau and tau phosphorylated at S396 were increased in MCMV-infected fibroblasts and neurons. This also required viral late gene products. There was no change in tau phosphorylation at S202 or GSK3β levels. We used lithium chloride (LiCl) to inhibit activity of GSK3. Although MCMV infection was inhibited, the banding patterns for tau and phospho-tau (S396) exhibited minor alterations when LiCl was added at the time that changes started. Thus, other kinases are more likely important. We have confirmed that MCMV can induce AD markers. This is useful for using MCMV infection in AD animal models for elucidation of early steps, promising for testing novel preventives for these changes, and for developing novel antivirals.
dc.format.mimetypeapplication/pdf
dc.identifier.urihttps://hdl.handle.net/11274/11983
dc.language.isoen
dc.subjectCytomegalovirus
dc.subjectAlzheimer's disease
dc.subjectHerpes virus
dc.subjectNeurodegenerative disease
dc.subjectNeurodegeneration
dc.titleMechanisms of cytomegalovirus regulation of neurodegenerative markers
dc.typeThesis
dc.type.materialtext
thesis.degree.departmentBiology
thesis.degree.disciplineMolecular Biology
thesis.degree.grantorTexas Woman's University
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy

Files

Original bundle

Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
MODY-DISSERTATION-2019.pdf
Size:
2.87 MB
Format:
Adobe Portable Document Format

License bundle

Now showing 1 - 2 of 2
No Thumbnail Available
Name:
LICENSE.txt
Size:
1.84 KB
Format:
Plain Text
Description:
No Thumbnail Available
Name:
PROQUEST_LICENSE.txt
Size:
5.84 KB
Format:
Plain Text
Description: