The PI proposes to elucidate the pharmacological and molecular mechanisms that underlie reactivation of latent HSV from trigeminal ganglia (TG). A variety of studies involving HSV DNA and the RNAs designated as latency-associated transcripts (LAT) will be done using animal models of HSV reactivation.
The specific aims are 1) to determine the relationship between specific sequence elements in the LAT promoter and the mechanisms that govern the ability to undergo in vivo adrenergic reactivation; 2) to detect and quantitate HSV transcripts in he TG from animals harboring latent viruses that exhibit different phenotypes and genotypes before and after adrenergic reactivation; and 3) to characterize the pharmacological and molecular mechanisms involved in propranolol inhibition of in vivo reactivation in animals harboring latent viruses that exhibit different phenotypes and genotypes. The methodology includes iontophoresis of epinephrine and hyperthermia to induce HSV reactivation, slit-lamp examination to detect spontaneous corneal epithelial lesions, sequence analysis of LAT regions of HSV DNA, detection of HSV DNA methylation, and RT- PCR to quantitate HSV RNAs. The long-term goal is to provide insights into HSV pathogenesis that could result in the development of therapeutic strategies to block neuronal HSV reactivation and the morbidity caused by repeated episodes of herpetic disease.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY006311-13
Application #
2882877
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1985-07-01
Project End
2002-02-28
Budget Start
1999-03-01
Budget End
2000-02-29
Support Year
13
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Louisiana State University Hsc New Orleans
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
782627814
City
New Orleans
State
LA
Country
United States
Zip Code
70112
Alexandrov, Peter N; Pogue, Aileen I; Lukiw, Walter J (2018) Synergism in aluminum and mercury neurotoxicity. Integr Food Nutr Metab 5:
Alexandrov, P N; Percy, M E; Lukiw, Walter J (2018) Chromosome 21-Encoded microRNAs (mRNAs): Impact on Down's Syndrome and Trisomy-21 Linked Disease. Cell Mol Neurobiol 38:769-774
Alexandrov, Peter N; Zhao, Yuhai; Jaber, Vivian et al. (2017) Deficits in the Proline-Rich Synapse-Associated Shank3 Protein in Multiple Neuropsychiatric Disorders. Front Neurol 8:670
Zhao, Yuhai; Cong, Lin; Jaber, Vivian et al. (2017) Microbiome-Derived Lipopolysaccharide Enriched in the Perinuclear Region of Alzheimer's Disease Brain. Front Immunol 8:1064
Zhao, Yuhai; Cong, Lin; Lukiw, Walter J (2017) Lipopolysaccharide (LPS) Accumulates in Neocortical Neurons of Alzheimer's Disease (AD) Brain and Impairs Transcription in Human Neuronal-Glial Primary Co-cultures. Front Aging Neurosci 9:407
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Pogue, A I; Jaber, V; Zhao, Y et al. (2017) Systemic Inflammation in C57BL/6J Mice Receiving Dietary Aluminum Sulfate; Up-Regulation of the Pro-Inflammatory Cytokines IL-6 and TNF?, C-Reactive Protein (CRP) and miRNA-146a in Blood Serum. J Alzheimers Dis Parkinsonism 7:
Zhao, Yuhai; Jaber, Vivian; Percy, Maire E et al. (2017) A microRNA cluster (let-7c, miRNA-99a, miRNA-125b, miRNA-155 and miRNA-802) encoded at chr21q21.1-chr21q21.3 and the phenotypic diversity of Down's syndrome (DS; trisomy 21). J Nat Sci 3:
Zhao, Yuhai; Jaber, Vivian; Lukiw, Walter J (2017) Secretory Products of the Human GI Tract Microbiome and Their Potential Impact on Alzheimer's Disease (AD): Detection of Lipopolysaccharide (LPS) in AD Hippocampus. Front Cell Infect Microbiol 7:318
Zhao, Yuhai; Jaber, Vivian; Lukiw, Walter J (2016) Over-Expressed Pathogenic miRNAs in Alzheimer's Disease (AD) and Prion Disease (PrD) Drive Deficits in TREM2-Mediated A?42 Peptide Clearance. Front Aging Neurosci 8:140

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