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.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Visual Sciences A Study Section (VISA)
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Louisiana State University Hsc New Orleans
Schools of Medicine
New Orleans
United States
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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
Jaber, V; Zhao, Y; Lukiw, W J (2017) Alterations in micro RNA-messenger RNA (miRNA-mRNA) Coupled Signaling Networks in Sporadic Alzheimer's Disease (AD) Hippocampal CA1. J Alzheimers Dis Parkinsonism 7:
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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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