Latent herpes simplex virus type 1 in normal and Alzheimer's disease brains

Jamieson, Gordon A.; Maitland, Norman J.; Wilcock, Gordon; Craske, J.; Itzhaki, Ruth F.

doi:10.1002/jmv.1890330403

Cited by 267 publications

(181 citation statements)

References 16 publications

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“…This finding suggests that mechanical stimulation is not sufficient to induce stromal inflammation. The paradox that apoE4 alone is not sufficient to cause disease (Poirier et al, 1993) is also true for the risk factor association of HSV-1 to AD (Ball, 1982;Jamieson et al, 1991;Poirier et al, 1993) and cold sores (herpes labialis) (Lin et al, 1995;.…”

Section: Discussionmentioning

confidence: 99%

Effect of human apolipoprotein E genotype on the pathogenesis of experimental ocular HSV-1

Bhattacharjee

Neumann

Foster

et al. 2008

Experimental Eye Research

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The isoform-specific role of human apolipoprotein E (apoE) has been assessed in a mouse model of ocular herpes. Female, age-matched transgenic mice knocked-in for the human allele apoE3 or apoE4 and their parent C57Bl/6 mice were inoculated corneally with HSV-1 strain KOS. Ocular HSV-1 pathogenesis was monitored through viral replication and clinical progression of stromal opacity and neovascularization by slit-lamp examination. Establishment of latency was determined by analysis of HSV-1 DNA (copy number) by specific real-time PCR in the cornea, trigeminal ganglia (TG), and brain. Representative groups of transgenic mice were sacrificed for the analysis of gene expression of vascular endothelial growth factor (VEGF) by reverse-transcription PCR, and apoE expression by Western blot analysis. At 6 days post-infection (P.I.), the ocular infectious HSV-1 titer was significantly higher (p < 0.05) in apoE4 mice compared with apoE3 and C57Bl/6 mice. Corneal neovascularization in apoE4 mice was significantly higher (p < 0.05) than apoE3 and C57Bl/6 mice. The onset of corneal opacity in apoE4 mice was accelerated during days 9--11 P.I.; however, no significant difference in severity was seen on P.I. days 15 and beyond. At 28 days P.I., infected mice of all genotypes had no significant differences in copy numbers (range 0--15) of HSV-1 DNA in their corneas, indicating that HSV-1 DNA copy numbers in cornea are independent of apoE isoform regulation. At 28 days P.I., both apoE4 and C57Bl/6 mice had a significantly higher (p = 0.001) number of copies of HSV-1 DNA in TG compared with apoE3. ApoE4 mice also had significantly higher (p = 0.001) copies of HSV-1 DNA in their TGs compared with C57Bl/6 mice. In brain, both apoE4 and C57Bl/6 mice had significantly higher numbers (p ≤ 0.03) of copies of HSV-1 DNA compared with apoE3 mice. However, the number of HSV-1 DNA copies in the brain of C57Bl/6 mice was not significantly different than that of apoE4 (p = 0.1). Comparative molecular analysis between apoE3 and apoE4 mice on selected days between 7 and 28 P.I., inclusive, revealed that the corneas of apoE4 mice expressed VEGF. None of the corneas in the apoE3 mice expressed VEGF Corresponding author: James M. Hill, Ph.D., LSU Eye Center, 2020 Gravier Street, Suite B, New Orleans, LA 70112, USA, Telephone: (504) 568 2274, Fax: (504) 568 2385, E-mail: jhill@lsuhsc.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Western blot analysis showed proteolytic cleavage of the apoE protein in the corneas of the apoE4 mice. Through days 14 to 28 P.I., a ~29 kDa C-terminal truncated apoE f...

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Section: Discussionmentioning

confidence: 99%

Effect of human apolipoprotein E genotype on the pathogenesis of experimental ocular HSV-1

Bhattacharjee

Neumann

Foster

et al. 2008

Experimental Eye Research

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“…[92][93][94] While patients rarely exhibit signs of encephalitis, many postmortem studies find a high prevalence of HSV-1 in the brain. [95][96][97][98] Strikingly, Alzheimer disease brains contain a high localization of HSV-1 DNA within amyloid plaques, 72% in AD patients, whereas only 24% of the DNA associates with plaques in agematched non-AD patients, who accumulate plaques at a much lower rate. 7 Furthermore, animal models and acute HSV-1 encephaltitis patients show that the virus targets brain regions overlapping with AD: frontal and temporal cortices and the hippocampus.…”

Section: Hsv-1-associated Autophagy Dysfunction: a Risk Factor For Nementioning

confidence: 99%

Autophagy interaction with herpes simplex virus type-1 infection

O’Connell

Liang

2016

Autophagy

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More than 50% of the U.S. population is infected with herpes simplex virus type-I (HSV-1) and global infectious estimates are nearly 90%. HSV-1 is normally seen as a harmless virus but debilitating diseases can arise, including encephalitis and ocular diseases. HSV-1 is unique in that it can undermine host defenses and establish lifelong infection in neurons. Viral reactivation from latency may allow HSV-1 to lay siege to the brain (Herpes encephalitis). Recent advances maintain that HSV-1 proteins act to suppress and/or control the lysosome-dependent degradation pathway of macroautophagy (hereafter autophagy) and consequently, in neurons, may be coupled with the advancement of HSV-1-associated pathogenesis. Furthermore, increasing evidence suggests that HSV-1 infection may constitute a gradual risk factor for neurodegenerative disorders. The relationship between HSV-1 infection and autophagy manipulation combined with neuropathogenesis may be intimately intertwined demanding further investigation.

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“…Todos estos hallazgos, y considerando que a nivel del SNC HSV-1 puede establecer latencia en áreas frontal, temporal e hipocampo 56,57 , sugieren que HSV-1 podría estar implicado en la inducción de eventos neuropatológicos reiterados a lo largo de la vida, pudiendo constituir un riesgo de disfunción neuronal en esta zona del SNC asociada con memoria y capacidades cognitivas.…”

Section: Hsv-1 Como Factor De Riesgo Asociado Con La Enfermedad De Alunclassified

Herpes simplex virus tipo 1 como factor de riesgo asociado con la enfermedad de Alzheimer

et al. 2011

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Herpes simplex virus tipo 1 L a familia Herpesviridae, se encuentra ampliamente diseminada en la naturaleza. Existen más de 100 tipos diferentes de herpesvirus, los que presentan la misma estructura, ADN lineal de doble hebra dentro de una cápside icosaédrica, rodeada por un tegumento proteico y cubierto por una envoltura lipídica (Figura 1) 1,2 . Una característica que distingue a los herpesvirus, es su capacidad para establecer infecciones persistentes latentes en el hospedero infectado, estado en el cual el genoma viral se encuentra en forma episomal en el núcleo de la célula infectada, con una expresión limitada de genes específi cos para el mantenimiento del estado de latencia (transcritos LAT) y sin producir partículas virales infectivas 3,4 . Este tipo de infección se piensa que constituye una estrategia viral para evadir su detección por parte del sistema inmune. Bajo ciertas condiciones -incluyendo la exposición a radiación UV, estrés emocional, alteración del balance hormonal, depresión del sistema inmunológico, entre otros-se puede interrumpir el estado de latencia, induciendo una reactivación del genoma viral, con la consecuente producción de nuevas partículas virales infectivas que inician la recurrencia del cuadro clínico 1,4 . Sin embargo, los mecanismos celulares y moleculares de este proceso, aún se desconocen en detalle.En base al tipo de célula en que establecen latencia y otras características, los herpesvirus humanos han sido clasificados en distintas

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Latent herpes simplex virus type 1 in normal and Alzheimer's disease brains

Cited by 267 publications

References 16 publications

Effect of human apolipoprotein E genotype on the pathogenesis of experimental ocular HSV-1

Effect of human apolipoprotein E genotype on the pathogenesis of experimental ocular HSV-1

Autophagy interaction with herpes simplex virus type-1 infection

Herpes simplex virus tipo 1 como factor de riesgo asociado con la enfermedad de Alzheimer

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