<i>Herpes simplex</i> virus type 1 DNA is present in specific regions of brain from aged people with and without senile dementia of the Alzheimer type

Jamieson, Gordon A.; Maitland, Norman J.; Wilcock, Gordon; Yates, Celia M.; Itzhaki, Ruth F.

doi:10.1002/path.1711670403

Cited by 135 publications

(85 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Thus, the spinal cord and brain could act as reservoirs of latent virus. Most, if not all, human brains harbor latent viral genomes (14,26,27), but their quiescence or, conversely, their ability to cause harm may depend on their exact location, the immune status of the host, and their copy number (in which ApoE could play an important role). It has been shown that the HSV-1 genome copy number is positively correlated with the ability to reactivate in vivo in neurons of the trigeminal ganglia (46).…”

Section: Discussionmentioning

confidence: 99%

Effect of Apolipoprotein E on the Cerebral Load of Latent Herpes Simplex Virus Type 1 DNA

Burgos

Ramı́rez

Sastre

et al. 2006

J Virol

111

View full text Add to dashboard Cite

Herpes simplex virus type 1 (HSV-1) is neurotropic and enters a latent state lasting the lifetime of the host. This pathogen has recently been proposed as a risk factor for Alzheimer's disease (AD) in conjunction with apolipoprotein E4 (ApoE4). In a murine acute infection model, we showed that viral neuroinvasiveness depends directly on the overall ApoE dosage and especially on the presence of isoform ApoE4. If an interaction between ApoE and HSV-1 is involved in AD, it may occur during latency rather than during acute infection. Certainly, ApoE plays an important role in late-onset AD, i.e., at a time in life when the majority of people harbor HSV-1 in their nervous system. In the present work, wild-type, APOE knockout, APOE3, and APOE4 transgenic mice were used to analyze the influence of the ApoE profile on the levels of latent virus DNA. The knockout mice had significantly lower concentrations of the virus in the nervous system than the wild-type mice, while the APOE4 mice had very high levels in the brain compared to the APOE3 animals. ApoE4 seems to facilitate HSV-1 latency in the brain much more so than ApoE3. The APOE dosage correlated directly with the HSV-1 DNA concentration in the brain, strengthening the hypothesis that HSV-1, together with ApoE, might be involved in AD.

show abstract

Section: Discussionmentioning

confidence: 99%

Effect of Apolipoprotein E on the Cerebral Load of Latent Herpes Simplex Virus Type 1 DNA

Burgos

Ramı́rez

Sastre

et al. 2006

J Virol

111

View full text Add to dashboard Cite

show abstract

“…It is able to perform this task as it possesses an awesome variety of however a plausible role for the HSV-1 viral DNA could be associated with the plaque maturation process. Jamieson et al (127) found that the virus was absent from the brains of most young people, probably because it enters the brain during old age either with immune senescence (130) or the virus itself is initially responsible for weakening the host's immune defenses. This latter explanation is likely and is supported by us and others (131).…”

Section: Possible Consequences To the Brain Carrying Oral Bacterial Pmentioning

confidence: 99%

Inflammasome Involvement in Alzheimer’s Disease

Olsen

Singhrao

2016

JAD

View full text Add to dashboard Cite

Alzheimer's disease (AD) is a scourge of longevity that will drain enormous resources from public health budgets in the future. Currently, there is no diagnostic biomarker and/or treatment for this most common form of dementia in humans. AD can be of early familialonset or sporadic with a late-onset. Apart from the two main hallmarks, amyloid-beta and neurofibrillary tangles, inflammation is a characteristic feature of AD neuropathology.Inflammation may be caused by a local central nervous system insult and/or by peripheral infections. Numerous microorganisms are suspected in AD brains ranging from bacteria (mainly oral and non-oral Treponema species), viruses (Herpes simplex type I) and yeasts (Candida species). A causal relationship between periodontal pathogens/non-oral Treponema species of bacteria has been proposed via the amyloid-beta and inflammatory links.Periodontitis constitutes a peripheral oral infection that can provide the brain with intact bacteria and virulence factors and inflammatory mediators due to daily, transient bacteraemias. If and when genetic risk factors meet environmental risk factors in the brain, disease is expressed, in which neurocognition may be impacted, leading to the development of dementia. To achieve the goal of finding a diagnostic biomarker and possible prophylactic treatment for AD, there is an initial need to solve the etiological puzzle contributing to its pathogenesis. This review therefore addresses oral infection as the plausible aetiology of late onset AD (LOAD). ___________________________________________________________________________Keywords: Alzheimer's disease; pathogenesis; microorganisms; oral bacteria; direct cause 3 Alzheimer's disease (AD) is a neurodegenerative disease and the most common example of a group of diseases that manifest as dementia. It is associated with atrophy and specific neuronal death particularly in the hippocampal region of the brain (1). Research into AD pathogenesis, has flagged two main categories of the disease: the familial onset presentation accounts for around 2% of all AD cases and the sporadic form of late-onset AD also referred to as LOAD constitutes approximately 98% of the cases. LOAD displays genetic susceptibility traits of which the well-known risk factor is inheritance of the apolipoprotein (APOEɛ4) gene allele (2) and, appears to require an environmental factor for disease expression. For example a pathogen-host interaction can exacerbate neurocognition in some elderly individuals who if in their 80+ years likely become diagnosed with LOAD (3, 4). The rationale for this review therefore is to try to explain the aetiology in the vast proportion of LOAD cases that relies upon common risk factors. Several scientists have proposed, one of these to be peripheral infections (5-11), and the accompanying systemic and local inflammatory mediators (11)(12)(13). Of these, the plausible risk from oral infection is the main focus of this review. PREVALENCE OF ADAD is a burden of longevity resulting from the superior qualit...

show abstract

“…[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

View full text Add to dashboard Cite

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.

show abstract

Herpes simplex virus type 1 DNA is present in specific regions of brain from aged people with and without senile dementia of the Alzheimer type

Cited by 135 publications

References 7 publications

Effect of Apolipoprotein E on the Cerebral Load of Latent Herpes Simplex Virus Type 1 DNA

Effect of Apolipoprotein E on the Cerebral Load of Latent Herpes Simplex Virus Type 1 DNA

Inflammasome Involvement in Alzheimer’s Disease

Autophagy interaction with herpes simplex virus type-1 infection

Contact Info

Product

Resources

About