Chickenpox virus causes the onset of Alzheimer’s disease

Summary: Varicella zoster virus (VZV), the virus that causes chickenpox and shingles, activates herpes simplex virus and triggers the onset of Alzheimer’s disease, a new study in mice shows.

A source: Tufts University

Alzheimer’s disease can begin almost unnoticed, often masquerading as forgetfulness, which is common in the early months or young adults. What caused the disease remains a mystery.

But using a three-dimensional model of human tissue that mimics the brain, researchers at Tufts University and Oxford University have shown that the varicella zoster virus (VZV), which commonly causes chickenpox and shingles, can activate another common herpes simplex virus (HSV). virus to trigger the early stages of Alzheimer’s disease.

Normally HSV-1 – one of the main variants of the virus – lies dormant inside the neurons of the brain, but when it is activated it causes the accumulation of tau and amyloid beta proteins and loss of neuronal function – the signature symptoms found in patients. With Alzheimer’s disease.

“Our findings suggest a pathway to Alzheimer’s disease caused by VZV infection, which creates HSV-induced inflammatory triggers in the brain,” said Dana Cairns, GBS12, research fellow in the Department of Biomedical Engineering. “Although we have shown a link between VZV and HSV-1 activation, other inflammatory events in the brain may also activate HSV-1 and lead to Alzheimer’s disease.”

The study was published Journal of Alzheimer’s Disease

Viruses are waiting

“We’re working with a lot of evidence for an increased risk of Alzheimer’s disease in HSV patients,” said David Kaplan, Stern Professor of Family Engineering and head of biomedical engineering at Tufts School of Engineering. One of the first to hypothesize a link between the herpes virus and Alzheimer’s disease is Ruth Itzhaky of the University of Oxford, who collaborated with Kaplan’s lab on this study.

“We know there is a correlation between HSV-1 and Alzheimer’s disease, and some have suggested the involvement of VZV, but we didn’t know the sequence of events that the viruses set off to trigger the disease,” he said. “We now think we have evidence of those events.”

According to the World Health Organization, approximately 3.7 billion people under the age of 50 are infected with HSV-1, the virus that causes oral herpes. In most cases, it is asymptomatic, lying dormant inside nerve cells.

When applied, it causes inflammation in the nerves and skin, causing painful open sores and blisters. Most carriers — about one in two Americans, according to the CDC — have very mild or no symptoms until the virus goes dormant.

Varicella zoster virus is also very common, with about 95 percent of people infected by the age of 20. Most of them are chicken pox. VZV, a type of herpes virus, can also remain in the body, find its way into nerve cells, and become dormant.

Later in life, VZV can reactivate to form tumors, a disease characterized by blisters and nodules on the skin that form a band-like pattern and can be very painful and last for weeks or even months. Every third person will suffer from cancer during their lifetime.

The link between HSV-1 and Alzheimer’s disease only occurs when HSV-1 is reactivated to cause sores, blisters, and other painful inflammatory conditions.

How dormant viruses can be awakened

To better understand the cause-and-effect relationship between viruses and Alzheimer’s disease, Tufts researchers recreated brain-like environments in tiny 6-millimeter-wide donut-shaped sponges made of silk protein and collagen.

They infused the sponges with neural stem cells, which grew into functional neurons capable of transmitting signals to each other in a network similar to the brain. Some stem cells make glial cells, which are normally found in the brain and help keep neurons alive and functioning.

The researchers found that neurons growing in brain tissue could be infected with VZV, but that alone did not cause the Alzheimer’s proteins tau and beta-amyloids — components of the tangled mess of fibers and plaques that form in Alzheimer’s — to form. The patients’ brains and neurons continued to function normally.

Varicella zoster virus (VZV), which commonly causes chicken pox and edema, activates herpes simplex virus (HSV) from dormancy in neural tissue grown in vitro, which then become symptoms of Alzheimer’s disease. Credit: Tufts University

However, if HSV-1 is persistent in neurons, exposure to VZV leads to HSV reactivation, leading to dramatic increases in tau and beta-amyloid proteins, and neuronal signaling begins to slow down.

“It’s a one-two punch, they’re very common and usually harmless, but lab tests show they can cause problems if new exposure to VZV awakens dormant HSV-1,” Cairns said.

“Other infections and other causative pathways can lead to Alzheimer’s disease, and risk factors such as head trauma, obesity or alcohol consumption can be cut off when HSV re-emerges in the brain,” he said. has joined.

The researchers found that samples infected with VZV produced high levels of cytokines, proteins that often trigger an inflammatory response. Kaplan notes that VZV causes inflammation in the brain in many clinical cases, possibly leading to activation of dormant HSV and increased inflammation.

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Repeated cycles of HSV-1 activation can lead to more inflammation in the brain, plaque formation, and accumulation of neuronal and cognitive damage.

The VZV vaccine is effective in preventing chicken pox and measles, as well as significantly reducing the risk of dementia. This vaccine may help stop the cycle of viral reactivation, inflammation, and neuronal damage.

The researchers also noted the long-term neurological effects that some COVID patients experience from SARS-CoV-2, especially in the elderly, and that both VZV and HSV-1 can be reactivated after COVID infection. In such cases, it would be worthwhile to look for later cognitive effects and neurodegeneration, they said.

This is Alzheimer’s disease and virology research news

Author: Mike Silver
A source: Tufts University
The connection: Mike Silver – Tufts University
Photo: Photo courtesy of Tufts University

Original research: Closed access.
Dana Cairns et al. Journal of Alzheimer’s Disease


Abstract

Potential Involvement of Varicella Zoster Virus in Alzheimer’s Disease by Reactivation of Dormant Herpes Simplex Virus Type 1

Background: Varicella zoster virus (VZV) has been implicated in Alzheimer’s disease (AD), and vaccination against VZV-induced varicella has been shown to reduce the risk of AD/dementia. VZV can remain latent in the brain, and reactivation can cause direct damage in AD, as suggested for herpes simplex virus type 1 (HSV-1), which is strongly associated with AD. Alternatively, the tumor may induce neuroinflammation and subsequent reactivation of HSV-1 in the brain.

Purpose: To investigate these possibilities by comparing the effects of VZV and HSV-1 infection on cultured cells and the effects of VZV infection on cells quiescently infected with HSV-1. Methods: We infected human induced neuronal cell (hiNSC) cultures with HSV-1 and/or VZV and looked for AD-related phenotypes such as amyloid-β (Aβ) and P-tau accumulation, gliosis, and neuroinflammation.

Results: VZV-infected cells did not show the core AD hallmarks, Aβ and P-tau accumulation, that HSV-1 causes, but did show gliosis and increased levels of pro-inflammatory cytokines, suggesting that the action of VZV in AD/dementia is indirect. . Interestingly, we found that VZV infection of HSV-1-quiescent cells induces HSV-1 reactivation and consequent AD-like changes, including Aβ and P-tau accumulation.

A result: Our results are consistent with the suggestion that blackmail mediates the reactivation of HSV1 in the brain and the protective effects of various vaccines against AD, as well as the reduction of herpes labialis after certain types of vaccination. They support an indirect role for VZV in AD/dementia through reactivation of HSV-1 in the brain.

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