HSV-1 Accelerates the Formation of Amyloid Plaques in Mice

Why do only some people suffer Alzheimer's disease? The condition appears to be caused in its earliest stages by progressively increased levels of amyloid-β plaques in the brain, and different people have different degrees of this form of damage. Why does amyloid-β accumulate? It may be due to impaired drainage of cerebrospinal fluid, and thus a failure to clear out this and other forms of metabolic waste. In addition, amyloid-β may play a role in the innate immune response to infection. People with persistent infections such as herpesviruses will tend to generate more amyloid-β over time. As supporting evidence for this latter view of Alzheimer's disease as a consequence of lingering infection, researchers here demonstrate that the herpesvirus HSV-1 is capable of accelerating the formation of amyloid-β plaques in mice.

New research shows that viruses interact with proteins in the biological fluids of their host which results in a layer of proteins on the viral surface. This coat of proteins makes the virus more infectious and facilitates the formation of plaques characteristic of neurodegenerative diseases such as Alzheimer's disease. Before entering a host cell, viruses are just nanometer-sized particles, very similar to artificial nanoparticles used in medical applications for diagnosis and therapy. Scientists have found that viruses and nanoparticles share another important property; they both become covered by a layer of proteins when they encounter the biological fluids of their host before they find their target cell. This layer of proteins on the surface influence their biological activity significantly.

Researchers studied the protein corona of respiratory syncytial virus (RSV) in different biological fluids. The virus remains unchanged on the genetic level, but acquires different identities by accumulating different protein coronae on its surface depending on its environment. This makes it possible for the virus to use extracellular host factors for its benefit, and many of these different coronae make RSV more infectious.

Researchers also found that viruses such as RSV and herpes simplex virus type 1 (HSV-1) can bind a special class of proteins called amyloid proteins. Amyloid proteins aggregate into plaques that play a part in Alzheimer's disease where they lead to neuronal cell death. The mechanism behind the connection between viruses and amyloid plaques has been hard to find till now, but researchers found that HSV-1 is able to accelerate the transformation of soluble amyloid proteins into thread-like structures that constitute the amyloid plaques. In animal models of Alzheimer's disease, they saw that mice developed the disease within 48 hours of infection in the brain. In absence of an HSV-1 infection the process normally takes several months.

Link: https://www.eurekalert.org/pub_releases/2019-05/su-cop052319.php

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