summary: Researchers have identified a new defense mechanism in the brain that prevents the herpes virus from causing severe brain infections, despite the virus being present in more than half of the population.
The findings highlight the protective role of the TMEFF1 gene, which produces a protein that blocks viruses from entering neuronal cells, and may lead to a better understanding of brain immunity and its role in preventing neurodegenerative diseases such as Alzheimer’s.
This study opens up new avenues for studying the brain’s defense mechanisms and their impact on brain health.
Key Facts:
- Spread of infection: More than 50% of people are infected with chronic herpes viruses, but serious brain infections are rare.
- Protective genes: The TMEFF1 gene plays a key role in preventing herpes from invading brain cells.
- Impact on Alzheimer’s: Understanding this defense mechanism may shed light on the relationship between herpes and Alzheimer’s disease.
sauce: Aarhus University
More than half of us are carriers of chronic herpes virus infections.
But while herpes viruses can infect nerve cells, they rarely cause serious infections of the brain, and researchers at Aarhus University have discovered a key element that may explain why.
Researchers have discovered a previously unknown defense mechanism in the body that explains why herpes infections cause severe and potentially fatal encephalitis in just 1 in 250,000 cases. The study was recently published in the scientific journal Nature.
“This study has exciting prospects for improving our understanding of how the brain protects against viral infections,” says Professor Søren Riis Pardun from the Department of Biomedicine at Aarhus University, last author of the paper, Lundbeck Foundation Professor and Director of the Excellence Centre CiViA.
“We discovered how to prevent the herpes virus from invading the brain, even though 50-80% of us are chronically infected with it. The idea behind CiViA is that we want to understand how the body fights infection without harming itself. The mechanism we discovered does not trigger an inflammatory response,” he says.
The answer lies in the protective TMEFF1 gene.
The brain uses a new mechanism to keep viruses at bay
After years of experimentation using genome-wide CRISPR screening techniques and developing mice lacking the key gene, the researchers finally became convinced that TMEFF1 produces a protein that prevents herpes viruses from invading nerve cells.
The study, published in Nature, is accompanied by another paper describing two patients with encephalitis caused by a herpes virus infection, known as herpes encephalitis. In a collaborative study led by researchers in New York, the Aarhus research group discovered that the two children with herpes encephalitis carried a genetic defect that disabled the protective gene TMEFF1.
“This new study is groundbreaking as it updates our fundamental understanding of immunity to viral infections,” explains Soren Riis-Pardhan.
“This is exciting for immunologists because it shows that there are many immunological mechanisms in the brain that we don’t yet know about.
“This work also has important implications for neuroscience because it explains how the brain, so to speak, keeps out intruders without harming the brain itself, the neurons,” he says.
It may help improve our understanding of Alzheimer’s disease
Soren Riis Paludan hopes that this study is the first step in uncovering a whole new range of the brain’s defense mechanisms. One area the researchers are now investigating is what the findings might mean for the development of dementia.
Research has already demonstrated a correlation between infection with the herpes virus and the subsequent development of Alzheimer’s disease.
“Perhaps the discovery of a new antiviral mechanism in the brain will help us to clarify whether individual differences in this particular mechanism or a similar one allow the virus to enter the brain and accelerate the neurodegenerative process,” says Soren Riis-Pardhan.
About this Genetics and Neurology Research News
author: Line Ron
sauce: Aarhus University
contact: Rhine Ron – Oles College
image: Image courtesy of Neuroscience News
Original Research: The access is closed.
“TMEFF1 is a neuron-specific restriction factor for herpes simplex virus” by Søren Riis Paludan et al. Nature
Abstract
TMEFF1 is a neuron-specific restriction factor for herpes simplex virus
The brain is highly sensitive to damage caused by infection and inflammation. Herpes simplex virus type 1 (HSV-1) is a neurotropic virus that causes herpes simplex encephalitis. It is unclear whether neuron-specific antiviral factors regulate viral replication to prevent infection and excessive inflammatory responses, thus protecting the brain.
Here, using a genome-wide CRISPR screen, we identify TMEFF1 as an HSV-1 restriction factor that is specifically expressed in neurons of the central nervous system and is not regulated by type I interferon, the best-known innate antiviral system controlling viral infection.
Depletion of TMEFF1 in stem cell-derived human neurons led to increased viral replication and neuronal death after HSV-1 infection.TMEFF1 inhibited the HSV-1 replication cycle at the level of viral entry through interactions with nectin-1 and nonmuscle myosin heavy chains IIA and IIB, which are core proteins in virus-cell binding and virus-cell fusion, respectively.
especially, Temefu 1−/− Mice were more susceptible to HSV-1 infection in the brain, but not in the periphery, where elevated viral loads were observed specifically in neurons.
Our study identifies TMEFF1 as a neuron-specific restriction factor essential for preventing HSV-1 replication in the central nervous system.
