Genetic Variant Tunes Immune Response and Disease Susceptibility
Ancient ‘Bug’ in Our DNA May Hold Key to Understanding COVID Severity
New research suggests a genetic quirk, originating millions of years ago, could explain why some people experience severe COVID-19 while others have mild cases.
Scientists have long been puzzled by the wide range of COVID-19 symptoms, from asymptomatic infection to life-threatening illness.A new study from the University of Colorado Boulder points to a surprising culprit: an ancient genetic “bug” that may be acting as an immune system “tuning dial.”
the study, published in the journal Cell, focuses on a protein called IFNAR2, which plays a crucial role in our immune response to viruses.Researchers discovered a variant of this protein, created by a piece of “junk DNA” called a transposon, that acts like a decoy, interfering with the normal immune response.
“We’ve discovered that there is an entire class of under-appreciated protein variants that can have an immense impact on our immune function,” said Ed Chuong, lead author of the study and assistant professor in the Department of Molecular, Cellular and Developmental Biology.
From ‘Junk DNA’ to Immune Regulator
Transposons, frequently enough referred to as “jumping genes,” are remnants of ancient viral infections that have become embedded in our DNA. For decades, scientists considered them inert, but Chuong’s team suspected they might play a role in immune function.
Their analysis of genetic data revealed a variant of IFNAR2 created by a transposon. This variant,while able to sense viral signals,lacked the ability to transmit them effectively,essentially acting as a “brake” on the immune response.Laboratory experiments confirmed this finding. Cells with higher levels of the variant showed weaker immune responses to viruses, including SARS-CoV-2 and dengue virus.
Implications for COVID-19 and Beyond
The discovery suggests that the balance between the normal IFNAR2 protein and its variant acts as a “tuning dial” for the immune system. Individuals with a higher proportion of the variant may be more susceptible to severe COVID-19, while those with lower levels might experience milder symptoms.
This finding could have far-reaching implications, not just for COVID-19 but also for other infectious diseases, autoimmune disorders, and even cancer.
“If we can manipulate this dial to turn the immune system up or down it could have broad therapeutic applications,” said Chuong.
The team is now working on developing therapies that target this “tuning dial,” potentially paving the way for personalized treatments based on an individual’s genetic makeup.
This groundbreaking research highlights the importance of exploring the often-overlooked regions of our genome. As chuong notes, “Our findings suggest that looking into the dark corners of the genome is key to making new discoveries to improve human health.”
Ancient Genetic Glitch May Hold Key to Understanding COVID Severity
NewsDirectory3: Could a millennia-old genetic quirk be the reason why some people experience mild COVID-19 while others face severe illness? New research from the University of Colorado Boulder suggests that an ancient genetic “bug” might potentially be acting like an immune system “tuning dial,” potentially explaining the wide range of COVID-19 symptom severity.
Published in the journal Cell, the study focuses on a protein called IFNAR2, crucial for our immune response to viruses. Researchers discovered a variant of this protein, created by a piece of “junk DNA” called a transposon, that interferes with the normal immune response.
“We’ve discovered that ther is an entire class of under-appreciated protein variants that can have an immense impact on our immune function,” said Ed Chuong, lead author of the study and assistant professor in the Department of Molecular, Cellular and Developmental Biology.
This variant, while able to sense viral signals, lacks the ability to effectively transmit them, essentially acting as a “brake” on the immune response. Experiments confirmed that cells with higher levels of this variant showed weaker immune responses to viruses, including SARS-CoV-2 and dengue virus.
The discovery suggests the balance between the normal IFNAR2 protein and its variant acts as a ”tuning dial” for the immune system. Individuals with a higher proportion of the variant might potentially be more susceptible to severe COVID-19, while those with lower levels might experience milder symptoms.
This finding could have far-reaching implications for treating not only COVID-19 but also other infectious diseases, autoimmune disorders, and even cancer.
“If we can manipulate this dial to turn the immune system up or down, it could have broad therapeutic applications,” said Chuong.
The team is now developing therapies that target this “tuning dial,” potentially paving the way for personalized treatments based on an individual’s genetic makeup.
This research highlights the importance of exploring the frequently enough-overlooked regions of our genome, as “looking into the dark corners of the genome is key to making new discoveries to improve human health,” Chuong emphasizes.