In the past four years, the pathogen responsible for Coronavirus Disease 2019 (COVID-19), SARS-CoV-2, has infected more than 770 million people and caused more than 6.9 million deaths worldwide. The severe impact of SARS-CoV-2 is often attributed to its ability to suppress the interferon (IFN) response while simultaneously inducing the production of various cytokines.
To address this question, a research team led by Prof. Xue Yuanchao from the Institute of Biophysics of the Chinese Academy of Sciences, together with their collaborators, has profiled the SARS-CoV-2-to-host RNA–RNA interactions.
This study, published in Molecular Cell on Dec. 20, unveils for the first time the molecular intricacies of how SARS-CoV-2 RNA interacts with and stabilizes host mRNAs, ultimately triggering the cytokine storm.
Using state-of-the-art RIC-seq technology, the researchers comprehensively mapped the SARS-CoV-2-to-host RNA–RNA interactions in infected cells and lung tissues obtained from two deceased COVID-19 patients. Through mass spectrometry analysis of the RNA pull-down assay, they discovered that SARS-CoV-2 RNA forms base pairs with the 3′ UTR of host mRNAs and recruits the RNA-binding protein YBX3 to stabilize host mRNAs in A549-ACE2 and Vero cells. Importantly, interference with the SARS-CoV-2-to-host RNA–RNA interaction or the knockdown of YBX3 significantly reduced host mRNA stability and hindered SARS-CoV-2 replication.
Among the stabilized host mRNAs, NFKBIZ emerged as a key factor in promoting cytokine production and suppressing IFN responses, potentially contributing to the cytokine storm. Knocking down NFKBIZ resulted in a significant decrease in the expression levels of proinflammatory factors such as IL-6, IL-8, and CXCL2, while the levels of type I/III IFNs, including IFNB1, IFNL1, and IFNL2, increased. These findings suggest that SARS-CoV-2 may induce a cytokine storm via stabilized host mRNAs, with NFKBIZ playing a pivotal role.
This research not only sheds light on the regulatory role of RNA–RNA interactions in the immunopathogenesis of RNA viruses such as SARS-CoV-2, but also contributes to the development of novel strategies to combat COVID-19.
The results open new avenues for targeted interventions aimed at disrupting the specific molecular mechanisms responsible for the cytokine storm associated with severe cases of COVID-19.
More information: Hailian Zhao et al, SARS-CoV-2 RNA stabilizes host mRNAs to elicit immunopathogenesis, Molecular Cell (2023). DOI: 10.1016/j.molcel.2023.11.032
News
New Drug Kills Cancer 20,000x More Effectively With No Detectable Side Effects
By restructuring a common chemotherapy drug, scientists increased its potency by 20,000 times. In a significant step forward for cancer therapy, researchers at Northwestern University have redesigned the molecular structure of a well-known chemotherapy drug, greatly [...]
Lipid nanoparticles discovered that can deliver mRNA directly into heart muscle cells
Cardiovascular disease continues to be the leading cause of death worldwide. But advances in heart-failure therapeutics have stalled, largely due to the difficulty of delivering treatments at the cellular level. Now, a UC Berkeley-led [...]
The basic mechanisms of visual attention emerged over 500 million years ago, study suggests
The brain does not need its sophisticated cortex to interpret the visual world. A new study published in PLOS Biology demonstrates that a much older structure, the superior colliculus, contains the necessary circuitry to perform the [...]
AI Is Overheating. This New Technology Could Be the Fix
Engineers have developed a passive evaporative cooling membrane that dramatically improves heat removal for electronics and data centers Engineers at the University of California San Diego have created an innovative cooling system designed to greatly enhance [...]
New nanomedicine wipes out leukemia in animal study
In a promising advance for cancer treatment, Northwestern University scientists have re-engineered the molecular structure of a common chemotherapy drug, making it dramatically more soluble and effective and less toxic. In the new study, [...]
Mystery Solved: Scientists Find Cause for Unexplained, Deadly Diseases
A study reveals that a protein called RPA is essential for maintaining chromosome stability by stimulating telomerase. New findings from the University of Wisconsin-Madison suggest that problems with a key protein that helps preserve chromosome stability [...]
Nanotech Blocks Infection and Speed Up Chronic Wound Recovery
A new nanotech-based formulation using quercetin and omega-3 fatty acids shows promise in halting bacterial biofilms and boosting skin cell repair. Scientists have developed a nanotechnology-based treatment to fight bacterial biofilms in wound infections. The [...]
Researchers propose five key questions for effective adoption of AI in clinical practice
While Artificial Intelligence (AI) can be a powerful tool that physicians can use to help diagnose their patients and has great potential to improve accuracy, efficiency and patient safety, it has its drawbacks. It [...]
Advancements and clinical translation of intelligent nanodrugs for breast cancer treatment
A comprehensive review in "Biofunct. Mater." meticulously details the most recent advancements and clinical translation of intelligent nanodrugs for breast cancer treatment. This paper presents an exhaustive overview of subtype-specific nanostrategies, the clinical benefits [...]
It’s Not “All in Your Head”: Scientists Develop Revolutionary Blood Test for Chronic Fatigue Syndrome
A 96% accurate blood test for ME/CFS could transform diagnosis and pave the way for future long COVID detection. Researchers from the University of East Anglia and Oxford Biodynamics have created a highly accurate [...]
How Far Can the Body Go? Scientists Find the Ultimate Limit of Human Endurance
Even the most elite endurance athletes can’t outrun biology. A new study finds that humans hit a metabolic ceiling at about 2.5 times their resting energy burn. When ultra-runners take on races that last [...]
World’s Rivers “Overdosing” on Human Antibiotics, Study Finds
Researchers estimate that approximately 8,500 tons of antibiotics enter river systems each year after passing through the human body and wastewater treatment processes. Rivers spanning millions of kilometers across the globe are contaminated with [...]
Yale Scientists Solve a Century-Old Brain Wave Mystery
Yale scientists traced gamma brain waves to thalamus-cortex interactions. The discovery could reveal how brain rhythms shape perception and disease. For more than a century, scientists have observed rhythmic waves of synchronized neuronal activity [...]
Can introducing peanuts early prevent allergies? Real-world data confirms it helps
New evidence from a large U.S. primary care network shows that early peanut introduction, endorsed in 2015 and 2017 guidelines, was followed by a marked decline in clinician-diagnosed peanut and overall food allergies among [...]
Nanoparticle blueprints reveal path to smarter medicines
Lipid nanoparticles (LNPs) are the delivery vehicles of modern medicine, carrying cancer drugs, gene therapies and vaccines into cells. Until recently, many scientists assumed that all LNPs followed more or less the same blueprint, [...]
How nanomedicine and AI are teaming up to tackle neurodegenerative diseases
When I first realized the scale of the challenge posed by neurodegenerative diseases, such as Alzheimer's, Parkinson's disease and amyotrophic lateral sclerosis (ALS), I felt simultaneously humbled and motivated. These disorders are not caused [...]
