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
Studies detail high rates of long COVID among healthcare, dental workers
Researchers have estimated approximately 8% of Americas have ever experienced long COVID, or lasting symptoms, following an acute COVID-19 infection. Now two recent international studies suggest that the percentage is much higher among healthcare workers [...]
Melting Arctic Ice May Unleash Ancient Deadly Diseases, Scientists Warn
Melting Arctic ice increases human and animal interactions, raising the risk of infectious disease spread. Researchers urge early intervention and surveillance. Climate change is opening new pathways for the spread of infectious diseases such [...]
Scientists May Have Found a Secret Weapon To Stop Pancreatic Cancer Before It Starts
Researchers at Cold Spring Harbor Laboratory have found that blocking the FGFR2 and EGFR genes can stop early-stage pancreatic cancer from progressing, offering a promising path toward prevention. Pancreatic cancer is expected to become [...]
Breakthrough Drug Restores Vision: Researchers Successfully Reverse Retinal Damage
Blocking the PROX1 protein allowed KAIST researchers to regenerate damaged retinas and restore vision in mice. Vision is one of the most important human senses, yet more than 300 million people around the world are at [...]
Differentiating cancerous and healthy cells through motion analysis
Researchers from Tokyo Metropolitan University have found that the motion of unlabeled cells can be used to tell whether they are cancerous or healthy. They observed malignant fibrosarcoma cells and [...]
This Tiny Cellular Gate Could Be the Key to Curing Cancer – And Regrowing Hair
After more than five decades of mystery, scientists have finally unveiled the detailed structure and function of a long-theorized molecular machine in our mitochondria — the mitochondrial pyruvate carrier. This microscopic gatekeeper controls how [...]
Unlocking Vision’s Secrets: Researchers Reveal 3D Structure of Key Eye Protein
Researchers have uncovered the 3D structure of RBP3, a key protein in vision, revealing how it transports retinoids and fatty acids and how its dysfunction may lead to retinal diseases. Proteins play a critical [...]
5 Key Facts About Nanoplastics and How They Affect the Human Body
Nanoplastics are typically defined as plastic particles smaller than 1000 nanometers. These particles are increasingly being detected in human tissues: they can bypass biological barriers, accumulate in organs, and may influence health in ways [...]
Measles Is Back: Doctors Warn of Dangerous Surge Across the U.S.
Parents are encouraged to contact their pediatrician if their child has been exposed to measles or is showing symptoms. Pediatric infectious disease experts are emphasizing the critical importance of measles vaccination, as the highly [...]
AI at the Speed of Light: How Silicon Photonics Are Reinventing Hardware
A cutting-edge AI acceleration platform powered by light rather than electricity could revolutionize how AI is trained and deployed. Using photonic integrated circuits made from advanced III-V semiconductors, researchers have developed a system that vastly [...]
A Grain of Brain, 523 Million Synapses, Most Complicated Neuroscience Experiment Ever Attempted
A team of over 150 scientists has achieved what once seemed impossible: a complete wiring and activity map of a tiny section of a mammalian brain. This feat, part of the MICrONS Project, rivals [...]
The Secret “Radar” Bacteria Use To Outsmart Their Enemies
A chemical radar allows bacteria to sense and eliminate predators. Investigating how microorganisms communicate deepens our understanding of the complex ecological interactions that shape our environment is an area of key focus for the [...]
Psychologists explore ethical issues associated with human-AI relationships
It's becoming increasingly commonplace for people to develop intimate, long-term relationships with artificial intelligence (AI) technologies. At their extreme, people have "married" their AI companions in non-legally binding ceremonies, and at least two people [...]
When You Lose Weight, Where Does It Actually Go?
Most health professionals lack a clear understanding of how body fat is lost, often subscribing to misconceptions like fat converting to energy or muscle. The truth is, fat is actually broken down into carbon [...]
How Everyday Plastics Quietly Turn Into DNA-Damaging Nanoparticles
The same unique structure that makes plastic so versatile also makes it susceptible to breaking down into harmful micro- and nanoscale particles. The world is saturated with trillions of microscopic and nanoscopic plastic particles, some smaller [...]
AI Outperforms Physicians in Real-World Urgent Care Decisions, Study Finds
The study, conducted at the virtual urgent care clinic Cedars-Sinai Connect in LA, compared recommendations given in about 500 visits of adult patients with relatively common symptoms – respiratory, urinary, eye, vaginal and dental. [...]
