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| Fused neurons in yellow, expressing Spike S fusogen from the SARS-CoV-2 virus and the human receptor hACE2. Image Credit: Courtesy of University of Queensland |
Scientific Frontline: Extended "At a Glance" Summary: Viral-Induced Neuronal Fusion
The Core Concept: Viral-induced neuronal fusion is a newly identified pathological process where brain cells infected by viruses, such as SARS-CoV-2, merge together rather than undergoing cell death or inflammation. This fusion permanently alters neuronal circuitry, causing the infected neurons to either fire synchronously or cease functioning entirely.
Key Distinction/Mechanism: Previously, viral infection in the brain was understood to result in only two clinical outcomes: cell death or inflammation. The discovery of a third outcome—neuronal fusion mediated by the presence of viral proteins like the spike S protein—highlights a unique mechanism where fused neurons survive but irreversibly lose their independent signaling capabilities.
Origin/History: The mechanism was detailed in a study published in Science Advances in June 2023 by researchers Professor Massimo Hilliard and Dr. Ramon Martinez-Marmol from the Queensland Brain Institute at The University of Queensland, following observations of persistent SARS-CoV-2 in the brains of patients with long COVID.
Major Frameworks/Components:
- Viral protein expression: The presentation of the SARS-CoV-2 spike S protein within neurons directly triggers the cellular fusion event.
- Circuit synchronization: Fused neurons fail to operate as independent circuits, resulting in simultaneous electrical firing or complete functional arrest.
- Broad viral etiology: The mechanism is hypothesized to occur with other neurotropic viruses known to cause fusion in non-neural tissues, including HIV, rabies, Japanese encephalitis, measles, herpes simplex virus, and Zika virus.
Branch of Science: Neuroscience, Virology, and Pathology.
Future Application: Isolating this mechanism provides a novel target for developing therapeutic interventions aimed at preventing cellular fusion in the nervous system, which could treat persistent neurological symptoms associated with long COVID and other neuroinvasive viral infections.
Why It Matters: This discovery offers a critical structural and physiological explanation for the chronic neurological deficits observed in long COVID, establishing a fundamental new framework for investigating unexplored viral-induced neurological diseases.
Professor Massimo Hilliard and Dr Ramon Martinez-Marmol from the Queensland Brain Institute have explored how viruses alter the function of the nervous system.
SARS-CoV-2, the virus that causes COVID-19, has been detected in the brains of people with ‘long COVID’ months after their initial infection.
“We discovered COVID-19 causes neurons to undergo a cell fusion process, which has not been seen before,” Professor Hilliard said.
“After neuronal infection with SARS-CoV-2, the spike S protein becomes present in neurons, and once neurons fuse, they don’t die.”
“They either start firing synchronously, or they stop functioning altogether.”
As an analogy, Professor Hilliard likened the role of neurons to that of wires connecting switches to the lights in a kitchen and a bathroom.
“Once fusion takes place, each switch either turns on both the kitchen and bathroom lights at the same time, or neither of them,” he said.
“It’s bad news for the two independent circuits.”
The discovery offers a potential explanation for persistent neurological effects after a viral infection.
“In the current understanding of what happens when a virus enters the brain, there are two outcomes – either cell death or inflammation,” Dr Martinez-Marmol said.
“But we’ve shown a third possible outcome, which is neuronal fusion.”
Dr Martinez-Marmol said numerous viruses cause cell fusion in other tissues, but also infect the nervous system and could be causing the same problem there.
“These viruses include HIV, rabies, Japanese encephalitis, measles, herpes simplex virus and Zika virus,” he said.
“Our research reveals a new mechanism for the neurological events that happen during a viral infection.
“This is potentially a major cause of neurological diseases and clinical symptoms that is still unexplored.”
Published in journal: Science Advances
Authors: Ramón Martínez-Mármol, Rosina Giordano-Santini, Eva Kaulich, Ann-Na Cho, Magdalena Przybyla, Md Asrafuzzaman Riyadh, Emilija Robinson, Keng Yih Chew, Rumelo Amor, Frédéric A. Meunier, Giuseppe Balistreri, Kirsty R. Short, Yazi D. Ke, Lars M. Ittner, and Massimo A. Hilliard
Source/Credit: University of Queensland
Edited by: Scientific Frontline
Reference Number: vi060823_01
