COVID-19 can cause brain cell fusion and impair neuron activity and brain function

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COVID-19 can cause brain cell fusion and impair neuron activity and brain function

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COVID-19 can cause brain cell fusion and impair neuron activity and brain function. COVID-19 can cause brain cell fusion, which in turn impairs neuron activity and brain function. 

Infectious diseases involving the nervous system are caused by a variety of factors, including bacteria, fungi, parasites and viruses. Rabies virus, herpes simplex virus, Epstein-Barr virus, Zika virus, reovirus, and SARS-CoV-2 are all capable of infecting neurons. Viral brain infections are characterized by a variety of neurologic symptoms, including headache, fever, confusion, seizures, and loss of taste or smell.

In more severe cases, viral brain infections can lead to encephalitis, meningitis, and potentially irreversible neuronal deficits such as paralysis and death.

These clinical symptoms can result from the death of infected neurons; however, some viral infections do not kill host cells, and the chronic neurologic sequelae of these infections cannot be explained by neuronal death.

Therefore, there may be other mechanisms of neuropathology following viral infection of the brain, leading to brain dysfunction.

On June 7, 2023, researchers from the University of Queensland published a research paper titled: SARS-CoV-2 infection and viral fusogens cause neuronal and glial fusion that compromises neuronal activity in Science Advances, a sub-journal of Science [1] .

This study found for the first time that after the new coronavirus infected the brain, it would lead to cell fusion between neurons and between neurons and glia, which would cause abnormal neuronal activity and lead to chronic neurological symptoms .

These findings provide new mechanistic insights into how 2019-nCoV and other viruses affect the nervous system, alter its function and lead to neuropathology, and also provide a potential explanation for the persistent effects on the nervous system after 2019-nCoV infection (long-term COVID-19) .

In non-neuronal tissues, enveloped and reoviruses fuse with host cell membranes and enter cells by using specialized molecules called fusogens .

These viruses then hijack the cellular machinery to produce viral components, and newly synthesized viral fusogens remodel the cell membrane and give it the ability to fuse with neighboring cells.

This leads to the formation of multinucleated syncytia, allowing the virus to spread “from the inside” without the release of virus particles into the extracellular space.

In fact, as early as April 2021, the team of Researcher Sun Qiang of the Academy of Military Medical Sciences, Professor Huang Hongyan of Capital Medical University , and Professor Liu Liang of Tongji Medical College of Huazhong University of Science and Technology had published a research paper in the journal Cell Death & Differentiation [2] .

For the first time, the heterogeneous cell-in-cell structure formed by multinucleated syncytia and lymphocytes is commonly found in the lung tissue of patients with COVID-19 virus, and it is proved that this unique structure is mediated by the spike protein (S protein) during the infection of the COVID-19n virus. Epithelial cells fuse and internalize to form lymphocytes.

For the nervous system, the nervous system is composed of discrete neurons that function as individual units, and their development and communication of information is not based on fusion between cells, but through the transmission of biological, chemical and electrical signals.

The individual independence of neurons is essential for the proper function of the nervous system, but whether viral infection and the resulting viral fusogens lead to neuronal fusion and the formation of multinucleated syncytia, permanently altering neural circuits and function, is currently unknown. Not sure.

In this latest study, researchers from UQ’s Queensland Brain Institute explored how viruses alter nervous system function.

They found that the presence of the new coronavirus could be detected in the brains of long-term COVID-19 patients months after infection. These new coronaviruses cause brain neurons to undergo a cell fusion process that has never been seen before.

After the neurons are infected by the new coronavirus, the spike protein (S protein) of the new coronavirus will appear on the neurons. Once the neurons fuse , Instead of dying, they either start discharging in sync or stop working altogether.

Specifically, the research team found that SARS-CoV-2 infection induced fusion between neurons and between neurons and glia in mouse and human brain organoids. This fusion is mediated by the viral fusogen and can be fully reproduced by the expression of the 2019-nCoV spike protein (S protein) or the unrelated fusogen p15 from the baboon orthoreovirus .

SARS-CoV-2 infection induces neuronal fusion

The research team also demonstrated that this viral infection-induced neuronal fusion is a gradual event that leads to the formation of multicellular syncytia and the diffusion of macromolecules and organelles within them.

Finally, the research team used Ca2+ imaging and found that these neuronal fusions severely impaired neuronal activity. These findings provide new mechanistic insights into how SARS-CoV-2 and other viruses affect the nervous system, altering its function and causing neuropathology.

Neuronal fusion results in altered synaptic activity

The research team likened the neurons to the wires connecting the light switches in the kitchen and bathroom. Once they fuse, the switch will either turn on both kitchen and bathroom lights, or neither will turn on, which is obviously bad news.

This finding also provides a potential explanation for the persistent effects of the new coronavirus on the nervous system after infection.

While virus infection of brain cells was previously known to have two outcomes— cell death or inflammation —this latest research suggests a third possible outcome— neuron fusion .

Many viral infections cause cell fusion in other tissues, and they can cause the same problems in the nervous system after they infect them.

According to the research team, this study reveals a new mechanism of neural events that occur during viral infection, which may be a new and important cause of neurological diseases and clinical symptoms that have not been discovered before.

HIV, rabies virus, Japanese encephalitis virus, measles virus, herpes simplex virus, and Zika virus can all infect brain cells. The impact of these viral infections on the brain also deserves our attention.

Paper link :
https://www.science.org/doi/10.1126/sciadv.adg2248

COVID-19 can cause brain cell fusion and impair neuron activity and brain function

(source:internet, reference only)

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