SARS-CoV-2 infection and viral fusogens cause neuronal and glial fusion that compromises neuronal activity, 2023, Hilliard et al

SARS-CoV-2 infection and viral fusogens cause neuronal and glial fusion that compromises neuronal activity
https://www.science.org/doi/10.1126/sciadv.adg2248


Abstract

Numerous viruses use specialized surface molecules called fusogens to enter host cells. Many of these viruses, including the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can infect the brain and are associated with severe neurological symptoms through poorly understood mechanisms.

We show that SARS-CoV-2 infection induces fusion between neurons and between neurons and glia in mouse and human brain organoids. We reveal that this is caused by the viral fusogen, as it is fully mimicked by the expression of the SARS-CoV-2 spike (S) protein or the unrelated fusogen p15 from the baboon orthoreovirus.

We demonstrate that neuronal fusion is a progressive event, leads to the formation of multicellular syncytia, and causes the spread of large molecules and organelles.

Last, using Ca2+ imaging, we show that fusion severely compromises neuronal activity. These results provide mechanistic insights into how SARS-CoV-2 and other viruses affect the nervous system, alter its function, and cause neuropathology.


Edit: in mice

 

Article with summary of research: https://medicalxpress.com/news/2023-06-covid-brain-cells-fuse.html.

"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."
...
"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."
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I posted this in the COVID general forum, but the researchers seem to think that this is relevant to LC. However the study was in mice, so long way to go.

Video interview:

https://twitter.com/user/status/1666724459913543681

 

Since we've never observed this before, it's a big discovery. Now we need to see if other viruses cause it, if it happens in humans, and what effects it has.

 

The study mentioned about 8 viruses by name that they either suspect or have observed this in, including the usual suspects for ME/CFS. Have only read a news summary of the article, but will be reading the entire thing tomorrow and can summarize for spoonies if someone else hasn't already done it. (Am healthy caregiver.)

 

Still working my way through the paper, folks, and egads, they found the fusion happened in *human embryonic stem-cell-derived neural organoids* after exposing to the SARS-Cov2 virus. Not just in the meecies! This looks like a smoking gun.