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How measles viruses infect brain cells

Damage to the brain, usually fatal, is the dreaded long-term consequence of a measles infection.

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How measles viruses infect brain cells

Damage to the brain, usually fatal, is the dreaded long-term consequence of a measles infection. In order to trigger what is known as subacute sclerosing panencephalitis (SSPE), the pathogens have to penetrate the brain. Japanese scientists have found out under what circumstances they succeed. According to this, measles viruses with different gene variants together manage to infect nerve cells in the brain.

The wild-type virus is not able to do this, nor are individual virus types with certain mutations. But when they interact, they can spread in the brain and trigger the usually deadly brain disease, as the group led by Yuta Shirogane from Kyushu University in Fukuoka reports in the journal Science Advances.

SSPE is extremely rare in the US and Western Europe because of widespread measles vaccination. However, tragically, infants who have not yet been vaccinated are often infected - for example, if an unvaccinated person with measles was in a practice at the same time or hours before. The risk of developing SSPE is highest in people who developed measles before the age of two.

The neurodegenerative disease mostly occurs several years after an acute measles infection. "Usually, the measles virus only infects immune and epithelial cells, causing fever and rash," Shirogane explained. In order to be able to penetrate nerve cells, the virus must mutate. Central to this are mutations in the so-called F-protein, which causes the virus envelope and the outer membrane of a body cell to fuse (fuse, hence “F-protein”).

The study authors used data on gene mutations in the measles viruses of SSPE patients. They found various mutations, the effects of which they tested in experiments on the brains of mouse embryos. They found that a specific mutation of the F protein does not allow the virus to penetrate brain cells. "It was surprising to see," says Shirogane. After all, how can a mutation lead to a brain infection if it does not allow the main obstacle, penetration into nerve cells?

But the researchers found an explanation, namely a so-called en bloc transmission. The F protein can not only bring about a fusion of the viral envelope and cell membrane, but also the fusion of an infected cell with an uninfected cell. In nerve cells, this happens at the synapses between the extension (axon) of one nerve cell and another. During this fusion, the synaptic gap is bridged and the virus can reach the next nerve cell unhindered. Different genetic variants of the virus are often present together in one cell and are passed on together ("en bloc").

Shirogane and colleagues have now found that the seemingly pointless F protein mutation allows the virus to enter nerve cells when the wild-type F protein is present at the same time. In most other mutations of the F protein, on the other hand, the wild type caused little or no penetration into nerve cells. The different mutations can thus interfere with each other in the success of the infection or make it possible in the first place. This phenomenon, which was only discovered a few years ago, is called "sociovirology" - the different virus variants influence each other like a social group.

The researchers put the incidence of SSPE at four to eleven per 100,000 cases of measles. Because of the global measles vaccinations, the absolute number of SSPE cases has fallen sharply in recent decades. However, scientists worry that the number could rise again. The corona pandemic has set back vaccination programs, especially in the Global South, Shirogane said. Funds earmarked for vaccinations against measles were often used for vaccinations against SARS-Cov-2. Shirogane hopes the knowledge gained will lead to medical interventions to combat SSPE.

So far the disease cannot be stopped. Early signs such as forgetfulness and irritability are followed by symptoms such as hallucinations and seizures. Mental decline, speech disorders, muscle stiffness and swallowing problems follow. Death usually occurs one to three years after the onset.

"Aha! Ten minutes of everyday knowledge" is WELT's knowledge podcast. Every Tuesday and Thursday we answer everyday questions from the field of science. Subscribe to the podcast on Spotify, Apple Podcasts, Deezer, Amazon Music, among others, or directly via RSS feed.

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