Measles infections have a dreaded long-term consequence: the so-called subacute sclerosing panencephalitis (SSPE), a mostly fatal brain damage. In order to trigger such, the pathogens must penetrate into the brain. And they obviously cannot do this alone: the wild type of the virus is not able to do this, nor are individual virus types with certain mutations. Together, however, viruses with different gene variants become dangerous: As Japanese scientists led by Yuta Shirogane from Kyushu University in Fukuoka wrote in the journal Science Advances reports, the viruses can spread in interaction in the brain and trigger the mostly fatal disease.
SSPE is extremely rare in the US and western Europe because of widespread measles vaccination. However, 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 usually occurs several years after an acute measles infection. 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.
“Usually, the measles virus infects only immune and epithelial cells, causing fever and rash,” Yuta 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 with one another. The name “F protein” indicates this fusion.
Researchers speak of “sociovirology”: virus variants influence each other
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 discovered that a specific mutation of the F protein does not in itself allow the virus to penetrate brain cells. This was only possible through 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 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 neurons 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 worldwide 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. Money earmarked for vaccinations against measles was often used for vaccinations against Sars-Cov-2.