Subacute sclerosing panencephalitis is a rare complication with debilitating effects: it causes mental deterioration, massive bilateral myoclonus and seizures. Although the normal form of the measles virus cannot infect the nervous system, the team shows that viruses that persist in the body can develop mutations in a key protein that controls how they infect cells. The mutated proteins can interact with its normal form, which then makes it capable of infecting the brain.
A mutant virus capable of infecting the brain
Many people born following the 1970s have never contracted the measles virus, thanks to vaccination. Nevertheless, the virus remains one of the most contagious pathogens to date. Its R0 or reproduction number per case has been estimated at 18. The World Health Organization (WHO) estimates that nearly 9 million people worldwide were infected with measles in 2021, with this incidence resulting in 128,000 death.
“The disease therefore remains a concern, especially as the COVID-19 pandemic has reduced vaccination, particularly in southern countries”explains Yuta Shirogane, professor at Kyushu University: “Subacute sclerosing panencephalitis is a rare but fatal complication yet the normal measles virus does not have the ability to spread in the brain, and it is still unknown today how it causes encephalitis.”
RNA viruses like the measles virus mutate and evolve at very high rates,
but the evolutionary mechanism allowing the virus to infect neurons remained misunderstood.
The brain infection process deciphered: a virus typically infects cells through a series of proteins that protrude from its surface. Usually, one protein first facilitates attachment of the virus to the surface of the host cell, then another surface protein causes a reaction that allows the virus to enter the cell, resulting in infection. Thus, the type of cell also “counts” in the infectious capacity of the virus.
- Usually, the measles virus only infects immune and epithelial cells. But in the case of subacute sclerosing panencephalitis, the virus stays in the body for a while and mutates so that it acquires the ability to infect nerve cells.
The key role of a fusion protein: this F protein is identified as a key player that allows the measles virus to infect a brain cell. So research shows that:
- certain mutations of the F protein place it in a state allowing it to “fuse” with neural synapses and infect the brain. The demonstration here involves the analysis of the genome of measles virus from patients with subacute sclerosing panencephalitis, which reveals different mutations in the F protein.
- Interestingly, some mutations seem to “boost” the infection.
- Specifically, when the virus infects a neuron, it infects it by a mechanism of “en bloc transmission”, by which several copies of the viral genome enter the cell simultaneously. The genome encoding the mutant F protein is transmitted simultaneously with the genome of the normal F protein and the two proteins coexist in the infected cell.
Analysis of the fusion activity of mutant F proteins, when normal F proteins are also present, reveals that if the fusion activity of a mutant F protein would normally be suppressed due to interference from F proteins normal, cThis interference is overcome by the accumulation of mutations in the F protein.
This work, which thus deciphers the mechanism of infection of the brain by the measles virus, also suggests a possible target, the mutated F protein, to prevent this type of severe neurological complication, in particular in unvaccinated adults.