Measles: Japanese researchers uncover mechanism that causes SSPE
by NewsDesk Lord, save her
Researchers in Japan have revealed the mechanism of how the measles virus can cause subacute sclerosing panencephalitis, or SSPE, a rare but fatal neurological disorder that can develop several years after infection with measles.
Although the normal form of the measles virus cannot infect the nervous system, the team found that viruses that persist in the body can develop mutations in a key protein that controls how cells are infected. The transgenic proteins can interact with their normal form, making them capable of infecting the brain. Their findings have been reported in the journal.
If you are of a certain age, you may have had measles as a child. Many of those born after the 1970s never got it thanks to vaccines. This condition is caused by a virus of the same name, which is one of the most infectious pathogens to this day. The World Health Organization estimates that nearly nine million people worldwide contracted measles in 2021, with the death toll reaching 128,000.
“Although it is available, the recent COVID-19 pandemic has set back vaccines, particularly in the Global South,” explains Yuta Shirogane, assistant professor at Kyushu University. “SSPE is a rare but potentially fatal condition caused by the measles virus. However, the normal measles virus does not have the ability to multiply in the brain, and therefore it is not clear how it causes encephalitis.”
The virus infects cells through a series of proteins that protrude from their surface. Normally, one protein will first facilitate the virus to attach to the cell surface, and then another surface protein will cause a reaction that allows the virus to enter the cell, resulting in an infection. Therefore, what a virus can or cannot infect can depend greatly on the cell type.
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“Normally, the measles virus only infects immune and epithelial cells, causing rashes and fever,” Shirogane continues. “Therefore, in patients with SSPE, the measles virus must have remained in their bodies and mutated, then acquired the ability to infect neurons. RNA viruses such as measles mutate and evolve at very high rates, but the mechanism of their evolution to infect neurons has been a mystery.” .
The key player in allowing the measles virus to infect a cell is a protein called a fusion protein, or F protein. They show that some mutations in the F protein put it into a “hyperplastic” state, allowing it to fuse into synapses and infect the brain.
In their latest study, the team analyzed the measles virus genome from SSPE patients and found that various mutations had accumulated in their F protein. Interestingly, some mutations may increase infection activity while others actually decrease it.
“It was amazing to see, but we found an explanation for this. When a virus infects a nerve cell, it infects it through ‘block transmission’, where multiple copies of the viral genome enter the cell,” Shirogane continues. “In this case, the genome encoding the mutant F-protein is transmitted simultaneously with the genome of the normal F-protein, and both proteins are likely to coexist in the infected cell.”
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Based on this hypothesis, the team analyzed the fusion activity of the mutant F proteins when the normal F proteins were present. Their results showed that the fusion activity of the mutant F protein is suppressed due to interference from normal F proteins, but this interference is overcome by the accumulation of mutations in the F protein.
In another case, the team found that a different set of mutations in the F protein lead to exactly the opposite result: a decrease in fusion activity. However, to their surprise, this mutation can actually cooperate with normal F proteins to increase fusion activity. Thus, even mutant F proteins that seem unable to infect neurons can infect the brain.
It is almost equivalent to the “survival of the fittest” model of viral replication. In fact, this phenomenon in which mutations interfere and/or cooperate with each other is called “sociology”. This is still a new concept, but viruses have been observed interacting with each other as a group. It’s an exciting prospect, Shirogane explains.
The team hopes their findings will help develop treatments for SSPE, as well as elucidate common evolutionary mechanisms for viruses that have infection mechanisms similar to measles such as novel coronaviruses and herpes viruses.
There are many mysteries in the mechanisms by which viruses cause disease. Since I’m a medical student, I’ve been interested to know how the measles virus causes SSPE. I’m glad we were able to clarify the mechanism of this disease,” concludes Shirogane.