Japanese researchers have revealed the mechanism by which the measles virus causes subacute sclerosing panencephalitis (SSPE).
The normal form of the measles virus cannot infect the nervous system, but researchers found that if the virus persists in the body, it can mutate a key protein that controls how cells are infected. Did. Mutated proteins can interact with normal forms and infect the brain.Their findings were reported in the journal scientific progress.
If you are of a certain age, you may have had measles as a child. Many people born since the 1970s have never been infected thanks to vaccines. This condition is caused by the homonymous virus, which he is one of the most contagious pathogens to date. The World Health Organization estimates that about 9 million people worldwide will be infected with measles in 2021, with the death toll reaching her 128,000.
Despite being available, the recent COVID-19 pandemic has set back vaccination, especially in the global South. SSPE is a rare but fatal condition caused by the measles virus. However, the normal measles virus is incapable of replicating in the brain, so the mechanism by which it causes encephalitis is unknown. “
Yuta Shirogane, Assistant Professor, Faculty of Medicine, Kyushu University
Viruses infect cells through a series of proteins protruding from their surface. Usually, one protein first facilitates attachment of the virus to the cell surface, then another surface protein triggers a reaction that allows the virus to enter the cell and cause infection. Therefore, what a virus can and cannot infect depends largely on the cell type.
“Usually, the measles virus infects only immune cells and epithelial cells, causing fever and rash,” Shirogane continues. “Thus, in patients with SSPE, the measles virus must have acquired the ability to persist, mutate, and infect neurons. RNA viruses like measles mutate and evolve at a very high rate. However, the mechanism of how it evolved and infected the neuron was a mystery.”
The main role that allows the measles virus to infect cells is a protein called a fusion protein or F protein. state, fuses to neural synapses and infects the brain.
In the latest study, the team analyzed the genomes of the measles virus in SSPE patients and found that various mutations accumulated in the F protein. Interestingly, certain mutations increased infectious activity, while others actually decreased it.
“This was surprising, but we found an explanation. When a virus infects a neuron, multiple copies of the viral genome enter the cell through ‘batch transfer,'” Shirogane continued. increase. “In this case, the genome encoding the mutant F protein could be co-transmitted with the genome of the normal F protein, and both proteins co-exist within the infected cell.”
Based on this hypothesis, the team analyzed the fusion activity of mutant F proteins in the presence of normal F proteins. Their results showed that the fusion activity of the mutant F protein was suppressed by interference from the normal F protein, but that interference was 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 had the exact opposite result: reduced fusion activity. Surprisingly, however, this mutation can actually cooperate with the normal F protein to enhance fusion activity. Therefore, even mutant F proteins that appear unable to infect neurons can still infect the brain.
“This almost goes against the ‘survival of the fittest’ model of viral propagation. In fact, this phenomenon of mutations interfering and/or cooperating with each other has been termed ‘socivirology’. It’s still a new concept, but I’m really looking forward to seeing how the viruses interact with each other like groups,” explains Shirogane.
The team hopes their results will help develop treatments for SSPE, and will also elucidate evolutionary mechanisms common to viruses with similar mechanisms of transmission to measles, such as the novel coronavirus and herpes virus. I hope that
“There are many mysteries about how viruses cause disease. As a medical student, I was interested in how the measles virus causes SSPE. I think,” concludes Shirogane. .
Shirogane Yoshi and others. (2023) Population fusion activity determines the neurotropism of Enbloc-infecting enveloped viruses. scientific progress. doi.org/10.1126/sciadv.adf3731.