From NewsDesk @bactiman63
Japanese researchers have uncovered a mechanism for how the measles virus can cause subacute sclerosing panencephalitis, or SSPE, a rare but fatal neurological disorder that can appear years after a measles infection.
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 they infect cells. The mutated proteins can interact with its normal form, allowing it to infect the brain. Their findings were reported in the journal.
If you are of a certain age, you may have contracted measles as a child. Many born after the 1970s never got it thanks to vaccines. The condition is caused by a virus of the same name, which is still one of the most contagious pathogens today. The World Health Organization estimates that in 2021, measles infected nearly nine million people worldwide, with 128,000 deaths.
“Despite its availability, the recent COVID-19 pandemic has slowed vaccination, especially in the Global South,” explains Yuta Shirogane, an assistant professor at Kyushu University. “SSPE is a rare but fatal condition caused by the measles virus. However, the normal measles virus does not have the ability to spread in the brain, so it is not clear how it causes encephalitis.’
The virus infects cells through a series of proteins that protrude from its surface. Usually, one protein first facilitates the attachment of the virus to the cell surface, then another surface protein causes a reaction that admits the virus into the cell, leading to infection. Therefore, what a virus can or cannot infect can depend largely on the type of cell.
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“The measles virus usually only infects your immune and epithelial cells and causes a rash and fever,” Shirogane continues. “Therefore, in patients with SSPE, the measles virus had to remain in their body and mutate, then acquire the ability to infect nerve cells. RNA viruses such as measles mutate and evolve at very high rates, but the mechanism by which they evolved to infect neurons is a mystery.
The key player that allows the measles virus to infect a cell is a protein called the fusion protein, or F protein. They showed that certain mutations in the F protein put it in a “hyperfusogenic” state, allowing it to fuse to nerve synapses and infect the brain.
In their latest study, the team analyzed the measles virus genome from patients with SSPE and found that various mutations had accumulated in their F protein. Interestingly, some mutations would increase infection activity while others actually decreased it.
“It was surprising, but we found an explanation. “When a virus infects a neuron, it infects it by ‘en bloc transfer,’ where many copies of the viral genome enter the cell,” Shirogane continues. “In this case, the genome encoding the mutant F protein is transferred at the same time as 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 normal F proteins were present. Their results showed that the fusion activity of the mutant F protein is suppressed due to interference with normal F proteins, but that the 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 resulted in quite the opposite result: reduced fusion activity. However, to their surprise, this mutation can actually work with normal F proteins to increase fusion activity. Thus, even mutant F proteins that appear unable to infect neurons can still infect the brain.
“It almost contradicts the ‘survival of the fittest’ model of viral spread. In fact, this phenomenon of mutations interfering and/or cooperating with each other is called ‘sociovirology’. It’s still a new concept, but viruses have been observed to interact with each other they make an impact as a group. It’s an exciting prospect,” explains Shirogane.
The team hopes their results will help develop therapeutics for SSPE, as well as elucidate evolutionary mechanisms common to viruses that have similar infectious mechanisms to measles, such as novel coronaviruses and herpesviruses.
“The mechanisms by which viruses cause disease are many mysteries. Being a medical student, I was interested in how the measles virus causes SSPE. I am glad that we have succeeded in elucidating the mechanism of this disease,” concludes Shirogane.
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