Measles virus can develop mutations that cause fatal SSPE
Posted: 2 February 2023 | Izzy Wood (Drug Target Review) | No comments yet
Japanese researchers find a new mechanism for how the measles virus can cause a rare but fatal neurological disorder: subacute sclerosing panencephalitis (SSPE).
Researchers from Kyushu University in Japan, have uncovered the mechanism for how the measles virus can cause subacute sclerosing panencephalitis (SSPE)- a rare but fatal neurological disorder that can occur several 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, reported in the journal Science Advances. The mutated proteins can interact with its normal form, making it capable of infecting the brain.
“Despite its availability, the recent COVID-19 pandemic has set back vaccinations, especially in the Global South,” explained Assistant Professor Yuta Shirogane from Kyushu University’s Faculty of Medical Sciences.
“SSPE is a rare but fatal condition caused by the measles virus. However, the normal measles virus does not have the ability to propagate in the brain, and thus it is unclear how it causes encephalitis.”
“Usually, the measles virus only infects your immune and epithelial cells, causing the fever and rash,” continued Shirogane. “Therefore, in patients with SSPE, the measles virus must have remained in their body and mutated, then gained the ability to infect nerve cells. RNA viruses like measles mutate and evolve at very high rates, but the mechanism of how it evolved to infect neurons has been a mystery.”
The key player in allowing the measles virus to infect a cell is a protein called fusion protein, or F protein. In the team’s previous studies, they showed that certain mutations in the F protein puts it in a ‘hyper-fusongenic’ state, allowing it to fuse onto neural synapses and infect the brain.
In their latest study, the team analysed the genome of the measles virus from SSPE patients and found that various mutations had accumulated in their F protein. Interestingly, certain mutations would increase infection activity while others actually decreased it.
“When the virus infects a neuron, it infects it through ‘en bloc transmission,’ where multiple copies of the viral genome enter the cell. 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.” added Shirogane.
Their results showed that fusion activity of a mutant F protein is suppressed due to interference from the normal F proteins, but that interference is overcome by the accumulation of mutations in the F protein.
In another case, the researchers found that a different set of mutations in the F protein results in a completely opposite result: a reduction in fusion activity. However, to their surprise, this mutation can cooperate with normal F proteins to increase fusion activity. Thus, even mutant F proteins that appear to be unable to infect neurons can still infect the brain.
The team hopes that their results will help develop therapeutics for SSPE, as well as elucidate the evolutionary mechanisms common to viruses that have similar infection mechanisms to measles such as novel coronaviruses and herpesviruses.
Central Nervous System (CNS), Disease Research, Protein, RNAs, Targets, Virology
Measles, subacute sclerosing panencephalitis (SSPE)