Mechanism behind measles virus causing fatal encephalitis unfolded in Japanese study - Video

Researchers in Japan have uncovered the mechanism for how the measles virus can cause subacute sclerosing panencephalitis, or 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. The mutated proteins can interact with its normal form, making it capable of infecting the brain. Their findings were reported in the journal Science Advances.

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 'hyperfusongenic' state, allowing it to fuse onto neural synapses and infect the brain.

In their latest study, the team analyzed 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. Based on this hypothesis, the team analyzed the fusion activity of mutant F proteins when normal F proteins were present. 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 team 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 actually 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.

Reference:

Collective Fusion Activity Determines Neurotropism of an en Bloc Transmitted Enveloped Virus,Science Advances,10.1126/sciadv.adf3731