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New high-resolution structures of measles virus enzyme could lead to protective measures
May 30—Using high-resolution cryo-electron microscopy (cryoEM), researchers at The Hormel Institute, University of Minnesota, have revealed the first high-resolution renderings of the measles virus's (MeV) polymerase. This enzyme is crucial for the virus's ability to hijack cells and make copies of itself, which is one aspect that makes the virus so effective at infecting people and spreading throughout the body.
For a virus that's been documented since at least the ninth century, there is still plenty we have to learn about the measles virus and how it operates, Associate Professor Bin Liu, PhD, explained as he discussed his new study published in Nature Communications.
"Even well-known viruses like measles still have uncharted molecular terrain, and illuminating its structure provides valuable insights for therapeutic development," Liu said.
By revealing measles' structure, Liu, along with Postdoctoral Researchers Dong Wang, PhD, and Ge Yang, PhD, have unlocked valuable insights that could help other researchers develop preventative and therapeutic measures to combat this deadly virus that can cause complications ranging from pneumonia to ear infections to encephalitis (inflammation of the brain).
"Although an effective vaccine is available, recent measles outbreaks highlight the urgent need for alternative antiviral treatments," Liu said. "Because the polymerase is essential for viral genome replication, it represents a critical target for antiviral intervention."
The study presents two new, distinct renderings of MeV polymerase complexes known as Lcore-P and Lfull-P-C.
According to Liu, one of the most intriguing findings is the structural role of the measles virus C protein in forming the Lfull-P-C complex with two other proteins, L and P. This is surprising because the C protein was traditionally seen as a regulatory protein, not part of its core replication machinery. Now, it's shown to physically bridge and modulate the L protein's activity, potentially influencing how efficiently the virus replicates.
Additionally, the study shows that the C protein widens the polymerase's RNA channel in the polymerase, possibly enhancing the processivity of RNA synthesis. That kind of physical alteration, revealed via cryoEM at near-atomic resolution, is a remarkable mechanistic insight. It suggests that the measles virus has evolved an elegant, multi-protein solution for efficient replication inside host cells. This kind of structural adaptation is a biological engineering marvel, and it highlights how even simple viruses can have complex, dynamic protein machinery.
By revealing detailed interactions within the Lfull-P-C complex, the paper opens doors for next-generation antiviral drug designs that halt viral replication.
"This shifts the measles conversation from 'solved by vaccines' to 'still relevant for therapeutic innovation,'" Liu concluded.
