The Measles Virus May Be Older Than Previously Believed

Measles is a highly contagious infectious disease that despite being vaccine-preventable still imposes a tremendous burden on human health. Like many human diseases, measles originated in animals. A spill-over of a cattle-infecting virus, the common ancestor to both measles virus and its closest relative, rinderpest virus, likely gave rise to the disease. The timing and circumstances of this important host switch, however, are still debated.

A study published in Science by researchers from the Robert Koch Institute, the KU Leuven, the Berlin Museum of Medical History at the Charité, the University of Oklahoma, and the University of California in Los Angeles now reveals that the measles virus may have emerged as early as the 6^th century BCE.

Scientists involved in the study started by analyzing a formalin-fixed lung from a 2-year-old measles patient that died in 1912 in Berlin, found in the collection of the Berlin Museum of Medical History. The team succeeded in assembling nearly the entire measles virus genome - notably, the oldest human-infecting RNA virus genome sequenced to date.

“We were thrilled to find that recovery of viral RNA from such an old specimen was possible and, actually, quite an easy thing to do. This opens new perspectives for the study of RNA virus evolution,” says Sébastien Calvignac-Spencer from the Robert Koch Institute, whose team sequenced the genome. Thomas Schnalke, the head of the Berlin Museum of Medical History, adds, “this underlines the outstanding value of medical specimen collections, which are not only historical but also molecular archives.”

In a second step, the 1912 genome, coupled with already available genomic data from additional measles strains and the related rinderpest and Peste des petits ruminants viruses, served as the basis to reassess the divergence date of measles and rinderpest viruses. This date marks the earliest possible emergence of the measles virus and was estimated using advanced molecular clock modeling.

“Previous studies using molecular clocks have placed the origin of measles in medieval times, but these datings did not appropriately account for long-term evolutionary dynamics and significantly underestimated the age of the measles lineage,” says Philippe Lemey from the KU Leuven, whose team developed new models aimed at avoiding such biases.

The new divergence estimate falls into the 6^th century BCE, a period marked by growing populations and the rise of large cities both in Europe and Asia. Measles requires large, connected populations for undisrupted circulation, which likely did not exist prior to this period.

Kyle Harper, a historian from the University of Oklahoma says “Of course we cannot say for sure if measles emerged in humans shortly after divergence and if that was linked to demographic change, but it is certainly a plausible scenario that can no longer be excluded.”