Century-old lung sample helps pinpoint origin of measles, offers lessons for SARS-CoV-2 research

SYDNEY — Over the course of history, a host of infectious and deadly pathogens have jumped into the human population from animals. While SARS-CoV-2 is the latest virus to do so, there are many more ancient examples of this phenomenon. Measles virus, which is generally accepted to have emerged out of a spillover event from cattle to humans, is one of the oldest viruses known to infect humans. Thanks to genetic material recently recovered from a 100-year old lung specimen, a new study, published in Science, traces the emergence of measles to around 6th century BCE. That’s about 1,400 years earlier than current estimates.

The lung specimen was identified from among a collection of some 750 preserved organs curated by the famous German pathologist, Rudolf Virchow. It was housed at The Berlin Museum of Medical History at the Charité in Germany. The diseased lungs belonged to a 2-year-old girl who died of measles in 1912.

Using advanced next-generation sequencing techniques, an international team of scientists was able to reconstruct an almost-complete measles virus genome from the formalin-fixed lung tissue. Before this genome was sequenced, the oldest measles genome ever determined was from 1954.

“Obtaining genomic data from RNA viruses such as the measles virus, which degrade rapidly in the environment, continues to be extremely challenging,” says study co-author Simon Ho, an evolutionary expert from the University of Sydney in a statement. “The sequencing of this measles genome by Ariane Düx, Sébastian Calvignac-Spencer and their colleagues is a profound achievement.”

Lineage of measles

In order to get a better picture of the origin of measles, Düx and colleagues compared the 1912 measles virus sequence to the sequences of a number of other related measles viruses that reflected the currently known genetic diversity of the virus. They also compared it to the sequences of two closely-related cattle-infecting viruses, rinderpest virus (RPV) and Peste des petits ruminants virus (PPRV).

Using a series of evolutionary and molecular clock models, the scientists estimate the divergence date of measles and rinderpest at around 528 BCE. They speculate this may have coincided with the rise of large cities.

“For any particular pathogen, the timing of the jump must have occurred between two time points: when it split from its nearest known relative and when we look at the pathogen in humans and trace the lineages back to the common ancestor,” explained Ho.

Inclusion of the reconstructed 1912 measles virus sequence in the analysis was an important factor in pushing back the date of its common viral ancestor. That’s because measles has been the focus of large-scale vaccination efforts, which have had the effect of reducing genetic diversity of the virus. This means that a substantial number of viral lineages are now extinct and no longer available for analysis. Older viral genome sequences may therefore have the benefit of providing additional information about the evolutionary pathway of the virus.

How findings relate to coronavirus research

In a concurrently published Perspective in Science, Ho and co-author, Sebastián Duchêne, propose using a similar approach to refine existing data about the emergence of SARS-CoV-2. They postulate that, although the divergence between SARS-CoV-2 and its closest known relative, a coronavirus isolated from a horseshoe bat, likely happened several decades ago, the jump to humans probably happened more recently.

This gap in time poses a problem for identification of the host reservoir and the timescale for zoonotic spillover into humans. In the case of measles, tracing its emergence to an earlier date than previously thought led to the discovery of a strong correlation with the rise of populations large enough to support viral transmission. Ho and Duchêne state that additional genomic data from historical and ancient samples and better surveillance of viruses in wildlife could lead to improved understanding of how human pathogens emerge.

“It’s very difficult to pinpoint exactly when and where pathogens such as viruses and bacteria jump into humans. Sometimes these jumps happen and they fizzle out. But sometimes they take hold and spread across the globe,” says Ho. “More work needs to be done to understand the diversity of viruses and their distribution in wildlife.”

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