Reporter : Tang Feng
Publisher : China Science Daily
Translation, editing : Gan Yung Chyan
/ KUCINTA SETIA
Image : Specimens from the Berlin Medical History Museum, Germany. Photo credit: Navena Widulin
Measles is a highly contagious disease. Although it can be prevented by vaccines, it still greatly affects human health. Like many human diseases, measles originates in animals. Researchers have always suspected that an overflow of a cow-infected virus may have caused the disease, but the time and environment in which the overflown occurred is still controversial.
Recently, an international research team figured out when measles first appeared, and found that it may be related to the rise of big cities. Related papers are published in Science. Ariane Düx and others from the Highly Pathogenic Microbiology Epidemiology Project of the Robert Koch Institute in Germany performed genome sequencing of a measles strain in 1912 and reviewed the time when the virus may appear in humans. It dates back to the sixth century BC.
"Although people think that measles appeared after the Neolithic Age, it is unclear when it occurred. Our findings help to better understand the evolution of measles virus, the emergence of disease, and ultimately understand the important role played in the spread of the disease in human history." Düx said in an interview with China Science News.
Simon Ho, a professor at the University of Sydney, said, "RNA viruses such as measles virus can degrade rapidly in the environment, and obtaining their genomic data is a very challenging task. Therefore, this research is a major achievement in the sequencing of the measles genome. Helps to identify when humans have measles."
Ho et al. also suggested that similar refinement of research on when covid and other zoonotic diseases will appear will help to understand how these pathogens jump from animals to humans.
New clues hidden in ancient specimens
Measles is highly contagious, and once the infection is cleared, people have lifelong immunity to the disease. Düx said this means that the continued spread of the disease depends on a large number of human exposures, and these exposures did not exist before the Neolithic transition (probably not before 1000 BC).
However, historical records do not give a clear indication of when measles appears. In addition, studies have estimated that measles appeared in the Middle Ages. But the molecular clock models used in these studies are suspected of underestimating the more distant durations. Therefore, the Düx team used the modern clock model developed by Leuven University, which was specifically designed to correct this systematic underestimation.
The researchers found a well-preserved lung of a measles patient in the collection of the Berlin Medical History Museum. The lungs of this two-year-old patient who died in Berlin in 1912 have been "sleeping" in formalin.
The team successfully assembled almost the entire measles virus genome. This is also the genome sequencing of the oldest human infected RNA virus to date. "We are excited to find that it is possible to extract viral RNA from such an ancient specimen, and it is actually very easy to do. This opens up new prospects for RNA virus evolution research." The study co-corresponding author and responsible for sequencing gene sequences Sébastien Calvignac-Spencer said.
Thomas Schnalke, Head of the Berlin Medical History Museum, added, "This highlights the outstanding value of the collection of medical specimens, which are not only historical but also molecular archives."
The researchers then compared the measles genome of the 1912 sample with the genomes of 50 other viruses, including other measles strains, related rinderpest, and small ruminant pestiviruses, and reassessed the dates of measles and rinderpest virus differentiation. Strain virus family tree.
The researchers also estimated using the new molecular clock model. Philippe Lemey of the University of Leuven, responsible for developing the new model, said: "Previous studies using molecular clocks have placed the origin of measles in the Middle Ages, but these dates have not adequately explained the long-term evolutionary dynamics and greatly underestimated the age of the measles lineage. "
Crowd gathering virus migration
In the end, researchers believe that the differentiation of measles virus and rinderpest virus may occur in the 6th century BC, a period of population growth and the rise of large cities in Asia and Europe. Although the study could not clarify exactly where the virus differentiation took place, the time is roughly in line with the emergence of hundreds of thousands of large cities in China, India, North Africa and Europe.
"This time is more than 1,000 years earlier than previously thought. And, interestingly, it coincides with the time when the first human settlement was large enough to support the continued spread of the measles virus," Düx said.
The researchers pointed out that by observing the spread of measles in the island’s human community, it can be determined that measles cannot survive for a long time in a place with a population of less than 500,000. Because of its lifetime immunity, once everyone in the community has contracted measles, there are no more hosts for measles to survive and spread. Only in larger communities will there be enough new hosts to survive the virus.
In addition to crowd gathering, the researchers also emphasized the importance of virus migration shown by the measles virus. The most recent relative of measles virus is rinderpest virus, a pathogen that has now been eradicated, and it has caused massive deaths of cattle and wild ungulates in the past. It has long been assumed that their ancestors infected cows and eventually jumped into humans, resulting in the measles virus lineage.
Deducing the root of the virus epidemic
In fact, the transfer of microorganisms from one host species to another is a common cause of viral pandemics. This also applies to coronaviruses.
Ho told the China Science Daily that, as tracking measles research shows, the emergence of the disease is associated with the rise of large cities thousands of years ago, which also has implications for understanding coronaviruses and preventing pandemics. For example, the probability of a virus spreading between different species generally increases with the number of contacts, especially as human civilization is increasingly invading wildlife habitats.
Understanding the emergence and evolution of human pathogens plays a key role in predicting the path of disease outbreaks. Phylogenetic methods provide a series of insights into the evolutionary dynamics of pathogen genomes. In many cases, phylogenetic methods can use the sampling date of the genome to reconstruct the evolutionary time scale of viruses, bacteria, and other pathogens.
Researchers say that for any particular pathogen, its jumping and transmission between different hosts must occur between two points in time: it is separated from the nearest relatives known, and people begin to observe human pathogens and trace their common ancestors Time.
Ho and Sebastián Duchêne of the University of Melbourne wrote in a review article published in Science during the same period that the chronological analysis of related pathogens in the New Coronary Pneumonia pandemic has attracted much attention. "People already know that one of the novel coronaviruses' close relatives is a coronavirus in the genus Helicoptera, but the two viruses were isolated decades ago. The current common ancestor of the novel coronavirus sample genome can be traced back to from the end of November to the beginning of December 2019. The time gap between these two events hinders the time to identify the novel coronavirus host and the virus spilled into the human host."
"Viruses can spread between species that do not normally appear in the wild at the same time, so more work needs to be done to understand the diversity of the virus and its distribution in wild animals." Ho said, "from historical and ancient samples further genomic data, as well as a more comprehensive and in-depth investigation of viruses lurking in wild animals, will improve our understanding of the environment and mechanisms in which pathogens appear in the host."
Related paper information: https://doi.org/10.1126/science.aba9411
https://doi.org/10.1126/science.abc5746
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