NEW YORK – An international team led by University of Cambridge investigators has used ancient DNA analyses to retrace the history and spread of herpes simplex virus 1 (HSV-1), the culprit behind lip sores commonly known as cold sores. Changes in the practice of kissing, they speculated, may have played a role in this.
"Every primate species has a form of herpes, so we assume it has been with us since our own species left Africa," co-senior and co-corresponding author Christiana Scheib, head of Tartu University's ancient DNA lab and a research fellow at the University of Cambridge's St. John’s College, said in a statement. "However, something happened around 5,000 years ago that allowed one strain of herpes to overtake all others, possibly an increase in transmissions, which could have been linked to kissing."
As they reported in Science Advances on Wednesday, Scheib and her colleagues used metagenomic sequencing to screen thousands of archaeological samples collected over time from sites across Europe, uncovering four HSV-1-containing tooth samples reaching back to the Iron Age. A single sample came from an infected man living in the Ural Mountain region of Russia some 1,500 years ago, while three samples spanning the 6th to 17th centuries came from infected individuals in the UK or Holland.
"Facial herpes hides in its host for life and only transmits through oral contact, so mutations occur slowly over centuries and millennia," co-senior and co-corresponding author Charlotte Houldcroft, a genetics researcher at the University of Cambridge, said in a statement. "We need to do deep time investigations to understand how DNA viruses like this evolve."
"Only genetic samples that are hundreds or even thousands of years old will allow us to understand how DNA viruses such as herpes and monkeypox, as well as our own immune systems, are adapting in response to each other," she explained.
With that in mind, the team turned to targeted capture sequencing to generate whole-genome sequences for three of the HSV-1 isolates and a partial genome sequence for another isolate. They then analyzed these ancient European HSV-1 sequences in combination with corresponding human host genomes as well as sequences generated for ancient and modern humans and HSV-1 isolates assessed in the past.
Their genomic and phylogenetic analyses suggested that HSV-1 lineages, or phylogroup clusters, that continue to spread in humans around the world likely originated in the Eurasian Steppe some 4,600 to 6,100 years ago, spreading to Europe with Bronze Age migrations around 4,700 years ago, the researchers explained.
They speculated that the explosion of the predominant HSV-1 strain may have gotten a boost from the adoption of kissing — first documented in South Asia during the Bronze Age — as a more widespread cultural practice.
"Research has shown that there were migration(s) from the Eastern European Steppe region into the rest of Europe and likely an increase in population density during the Bronze Age," the authors explained. "The primary mode of HSV-1 transmission is vertical, from parent to child; however, the addition of lateral transmission as population density increased during the Bronze Age, potentially linked to the introduction of new cultural practices such as the advent of sexual-romantic kissing … may have contributed to a shift in the dominant lineages, which have continued to circulate to this day."
The investigators noted that future studies focused on still other HSV-1 isolates in other ancient humans or archaic hominins from sites in Asia, Africa, and other parts of the world will likely lead to a clearer understanding of the virus's evolutionary history and the forces that allowed it to latch on in humans, globally infecting roughly two of every three adults under 50.
"Given the high prevalence of HSV-1 infections in human populations today and the pathophysiology of the virus, HSV-1 should be abundant in archaeological teeth," the authors wrote, adding that "[f]urther ancient genomes, for example from the Neolithic period, may further revise our understanding of the evolutionary history of this today ubiquitous pathogen and continue to inform on the nature of its association with human hosts."