Prehistoric roots of ‘cold sore’ virus traced through ancient herpes DNA

Ancient genomes of the herpes virus that commonly causes lip lesions – and currently infects some 3.7 billion people worldwide – have been discovered and sequenced for the first time by an international team of scientists led by the University of Cambridge.

The latest research suggests that the strain of the HSV-1 virus that causes facial herpes as we know it today emerged around 5,000 years ago, following extensive migrations from the age of bronze to Europe from the Eurasian steppe grasslands and associated population booms that resulted in high transmission rates.

Herpes has a history that dates back millions of years, and forms of the virus infect species ranging from bats to coral. Despite its contemporary prevalence in humans, however, scientists say ancient examples of HSV-1 were surprisingly hard to find.

The authors of the published study in the review Scientists progresssay that the Neolithic flourishing of facial herpes detected in ancient DNA may have coincided with the advent of a new cultural practice imported from the Orient: romantic and sexual kissing.

“The world has seen COVID-19 mutate at a rapid pace over weeks and months. A virus like herpes evolves on a much larger time scale,” said co-lead author Dr Charlotte Houldcroft, from Cambridge’s Department of Genetics.

“Facial herpes hides in its host for life and is only transmitted by oral contact, so mutations occur slowly over centuries and millennia. We need to carry out in-depth investigations to understand how viruses to DNA like this evolve,” she said. “Previously, the genetic data for herpes only goes back to 1925.”

The team succeeded in tracking down herpes in the remains of four individuals spanning a thousand year period and extracting viral DNA from the roots of the teeth. Herpes often manifests as mouth infections: at least two of the ancient corpses suffered from gum disease and a third smoked tobacco.

The oldest sample came from an adult male discovered in the Ural mountain region of Russia, dating to the Late Iron Age around 1,500 years ago.

Two other samples were local to Cambridge, UK. A woman from an ancient Anglo-Saxon cemetery a few miles south of town, dating from 6-7e centuries of our era. The other a young adult male in his late 14’se century, buried in the grounds of Cambridge’s Medieval Charitable Hospital (later to become St. John’s College), who had suffered horrific abscessed teeth.

The final sample came from a young adult male excavated in Holland: an avid clay pipe smoker, most likely slaughtered in a French attack on his village on the banks of the Rhine in 1672.

“We sifted through ancient DNA samples from around 3,000 archaeological finds and only obtained four cases of herpes,” said co-lead author Dr Meriam Guellil, of the Genomics Institute of the University of Tartu.

“By comparing ancient DNA with herpes samples from the 20e century, we were able to analyze the differences and estimate a mutation rate, and therefore a timeline of the evolution of the virus,” said co-lead author Dr Lucy van Dorp, from the Institute of Genetics of the ‘UCL.

Co-lead author Dr Christiana Scheib, a researcher at St. John’s College, University of Cambridge and director of the Ancient DNA Laboratory at the University of Tartu, said: ‘Every species of primate has a form of herpes, so we assume it has been with us since our own species left Africa.

“However, something happened about five thousand years ago that allowed one strain of herpes to overtake all others, possibly an increase in transmissions, which could have been linked to kissing.”

Researchers point to the earliest known record of kissing being a Bronze Age manuscript from South Asia, and suggest the custom – far from universal across human cultures – may have traveled west. with migrations to Europe from Eurasia.

In fact, centuries later, Roman Emperor Tiberius attempted to ban kissing at official functions to prevent the spread of disease, an edict that may have been linked to herpes. However, for most of human prehistory, the transmission of HSV-1 would have been “vertical”: the same strain passing from the infected mother to the newborn.

According to the World Health Organization, two-thirds of the world’s population under the age of 50 are now carriers of HSV-1. For most of us, the occasional sores on the lips that result are embarrassing and uncomfortable, but in combination with other conditions – sepsis or even COVID-19, for example – the virus can be deadly. In 2018, two women died of HSV-1 infection in the UK following cesarean deliveries.

“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, adapt to each other,” Houldcroft said.

The team would like to trace this hardy primordial disease even deeper in time, to investigate its infection of early hominids. “Neanderthal herpes is my next mountain to climb,” Scheib added.

– This press release was originally published on the University of Cambridge website

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