Ancient genomes from the herpes virus uncovered and sequenced for the first time

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

Human herpes simplex virus 1 (HSV-1), a life-long infection spread by oral contact, infects most adults globally. It commonly causes lip sores. Following primary infection, the virus becomes latent in sensory neurons. The virus can reactivate when triggered by psychological or physiological stress, resulting in recurrent labial lesions.

The latest research by an international team of scientists led by the University of Cambridge suggests that the HSV-1 virus as we know it today arose around five thousand years ago, in the wake of vast Bronze Age migrations into Europe from the Steppe grasslands of Eurasia, and associated population booms that drove rates of transmission.

Scientists uncovered and sequenced ancient genomes from the herpes virus for the first time. Herpes has been around for millions of years and affects various creatures, from coral to bats. Despite the fact that HSV-1 is so common in humans now, scientists have found that HSV-1 in the past has been unexpectedly difficult to identify.

Scientists noted, “The Neolithic flourishing of facial herpes detected in the ancient DNA may have coincided with the advent of a new cultural practice imported from the east: romantic and sexual kissing.”

Co-senior author Dr. Charlotte Houldcroft from Cambridge’s Department of Genetics said, “The world has watched COVID-19 mutate rapidly over weeks and months. A virus like herpes evolves on a far grander timescale.”

“Facial herpes hides in its host for life and only transmits through oral contact, so mutations occur slowly over centuries and millennia. We need deep investigations to understand how DNA viruses like this evolve. Previously, genetic data for herpes only went back to 1925.”

young adult male
One of the samples of ancient herpes DNA used in the study came from a male of 26-35 years old, excavated near the banks of the Rhine. The man was a fervent smoker of clay pipes. Traces of the habit are visible in multiple places on the teeth, where the hard clay pipe, usually put in the same place in the mouth, has worn the teeth. CREDIT: Dr Barbara Veselka

By extracting viral DNA from tooth roots, scientists could identify herpes in the remains of four people that date back more than a thousand years. As herpes often flares up with mouth infections, at least two ancient cadavers also had gum disease, and third smoked cigarettes. The oldest sample came from an adult male excavated in Russia’s Ural Mountains region, dating from the late Iron Age around 1,500 years ago.

Co-lead author Dr. Meriam Guellil from Tartu University’s Institute of Genomics said, “We screened ancient DNA samples from around 3,000 archaeological finds and got just four herpes hits.”

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

Co-senior author Dr. Christiana Scheib, Research Fellow at St. John’s College, University of Cambridge, and Head of the Ancient DNA lab at Tartu University, said: “Every primate species has a form of herpes, so we assume it has been with us since our species left Africa.”

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

Scientists noted, “The earliest known record of kissing is a Bronze Age manuscript from South Asia, and suggest the custom – far from universal in human cultures – may have traveled westward with migrations into Europe from Eurasia.”

In fact, centuries later, the Roman Emperor Tiberius made a possible herpes-related decree that attempted to forbid kissing at official gatherings to stop the spread of the disease. HSV-1 transmission would have been “vertical” over most of human prehistory, spreading from an infected mother to a newborn child.

According to the World Health Organisation, two-thirds of the global population under the age of 50 now carry HSV-1. For most of us, the occasional lip sores that result are embarrassing and uncomfortable, but in combination with other ailments – sepsis or even COVID-19, for example – the virus can be fatal. In 2018, two women died of HSV-1 infection in the UK following Caesarean births.

Houldcroft said, “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 immune systems, adapt in response to each other.”

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

Journal Reference:

  1. Meriam Guellil et al. Ancient herpes simplex 1 genomes reveal recent viral structure in Eurasia. Science Advances, 27 Jul 2022. Vol 8, Issue 30. DOI: 10.1126/sciadv.abo4435

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