13-05-2025
Secret to treating HIV came thousands of years before virus ever appeared. How?
On June 5, 1981, the Centers for Disease Control and Prevention reported five cases of an unknown infection leading to a rare kind of pneumonia.
All five men were previously young and healthy, and additional infections indicated their immune systems weren't working. Two of them had already died.
It would be another two years before French researchers would identify a retrovirus as the cause of AIDS, or acquired immunodeficiency syndrome, according to the CDC.
It would be another three years before that virus would get its name HIV, or human immunodeficiency virus, the agency said.
In the first 10 years of the HIV/AIDS epidemic, 8-10 million adults were infected worldwide, according to a 1991 report from the CDC. It became the second leading cause of death among men ages 25 to 44, and nearly 200,000 cases were reported in the United States, primarily among members of the gay community.
Years after the virus was first identified, in 1996, researchers discovered there was a group of people with a genetic mutation that made them resistant or even immune from HIV, and this mutation was present in between 18% and 25% of the population of Denmark, according to a May 9 news release from the Novo Nordisk Foundation Center for Basic Metabolic Research.
But where in human history did the mutation originate? And how did a thousands-of-years-old mutation survive to fight a modern-day disease?
Researchers asked and answered these questions in a new study published May 5 in the peer-reviewed journal Cell.
What does the mutation do?
Human immunodeficiency virus, or HIV, is a virus that destroys human T-cells, the parts of the body that fight infection in your immune system, according to the Cleveland Clinic. The virus then leaves your body exposed to even minor illnesses, leading to causes of death from things like pneumonia or bronchitis.
You can carry HIV without experiencing symptoms, or if your condition worsens, you can develop acquired immunodeficiency syndrome, or AIDS, according to the Cleveland Clinic.
Those with the genetic mutation have what is called a '32-bp deletion,' which means the gene known as chemokine receptor 5, or CCR5, isn't fully expressed, according to the study. This gene partially regulates the inflammatory response of the immune system, researchers said, so those with the mutation did not react to HIV the same way, preserving their T-cells and fighting infection as normal.
The mutation has been used as the key to multiple HIV treatments, including transplanting donor cells, according to the study. This includes a recent case where donor cells transplanted into a female patient led to her being potentially 'cured' of the disease.
Previous research tracking the CCR5 mutation narrowed its origin down to European groups between 5250 and 1690 B.C., and there were spikes when more people had the mutation during the Black Death pandemic and during the late medieval period, according to the study.
But this wasn't back far enough.
Finding the source
Researchers analyzed the genetic code of 934 ancient human remains and compared it to 2,504 present-day genomes, according to the study. This allowed the team to narrow the field to a more specific time and region of the world.
From this genetic data, the researchers developed an AI method that could identify the mutation in ancient bones, according to the release.
'By looking at this large dataset, we can determine where and when the mutation arose. For a period, the mutation is completely absent, but then it suddenly appears and spreads incredibly quickly,' study author Kirstine Ravn said in the release. 'When we combine this with our knowledge of human migration at the time, we can also pinpoint the region where the mutation originated.'
All lines came back to one point — a single person living close to the Black Sea as many as 9,000 years ago, which includes the early Stone Age and the Viking Age, researchers said. All modern-day carriers of the mutation are descendants of this individual.
'It turns out that the variant arose in one individual who lived in an area near the Black Sea between 6,700 and 9,000 years ago,' study author Simon Rasmussen said in the release. 'HIV is a relatively new disease — less than 100 years old — so it's almost coincidental and very fascinating that a genetic variation that arose thousands of years ago also protects against a modern virus like HIV.'
An ancient coincidence
It is merely a coincidence that the ancient mutation has the HIV-preventing effect now, researchers said, but the general impact on the immune system caused by the mutation may be why it survived in generation after generation.
'People with this mutation were better at surviving, likely because it dampened the immune system during a time when humans were exposed to new pathogens,' study author Leonardo Cobuccio said in the release.
Researchers said as people transition from widespread hunter and gatherer communities to close-knit agricultural communities, they are exposed to new infectious diseases.
The mutation disrupts the immune response, which they say sounds bad, but would actually prevent diseases that cause extreme damage to the immune system from being so effective, according to the release.
'An overly aggressive immune system can be deadly — think of allergic reactions or severe cases of viral infections like COVID-19, where the immune system often causes the damage that kills patients,' researchers explained.
Those with the mutation would have had a 'more balanced immune system,' which would have been 'advantageous' and thus allowed the mutation to persist to modern day, according to the release.
The research was conducted through the Novo Nordisk Foundation Center for Basic Metabolic Research, at the University of Copenhagen in Denmark.
The research team includes Ravn, Cobuccio, Rasmussen, Rasa Audange Muktupavela, Jonas Meisner, Lasse Schnell Danielsen, Michael Eriksen Benros, Thorfinn Sand Korneliussen, Martin Sikora, Eske Willerslev, Morten E. Allentoft and Evan K. Irving-Pease.
