Human genome is 8% viruses – and here’s why it matters

(ORDO NEWS) — Approximately 8% of our genome is the remnants of ancient viruses that once entered the body of our ancestors.

Remnants of ancient viral epidemics, in the form of viral DNA sequences embedded in our genomes, are still active in healthy people, according to a new study that my colleagues and I recently published.

Human endogenous retrovirus (HERV) remnants make up approximately 8% of the human genome. They are the result of diseases from which the ancient ancestors of man suffered millions of years ago. And these viruses have become part of the human genome because of the way they replicate.

Like modern HIV, these ancient retroviruses had to insert their genetic material into the host genome in order for the replication process to take place. Typically, such virus genetic material is not passed down from generation to generation.

But some ancient retroviruses have acquired the ability to infiltrate primordial germ cells, such as eggs or sperm cells, which actually pass on their DNA to future generations.

By invading primordial germ cells, these retroviruses have managed to take root in the genomes of human ancestors over several million years, and now they may even influence how researchers test for certain diseases.

Active genes of viruses in the human genome

Viruses introduce their genome into host cells in the form of a provirus. Currently, there are about 30 different types of human endogenous retroviruses in humans, that is, the human genome contains more than 60 thousand proviruses.

These proviruses can tell the long story of the many pandemics that humanity has had to go through in the course of evolution.

Scientists believe that numerous populations were once infected with these viruses, since their DNA sequences were fixed not only in the human genome, but also in the genomes of chimpanzees, gorillas and other primates.

Research conducted in our and other laboratories has shown that HERV genes are active in diseased tissues such as tumor tissues, as well as during human embryonic development. But how active HERV genes are in healthy tissues is still largely unknown.

To answer this question, our lab decided to focus on one group of HERVs called HML-2. It is the most recent active group of all HERVs – these viruses disappeared less than 5 million years ago. But even now, some of its proviruses that persist in the human genome show the ability to produce viral proteins.

We analyzed the genetic material in a database containing more than 14,000 tissue samples taken from a wide variety of organs and parts of the body. We searched for sequences corresponding to every HML-2 provirus in the human genome and found 37 different HML-2 proviruses that were still active.

The 54 tissue samples we analyzed had some evidence of activity from one or more of these proviruses. Moreover, all tissue samples also contained genetic material from at least one provirus that still had the ability to produce viral proteins.

The role of HERV viruses in maintaining health and developing diseases

The fact that thousands of pieces of ancient viruses are still present in the human genome and can even produce proteins is of great interest to scientists, especially since viruses similar to them, which remain active to this day, can cause such diseases, like breast cancer and an AIDS-like disease in animals.

Whether the genetic remains of human endogenous retroviruses are still capable of causing disease in humans is still unclear.

Scientists have found particles similar to HML-2 viruses in cancer cells, and the presence of HERV genetic material in affected tissues has been linked to the development of diseases such as amyotrophic lateral sclerosis, multiple sclerosis, and even schizophrenia.

Our study takes a fresh look at this data, showing that HERV genes are present even in healthy tissues. This means that the presence of HERV RNA may not be sufficient to link the virus to the development of a particular disease.

More importantly, it also means that HERV genes or proteins may no longer be suitable drug targets. For HERV, scientists have tested a range of drugs, including antiretrovirals, antibodies for breast cancer, and T-cell therapy for melanoma.

In the application of treatments using HERV genes as a cancer biomarker, their activity in healthy tissues must also be taken into account.

On the other hand, our study shows that HERVs may even be beneficial to humans. The best-known HERV to have invaded human and animal genomes is syncytin, which is a gene derived from an ancient retrovirus that plays an important role in the formation of the placenta.

Pregnancy in all mammals depends on the protein that this gene encodes.

Meanwhile, mice, cats and sheep have also found a way to use endogenous retroviruses to defend themselves against the original ancient virus that created them.

While these invading viral DNA sequences cannot force the host to recreate a full-fledged virus, enough of these pieces circulate in the host’s body to prevent their ancestor virus from replicating if the host encounters it.

Scientists suggest that one HERV may have played a protective role among humans millions of years ago. Our study shows that some other HERVs could have entered the human genome and then been used by the human body for the same purpose.

Many more unknown

Our study demonstrated levels of HERV activity in the human body that were previously unknown, and as a result it raised as many questions as it answered.

We still have much to learn about the ancient viruses that persist in the human genome, including whether their presence benefits humans and what mechanisms are responsible for their activity. In addition, it will be necessary to study whether these genes can trigger the production of viral proteins.

When we answer these questions, we will be able to understand the previously unknown functions of the genes of these ancient viruses and help scientists figure out how the human body responds to evolution, keeping echoes of ancient pandemics inside.

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