Humans are 8% viruses – how these ancient invaders still control us today

Remains of the ancient Viral pandemics in the form of viral DNA sequences embedded in our genomes are still active in healthy people, according to new research that my colleagues and I recently published.

HERVs, or Human Endogenous Retroviruses, make up about 8% of the human genome, left over from infections that humanity’s primate ancestors suffered from millions of years ago. They became part of the human genome because of the way they replicate.

Like modern HIV, these ancient retroviruses had to insert their genetic material into their host’s genome to replicate. Usually, this type of viral genetic material is not passed down from generation to generation. But some ancient retroviruses have acquired the ability to infect germ cells, such as eggs or sperm, which pass their DNA on to future generations. By targeting germ cells, these retroviruses have incorporated themselves into ancestral human genomes over millions of years and may have implications for how researchers screened and tested for disease today.

Active viral genes in the human genome

Viruses insert their genomes into their hosts as a provirus. Today, there are about 30 different types of human endogenous retroviruses in humans, representing more than 60,000 proviruses in the human genome. They demonstrate the long history of the many pandemics to which humanity has been subjected during evolution. Scientists believe that these viruses once infect the population widely because they have taken hold not only in the human genome, but also in chimpanzees, gorillas and other primate genomes.

Research from our lab and others has demonstrated that HERV genes are active in diseased tissues, such as tumors, as well as during human embryonic development. But the activity of HERV genes in healthy tissue was still largely unknown.

To answer this question, our lab decided to focus on a group of HERVs known as HML-2. This group is the most recently active of the HERVs, having disappeared less than 5 million years ago. Even now, some of its proviruses in the human genome retain the ability to make viral proteins.

We examined the genetic material in a database containing more than 14,000 tissue samples from all over the body. We searched for sequences that matched each HML-2 provirus in the genome and found 37 different HML-2 proviruses that were still active. All 54 tissue samples we analyzed showed evidence of activity of one or more of these proviruses. Additionally, each tissue sample also contained genetic material from at least one provirus that could still produce viral proteins.

The role of HERVs in human health and disease

The fact that thousands of pieces of ancient viruses still exist in the human genome and can even create proteins has attracted considerable attention from researchers, especially since related viruses still active today can cause cancer. breast and AIDS-like diseases in animals.

Whether the genetic remnants of human endogenous retroviruses can cause disease in humans is still under investigation. Researchers have spotted HML-2 virus particles in cancer cells, and the presence of HERV genetic material in diseased tissue has been linked to conditions such as Lou Gehrig’s disease, or amyotrophic lateral sclerosis, as well as multiple sclerosis and even schizophrenia.

Our study adds a new angle to these data by showing that HERV genes are present even in healthy tissues. This means that the presence of HERV RNA may not be sufficient to connect the virus to disease.

Importantly, this also means that HERV genes or proteins may no longer be good targets for drugs. HERVs have been explored as a target for a number of potential drugs, including antiretroviral drugs, antibodies for breast cancer, and T-cell therapies for melanoma. Treatments using HERV genes as a cancer biomarker will also need to take into account their activity in healthy tissues.

On the other hand, our research also suggests that HERVs might even benefit people. The most famous HERV integrated into the human and animal genomes, syncytin, 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 virus-derived protein encoded in this gene.

Similarly, mice, cats, and sheep have also found a way to use endogenous retroviruses to protect themselves against the ancient original virus that created them. Although these built-in viral genes are unable to use their host’s machinery to create a complete virus, enough of their damaged pieces are circulating in the body to interfere with the replication cycle of their ancestral virus if the host encounters it. Scientists hypothesize that a HERV may have played this protective role in humans millions of years ago. Our study highlights a few additional HERVs that may have been claimed or co-opted by the human body much more recently for the same purpose.

Unknowns remain

Our research reveals a previously unknown level of HERV activity in the human body, raising as many questions as it answers.

Much remains to be learned about ancient viruses that persist in the human genome, including whether their presence is beneficial and what mechanism drives their activity. It will also be important to see if any of these genes are actually turned into proteins.

Answering these questions could reveal previously unknown functions of these ancient viral genes and better help researchers understand how the human body is responding to evolution alongside these remnants of ancient pandemics.

This article was originally published on The conversation by Aidan Burn at Tufts University. Read the original article here.

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