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

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

HERVs, or human endogenous retroviruses, make up about 8 percent of the human genome, left behind as a result of infections suffered by humanity’s primate ancestors millions of years ago. They became part of the human genome because of the way they reproduce.

Like modern HIV, these ancient retroviruses had to insert their genetic material into their host’s genome in order to reproduce. Usually, this type of viral genetic material is not passed from generation to generation. However, some ancient retroviruses acquired the ability to infect germ cells, such as eggs or sperm, which pass their DNA to future generations. By targeting germ cells, these retroviruses became integrated into human ancestral genomes over millions of years and may have implications for the way researchers examine and test for disease today.

Active viral genes in the human genome

Viruses introduce their genomes into their hosts in the form of a provirus. There are approximately 30 different species of human endogenous retroviruses in humans today, amounting to over 60,000 proviruses in the human genome. They demonstrate the long history of the many pandemics humanity has been subjected to during evolution. Scientists believe that these viruses once widely infected the population, having stabilized not only in the human genome but also in the genomes of chimpanzees, gorillas and other primates.

Research from our laboratory and others has shown that HERV genes are active in diseased tissues, such as tumors, as well as during human embryonic development. But how active HERV genes are 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 gone extinct less than 5 million years ago. Even now, some of its proviruses in the human genome still retain the ability to produce viral proteins.

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

The role of HERVs in human health and disease

The fact that thousands of pieces of ancient viruses are still present in the human genome and can even make proteins has caught the attention of researchers, particularly because related viruses that are still active today can cause breast cancer and breast-like diseases. AIDS in animals.

Whether genetic remnants of human endogenous retroviruses can cause disease in humans is still under study. Researchers have detected virus-like particles from HML-2 in cancer cells, and the presence of HERV genetic material in diseased tissue has been associated with 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 tissue. This means that the presence of HERV RNA may not be enough to link the virus to a disease.

Importantly, it also means that HERV genes or proteins may no longer be good drug targets. 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. Therapies using HERV genes as a cancer biomarker should also consider their activity in healthy tissue.

On the other hand, our research also shows that HERVs could be beneficial even for humans. The most famous HERV integrated into human and animal genomes, syncytin, is a gene derived from an ancient retrovirus that plays an important role in placental formation. 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 from the original ancient virus that created them. While these integrated viral genes are unable to use their host’s machinery to make a complete virus, enough of their damaged pieces circulate in the body to interfere with the replication cycle of their progenitor virus if the host encounters it. Scientists think that a HERV may have played this protective role in humans millions of years ago. Our study highlights a few more HERVs that could have been claimed or co-opted by the human body much more recently for the same purpose.

They remain unknown

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

There is still much to learn about the ancient viruses that remain 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 translated into proteins.

Answering these questions could reveal previously unknown functions of these ancient viral genes and help researchers better understand how the human body responds 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.

Leave a Reply

Your email address will not be published. Required fields are marked *