The following essay is reproduced with permission from 
The Conversation, an online publication covering the latest research.
Remnants of ancient 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% of the human genome, left behind as a result of infections suffered by mankind’s primate ancestors millions of years ago. They became part of the human genome because of how they replicate.
Like modern HIV, these ancient retroviruses had to insert their genetic material into their host’s genome in order to replicate. Usually, this type of viral genetic material is not passed down from generation to generation. But some ancient retroviruses acquired the ability to infect germ cells, such as the egg or sperm, which pass on their DNA to future generations. By targeting germ cells, these retroviruses were incorporated into human ancestral genomes over millions of years and may have implications for how researchers detect and analyze disease today.
Active viral genes in the human genome
Viruses insert their genomes into their hosts as proviruses. There are about 30 different types of human endogenous retroviruses in people today, representing more than 60,000 proviruses in the human genome. They demonstrate the long history of the many pandemics that humanity has been subject to throughout evolution. Scientists believe that these viruses once widely infected the population, as they have become fixed not only in the human genome but also in the genomes of chimpanzees, gorillas and other primates.
Research from our lab 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 recent active HERV, having become extinct less than 5 million years ago. Even now, some of its proviruses within the human genome still retain the ability to produce viral proteins.
We examined the genetic material in a database containing more than 14,000 samples of donated tissue from throughout 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 had some evidence of activity from one or more of these proviruses. Furthermore, 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 fragments of ancient viruses still exist in the human genome and can even create proteins has drawn much attention from researchers, especially since related viruses that are still active today can cause breast cancer and diseases. similar to AIDS in animals.
Whether genetic remnants of human endogenous retroviruses can cause disease in people is still being studied. Researchers have detected HML-2 virus-like particles 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 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. Treatments that use HERV genes as cancer biomarkers will also need to take into account their activity in healthy tissue.
On the other hand, our research also suggests that HERVs might even be beneficial to people. The most famous HERV embedded in 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 also found a way to use endogenous retroviruses to protect themselves against the ancient original virus that created them. While these embedded viral genes cannot use their host’s machinery to create a complete virus, enough damaged pieces circulate in the body to interfere with the replication cycle of their ancestral virus if encountered by the host. Scientists theorize that a HERV may have played this protective role in people millions of years ago. Our study highlights a few more HERVs that could have been reclaimed or co-opted by the human body much more recently for this very 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 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 actually turn into proteins.
Answering these questions could reveal previously unknown functions for these ancient viral genes and help researchers better understand how the human body reacts to evolution alongside these remnants of ancient pandemics.
This article was originally published on The Conversation. Read the original article.
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