Ancient viruses activate in healthy cells of the human body

(ORDO NEWS) — Traces of ancient viruses are scattered throughout the human genome, embedded in the structure of DNA.

Scientists already knew that some of these viral artifacts could “activate” in cancer cells and potentially contribute to the progression of the disease, but now a new study shows that the viruses are active in dozens of healthy tissues as well.

“15 or 20 years ago, it was believed that almost all of these endogenous retroviruses that are in the genome, and there are thousands of them, are silent in normal tissues,” said Matthew Bendall, assistant professor of computer-aided biological research in medicine at Weill Cornell Medicine in New York.

“They’ve been relegated to this category of ‘junk DNA’, parts of our genome that don’t have any function.”

This assumption has been challenged in the past six years or so as scientists have developed more sensitive methods to study gene activation.

But the most recent research has focused only on the activation of the ancient virus in cancerous tumors and in the small amount of healthy tissue next to these tumors.

A new study published recently in the journal PLOS Biology provides a broader picture of just how active these virus residues are in the body.

“This study is really one of the first looks at what happens in normal tissues,” said Bendall.

“We all express in all of our tissues, in all of our cells, some of these viral residues, and I think this study is really important to show that.”

The new study drew on data from the Genotype Tissue and Expression (GTEx) project, a database that includes tissue samples taken after death from nearly 950 people.

These samples include 54 types of healthy tissue found throughout the body, including the brain, heart, kidneys, lungs and liver.

To create a database, the researchers analyzed these tissues to see which of their genes were “turned on”, as evidenced by the presence of specific strands of RNA in their cells.

RNA, a molecular relative of DNA, copies the instructions from sections of the genome and then relays them to a kind of protein factory in the cells so that they can pump out the necessary proteins.

Some RNA molecules perform other functions in the cell, including helping to build these new proteins or turning genes on and off.

In the vast GTEx database, the study authors searched for evidence of the existence of active “human endogenous retroviruses” (HERVs), that is, pieces of ancient viruses woven into the genome.

In particular, they tested a group of HERVs called “HML-2,” which was introduced into the human lineage relatively recently – at least by evolutionary standards.

Yet some of the youngest examples of HML-2 viruses are only a few hundred thousand years old and are only found in the human genome, meaning they are not found in any of our primate relatives.

The authors found evidence in the GTEx database for active HML-2 viruses in all 54 healthy tissue types, but the highest levels of activation were found in the cerebellum, located just behind the brainstem.

What these viruses do in healthy tissue is still a mystery, and the answer is probably different for each type of tissue.

“Why is the cerebellum different from the cortex? I think it’s an open question,” Bendall said.

But not surprisingly, some tissues showed a greater degree and variety of HML-2 activation than others, he explained.

Bendall noted that when HERV is incorporated, viral fragments do not produce whole, functional viruses capable of infecting cells.

Rather, their activation usually induces the cell to build specific RNA molecules, which can then induce the cell to build proteins.

For example, one type of HERV, present in primates, including humans, produces a protein that is key to building the placenta.

Scientists are still working to figure out how most of these ancient viruses affect human biology. The authors of the study wrote that having comprehensive data on what viruses do in healthy tissues provides a basis for comparison with diseased cells.

Some scientists have suggested that HERVs could act as potential cancer biomarkers, meaning a measurable signal that doctors can use to screen for disease.

In addition, some HERVs could theoretically serve as targets for cancer treatment if found to be unique to certain types of tumors.

But to use HERVs in this way, scientists need to know how HERVs behave in healthy cells compared to cancer cells.

Future work should look at endogenous families of retroviruses beyond HML-2, Bendall said. This is important work, because dozens of types of ancient viruses lurk in our genomes, which are still waiting to be explored.


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