Traces of ancient viruses are scattered throughout the human genome, embedded in DNA.
Scientists already knew that some of these viral effects could be “active” in cancer cells and possibly promote cancer, but now a new study has shown that the viruses are active in dozens of healthy tissues as well.
“Five or 20 years ago it was widely believed that almost all of the endogenous retroviruses in the genome — and there are thousands of them — were mostly thought to be in genomes — and there are thousands of them —,” said Matthew Bendahl, assistant professor of computer-aided biological research in medicine at Weill Cornell. , New York, which was not included in the study. Most of it is silenced in normal tissues.”
Over the past six years or so, scientists have developed more sensitive ways to study how genes turn on, Bendal says. But the most recent research has focused only on the activity of the old virus in cancerous tumors and in a small amount of healthy tissue near these tumors. New study published in the journal PLOS Biologya bigger picture of how active these viral remnants are throughout the body.
“This study is really one of the first insights into what happens in normal tissues,” said Bendal. “We all express in all of our tissues, in all of our cells, some of these viral residues, and I think this study is important.” “. it’s really important to show it.”
The new study pulled data from the Genotype Tissue and Expression (GTEx) project, a database that includes post-mortem tissue samples 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 indicated by the presence of certain strands of RNA in their cells. RNA copies the instructions from sections of the genome and then passes them on to the cell’s protein factories so that the factories can pump out the proteins they need. Some RNA molecules play other roles in the cell, including helping 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 retroviruses” (HERVs), that is, parts of ancient viruses woven into the genome. In particular, they examined a group of HERVs called “HML-2” that were introduced into the human lineage relatively recently – at least by evolutionary standards. Bendal said some of the youngest examples of HML-2 viruses are hundreds of thousands of years old and only found in the human genome, meaning they didn’t appear in any of our main relatives.
The authors found evidence for the presence of active HML-2 viruses in all 54 healthy tissue types in the GTEx database, but found the highest levels of activation in the cerebellum just behind the brainstem.
What these viruses do in healthy tissue remains a mystery, and the answer is likely to be different for each type of tissue.
“Why is the cerebellum different from the cortex? I think it’s an open question,” Bendal said. Not surprisingly, he said, some tissues show a greater degree of diversity in HML-2 activation than others.
Bendahl noted that when HERV is incorporated, viral fragments do not produce fully functional viruses capable of infecting cells. Instead, their activation usually prompts the cell to build specific RNA molecules, which can then stimulate the cell to build proteins. For example, according to a 2012 report in the journal Placenta, one type of HERV found in primates, including humans, produces a protein needed to build the placenta.
Scientists are still working to figure out how most of these ancient viruses affected 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.
Bendal added that some scientists have suggested that HERVs could act as potential cancer biomarkers, meaning a measurable signal that clinicians 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.
Source: Living Science