Traces of ancient viruses are scattered throughout the human genome, embedded in DNA.
Scientists already know that some of these viral effects can become “active” in cancer cells and possibly contribute to cancer development – but now a new study shows that the virus is also active in dozens of healthy tissues.
“Five or 20 years ago, almost all the endogenous retroviruses in the genome – and there were thousands of them – were largely believed to be in the genome – and there were thousands -” says Matthew Bendal. He is an assistant professor of computational biology research in medicine at Weill Cornell in New York.
In the past six years, scientists have developed more precise ways to study how genes are turned on, Bendal said. But the most recent study focused only on the activity of the old virus in cancerous tumors and a small amount of healthy tissue near these tumors. The new study, published in the journal PLOS Biology, provides greater insight into how active these viral remnants are in the body.
Bendal said, “This study is one of the first insights into what actually happens in normal tissues. We all express some of these residual viruses in all of our tissues, in all of our cells, and I think this study is really important to show that. “
The new research gathered data from the Genotype Tissue and Expression (GTEx) project, a database containing postmortem tissue samples from nearly 950 individuals. These examples include 54 types of disease-free tissue found throughout the body, including the brain, heart, kidneys, lungs, and liver.
To create the database, the researchers analyzed these tissues to see which genes were turned on, as evidenced by the presence of certain strands of RNA in their cells. RNA copies the instructions from patches in the genome and then passes them on to the factories of protein-producing cells so that the factories can pump out the necessary proteins. Some RNA molecules play other roles in the cell, including helping to create these new proteins or “turning genes on and off”.
In the extensive GTEx database, the study authors looked for evidence of “active human retroviruses” (HERVs), aka fragments of ancient viruses woven into the genome. Specifically, they studied a group of HERVs called “HML-2,” which were introduced into the human lineage relatively recently—at least by evolutionary standards. Some of the youngest specimens of HML-2 viruses are hundreds of thousands of years old and are found only in the human genome, and they are not seen in any of our larger relatives, Bendal said.
The authors found evidence of active HML-2 viruses in all 54 disease-free tissue types in the GTEx database, but found the highest level of activation in the cerebellum just behind the brainstem.
What these viruses do to healthy tissue remains a mystery, and the answer is likely different for each tissue type.
“Why is the cerebellum different from the cortex? I think that’s a bit of an open question,” said Bendal. Not surprisingly, he said, some tissues show more variation in HML-2 activation than others.
Bendal notes that when HERVs are turned on, the viral fragments do not give rise to fully functional viruses that can infect cells. Instead, their activation often prompts the cell to create specific RNA molecules, which can stimulate the cell to create proteins. For example, a type of HERV found in primates, including humans, produces a protein needed to form the placenta, according to a 2012 report in the journal Placenta.
Scientists are still working to discover how many of these ancient viruses have affected human biology. The authors of the study wrote that having comprehensive data on what viruses do to healthy tissue provides a basis for comparison with diseased cells.
Bendal added that some scientists have suggested that HERVs could act as potential cancer biomarkers, a measurable signal that clinicians can use to diagnose diseases. In addition, some HERVs, if found to be specific to certain tumor types, could theoretically serve as targets for cancer treatment. But to use HERVs in this way, scientists will need to know how HERVs behave in healthy cells versus cancerous cells.
Source: Life Sciences
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