Embedded within the approximately 20,000 genes that make up the human genome are fragments of viral DNA, remnants of viral infections that infected primate ancestors millions of years ago. These ancient pieces of DNA, called endogenous retroviruses, were once thought to be harmless and inactive.

However, a recent study by researchers from the University of Colorado reveals that they retroviruses can reactivate and play a vital role in cancer development and survival. The study also suggests that targeting and silencing specific endogenous retroviruses could enhance the effectiveness of cancer treatments.

“Our study shows that diseases can be significantly influenced by these ancient viral infections that, until recently, very few researchers paid attention to,” said lead author Edward Cwong, assistant professor of molecular, cellular and developmental biology at the University of Colorado.

Research shows that about 8% of the human genome consists of endogenous retroviruses that carry their genetic material. These retroviruses have penetrated sperm, eggs and embryos and affected evolutionary processes.

Although they can no longer produce functional viruses, the new study showed that endogenous retroviruses act like “switches” that turn genes on. Some have played a role in the development of the placenta, a pivotal event in human evolution, and in the immune response to modern viruses such as COVID-19.

The role of viral DNA in cancer development

To investigate the effect of these viruses on cancer, the researchers examined genomic data from 21 types of cancer. Their research revealed that a particular line of endogenous retroviruses called LTR10, which infected some primates about 30 million years ago, showed unexpectedly high levels of activity in various cancers, such as lung and colon cancer. Further analysis of tumors from colon cancer patients showed that LTR10 retroviruses were active in about 1/3 of the cases.

Using CRISPR gene-editing technology to remove or silence sequences where the LTR10 retroviruses were located, the team found that critical genes that promote cancer growth were also turned off.

“We found that when we silenced this retrovirus in cancer cells, gene expression was turned off,” they explained.

“We know that cancer cells express many genes that shouldn’t be turned on, but no one really knows what turns them on,” said Chuang. “It turns out that many of the switches that turn them on come from these ancient viruses,” he added.

Other health issues

The endogenous retrovirus the researchers tested appears to activate genes in the MAP-kinase pathway, a known cellular pathway that is often dysregulated in many cancers. The study suggests that existing drugs called MAP-kinase inhibitors may work, in part, by turning off the endogenous retrovirus switch.

According to the study authors, this family of retroviruses regulates up to 70 cancer-related genes in the MAP-kinase pathway. Different lineages of retroviruses likely affect different pathways, promoting different types of cancer. Chuong believes that as people age, their genomic defenses decline, allowing ancient viruses to reactivate and potentially contribute to other health problems.

The study was published in the scientific journal Science Advances.