Ancient viral DNA in our genome not ‘junk’ but cancer ally, says study

The study also indicates that targeting and silencing specific endogenous retroviruses could enhance the effectiveness of cancer treatments.

“Our study shows that diseases today can be significantly influenced by these ancient viral infections that until recently very few researchers were paying attention to,” said senior author Edward Chuong, an assistant professor of molecular, cellular, and developmental biology at CU Boulder.

Integral part of human genome

Research indicates that about 8% of the human genome consists of endogenous retroviruses that are integrated into the cells of our evolutionary ancestors, encouraging them to replicate and carry their genetic material.

Over generations, these retroviruses infiltrated sperm, eggs, and embryos, embedding their DNA like a fossil record and influencing evolutionary processes.

Although they can no longer produce functional viruses, Chuong’s research has demonstrated that endogenous retroviruses can function as “switches” to activate nearby genes. Some have played roles in the development of the placenta, a pivotal event in human evolution, and in the immune response to contemporary viruses like COVID-19.

“There’s been a lot of work showing these endogenous retroviruses can be domesticated for our benefit, but not a lot showing how they might hurt us,” Chuong noted.

Viral DNA’s role on cancer growth

To investigate their impact on cancer, Chuong and Atma Ivancevic, a research associate in his lab, examined genomic data from 21 types of human cancers using publicly available datasets.

Their research revealed that a particular lineage of endogenous retrovirus called LTR10, which infected some primates around 30 million years ago, exhibited unexpectedly high activity levels in various cancers, such as lung and colon cancer. Further analysis of tumors from numerous colorectal cancer patients showed that LTR10 was active in about one-third of cases.

Using CRISPR to remove or silence sequences where LTR10 was present, the team found that critical genes promoting cancer development and growth were also deactivated.

“We saw that when you silence this retrovirus in cancer cells, it turns off nearby gene expression,” Ivancevic explained.

“We know that cancer cells express a lot of genes that are not supposed to be on, but no one really knows what is turning them on,” Chuong said. “It turns out many of the switches turning them on are derived from these ancient viruses.”

Other health issues

Interestingly, the endogenous retrovirus examined in their study appears to activate genes within the MAP-kinase pathway, a well-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 deactivating the endogenous retrovirus switch.

According to the authors, this single retrovirus family regulates up to 70 cancer-associated genes in the MAP-kinase pathway. Different retrovirus lineages likely affect various pathways, promoting different types of cancers.

Chuong theorizes that as individuals age, their genomic defenses deteriorate, allowing ancient viruses to reactivate and potentially contribute to other health issues as well.

This study was published in Science Advances.