Ancient viral DNA in human genome guards against infections

Viral DNA in human genomes, embedded there from ancient infections, serve as antivirals that protect human cells against certain present-day viruses, according to new research

Previous studies have shown that fragments of ancient viral DNA “called endogenous retroviruses” in the genomes of mice, chickens, cats and sheep provide immunity against modern viruses that originate outside the body by blocking them from entering host cells. Though this study was conducted with human cells in culture in the lab, it shows that the antiviral effect of endogenous retroviruses likely also exists for humans

The research is important because further inquiry could uncover a pool of natural antiviral proteins that lead to treatments without autoimmune side effects. The work reveals the possibility of a genome defense system that has not been characterized, but could be quite extensive

“The results show that in the human genome, we have a reservoir of proteins that have the potential to block a broad range of viruses,” said Cedric Feschotte, professor of molecular biology and genetics in the College of Agriculture and Life Sciences

Endogenous retroviruses account for about 8% of the human genome -at least four times the amount of DNA that make up the genes that code for proteins. Retroviruses introduce their RNA into a host cell, which is converted to DNA and integrated into the host’s genome. The cell then follows the genetic instructions and makes more virus

In this way, the virus hijacks the cell’s transcriptional machinery to replicate itself. Typically, retroviruses infect cells that don’t pass from one generation to the next, but some infect germ cells, such as an egg or sperm, which opens the door for retroviral DNA to pass from parent to offspring and eventually become permanent fixtures in the host genome

In order for retroviruses to enter a cell, a viral envelope protein binds to a receptor on the cell’s surface, much like a key into a lock. The envelope is also known as a spike protein for certain viruses, such as SARS-CoV-2

In the study, Frank, Feschotte and colleagues used computational genomics to scan the human genome and catalog all the potential retroviral envelope protein-coding sequences that may have retained receptor binding activity. Then they ran more tests to detect which of these genes were active — that is, expressing retroviral envelope gene products in specific human cell types

“We found clear evidence of expression,” Feschotte said, “and many of them are expressed in the early embryo and in germ cells, and a subset are expressed in immune cells upon infection”

Reference: https://www.biorxiv.org