Ancient viral DNA built into the human genome protects against infections

(ORDO NEWS) — Viral DNA in human genomes, built into humans from ancient infections, serves as antiviral drugs that protect human cells from some modern viruses, according to a new study. The article “Evolution and antiviral activity of a human protein of retroviral origin”.

Previous research has shown that fragments of ancient viral DNA called endogenous retroviruses in the genomes of mice, chickens, cats and sheep confer immunity against modern viruses that originate outside the body by blocking their entry into host cells.

Although this study was done with cultured human cells in a laboratory, it shows that the antiviral effect of endogenous retroviruses probably exists in humans as well.

The study is important because further research may reveal a pool of natural antiviral proteins that allow treatment without autoimmune side effects. The work reveals the possibility of a genome defense system that has not been characterized but may be quite extensive.

“The results show that we have a reservoir of proteins in the human genome that can block a wide range of viruses,” said Cedric Feschott, professor of molecular biology and genetics at the College of Agricultural and Life Sciences, one of the study authors.

Endogenous retroviruses make up about 8% of the human genome – at least four times the amount of DNA that makes up the genes that code for proteins.

Retroviruses inject their RNA into the host cell, which is converted into DNA and integrated into the host genome. The cell then follows the genetic instructions and produces more virus.

Thus, the virus hijacks the cell’s transcription machinery in order to replicate. Typically, retroviruses infect cells that are not passed down from generation to generation, but some of them infect germ cells such as eggs or sperm cells, which opens the door for retroviral DNA to be passed from parent to offspring and eventually become a permanent fixture in the host’s body.

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

In their study, the scientists used computer genomics to scan the human genome and catalog all potential retrovirus envelope protein-coding sequences that could retain receptor-binding activity.

They then ran further tests to determine which of these genes are active, that is, they express products of the retrovirus envelope genes, in specific human cell types.

“We found clear evidence of expression,” Feschott said, “and many of them are expressed in early embryos and germ cells, and some are expressed in immune cells during infection.”

After the researchers identified antiviral envelope proteins expressed in different contexts, they focused on one of them, Suppressyn, because it was known to bind a receptor called ASCT2, the cellular entry point for a diverse group of viruses called type D retroviruses. showed a high level of expression in the placenta and in very early human embryonic development.

They then experimented with cells similar to the human placenta, since the placenta is a common target for viruses.

The cells were exposed to a type D retrovirus called RD114, which is known to naturally infect felines such as the domestic cat. While other human cell types that do not express Suppressyn can be easily infected, placental and fetal stem cells do not.

When researchers experimentally depleted placental Suppressyn cells, they became susceptible to RD114 infection; when Supressin was returned to the cells, they regained resistance.

In addition, the researchers performed reverse experiments using an embryonic kidney cell line normally susceptible to RD114. The cells became resistant when the researchers experimentally injected Suppressyn into these cells.

The study shows how a single human protein of retroviral origin blocks a cellular receptor that allows the virus to enter and become infected by a wide range of retroviruses circulating in many non-human species.

Thus, according to Feschott, ancient retroviruses integrated into the human genome provide a mechanism to protect the developing embryo from infection by related viruses.

According to him, future work will be devoted to the study of the antiviral activity of other envelope proteins encoded in the human genome.

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