A virus that emerged 500 million years ago now plays a key role in embryo formation.

The evolution of man on the planet is associated with Virus and bacteria. Sometimes with more luck than others. We live with them, they are part of us. What trace did those who inhabited the Earth millions of years ago leave for us? Recent research has revealed the key role of an endogenous retrovirus in embryo formation.

The working group of the National Cancer Research Center (CNIO) is responsible for this discovery. The study in which it is published Science achievementsshows that A virus that infected animals millions of years ago is now key to the development of human life.

Research that is now seeing the light of day highlights the role of the endogenous retrovirus MERVL setting the pace of embryonic development, especially at a certain stage of the transition from totipotency to pluripotency, and explains the mechanism by which this occurs. This is exactly what happens a few hours after fertilization: the transition to pluripotency, when the oocyte has two to four cells.

This comes from the cell’s ability to create a complete organism, totipotency, to the cell’s ability to create various types of tissues and organs. Hence the importance know what happens at these key moments to meet needs in the area of regenerative medicine and in the creation of artificial embryos. This achievement opens up new possibilities in the creation of stable cell lines in the totipotency phase.

So far, the discovery has been made in mouse models. “This is a completely new role for endogenous retroviruses,” he says. Nabil Juder, senior author of the paper and leader of the CNIO’s Growth Factors, Nutrients and Cancer Group, the statement said. “We have discovered a new mechanism that explains how an endogenous retrovirus directly controls pluripotency factors.“.

Together with Juder Sergio de la Rosa He is the first to sign the publication. This researcher was looking for an answer to the question of why, when the URI gene is deleted in laboratory animals, embryos do not even develop. Juder’s group is thoroughly researching the role of URIs. In humans, this protein is part of a process whose function is to help other proteins fold correctly. After finding the answer, De la Rosa discovered its connection to an endogenous retrovirus called MERVL.

“Our conclusions reveal the symbiotic coevolution of endogenous retroviruses with host cells, to ensure smooth and timely progression of early embryonic development,” the authors write in the publication.

In other words, the tripartite relationship between the viral protein, URI, and pluripotency factors is very finely modulated “to give the embryo sufficient time to adapt and coordinate a smooth transition from totipotency to pluripotency, as well as cell lineage specification.” during embryonic development,” Juder emphasizes.

How does the virus come to play a role in embryonic development?

The genetic material of so-called endogenous retroviruses was integrated into the genome of creatures that may be the protagonists of the Cambrian explosion, which occurred more than 500 million years ago, when the planet’s seas experienced a boom in biodiversity. Over the past decade, it has been discovered that genetic sequences These viruses make up at least 8-10% of the human genome..

“Until very recently These viral remains were considered “junk DNA.” useless or even harmful genetic material,” explains De la Rosa. “Intuitively, it was believed that the presence of viruses in the genome could not be good. But in recent years, we are realizing that these retroviruses, which have evolved with us over millions of years, perform important functions, such as regulating other genes. “This is a very active area of ​​research.”

Three-way communication: MERVL virus, URI gene and pluripotency.

The results of the CNIO study indicate that one of the functions of URI is to mediate the action of essential molecules to acquire pluripotency; If the URI does not act, then the pluripotency factors do not act, and the cell remains in a state of totipotency. Thus it turns out that is a protein of the endogenous retrovirus MERVL-gag, which, in turn, modulates the action of URI..

Scientists have discovered that during the totipotency phase, when there are only two cells in the oocyte, the expression of the viral protein MERVL-gag he is tall; This protein binds to the URI and prevents its action. But gradually the levels change, so that the level of the viral MERVL-gag protein falls and the URI can take effect: pluripotency appears.

As De la Rosa explains, it is “a smooth transition: when you have high viral protein expression, you have fewer pluripotency factors; when the expression of endogenous retroviruses (ERVs) is reduced, you allow URI to stabilize these factors.”

In conclusions paperthe authors state that “a burst of endogenous retrovirus transcription during zygotic genome activation may control the stability of the pluripotency factor to give the embryo sufficient time to adapt and coordinate the smooth transition from totipotency to pluripotency and cell lineage specification during embryonic development. ERV activation may represent additional heterogeneous power bias source during development in the blastomere, playing a key role in cell lineage segregation in the early embryo.”

Therefore they emphasize that “ERVs have evolved in symbiosis with host cells. to precisely modulate transitions of cellular activity and ensure timely progression and specification of cell lineages during the early stages of embryonic development.”