DNA from viruses that have inserted themselves into the human genome activate in the early stages of embryonic development, a new paper in Nature reports, and help protect us from other infections while determining which genes are expressed.
Stanford University's Dr. Joanna Wysocka found that viral proteins are produced in such quantities by some of the first cells that appear in a human embryo that the cells can become crowded with these particles.
“It’s both fascinating and a little creepy,” Wysocka said.
Retroviruses, most famously HIV and Hepatitis B, infect our cells and insert themselves into our DNA, where they hide from the immune system to be reactivated later.
Each time a cell divides, the virus is replicated along with the genetic material in which it is hiding. Clever as this is, the really smart evolutionary move is to become an endogenous retrovirus and infect a germ cell that becomes either sperm or egg. In this case, the virus is passed on to future generations. One way to do this is to infect early-stage embryo cells before they have differentiated so that some become germ cells.
However, like any parasite, viruses that kill their host are at an evolutionary disadvantage, and this particularly applies to those that impose a cost on embryonic cells they have infected – growing into a full human being is hard enough without carrying a burdensome virus. Some retroviruses, however, manage to be fairly harmless and therefore get passed on from generation to generation, losing the ability to spread other than by the reproduction of their host. These inactivated viruses can be recognized by distinctive DNA segments and make up about 8% of the human genome.
Even when a retrovirus is normally inactivated, however, special circumstances can stimulate a revival. This has been known to happen in cancer cells, but in February, a Cell Stem Cell paper demonstrated that the HERVK retrovirus—the most recent arrival in our genome—activates in the early stages of embryonic development.
Wysocka has demonstrated that this is not an isolated occurrence, but rather an example of an abundance of viral proteins produced after the point when there are just eight cells. Moreover, she has shown that these proteins appear to help ward off infection by other viruses by increasing the protein IFITM1 on the surface of cells, and may influence which of our genes are expressed.
What Wysocka has not yet worked out is whether these viruses represent a benefit to us overall; in other words, are they symbiotic allies or parasites we barely keep under control?
It may be that it is our viruses that make us human. “Our early human development is unique and depends on genes and DNA sequences we picked up recently in our evolutionary history,” says co-author Professor Renee Reijo Pera of Montana State University. There are hints these are triggered by HERVK.
“The mere observation that viral proteins are expressed and able to engage cellular machinery in complex ways shows that in order to fully comprehend intricacies of early human development, we need to consider the function of these genome invaders,” Wysocka said.