This article was published today in Science magazine
.
About 30 million years ago, a virus infected our primate ancestors, and one of the genes was trapped in
their genome.
Over time, this viral gene becomes "domesticated" and regionalized
.
It helps primates defend against other viruses, preventing them from entering cells
.
The invader, known as Suppressyn (SUPYN), still exists today, and it's still helping us out of it: A new study suggests that this viral shell may help the placenta protect embryos from viral infections
.
Giulia Pasquesi, an evolutionary biologist at the University of Colorado Boulder, said: "It's a good story and very strongly supported by experiments
.
Finding more of these viral genes may help us harness or enhance our inherent antiviral properties without developing new drugs or vaccines
.
We already have all these elements
in our genome.
”
Viruses that embed genetic material in our genomes are called retroviruses
.
HIV is probably the most famous example; Once integrated into our genes, it hijacks our body's cellular machinery to produce more viruses
.
If they infect sperm or oocytes, the precursors of eggs, their genes become part of our DNA and can be passed on to our offspring
.
Once a viral DNA fragment is embedded in our genome, it is called an endogenous retrovirus (ERV).
About 8% of the human genome is made up of ERV sequences that have been in our DNA since infecting our ancestors millions of years ago
.
Over time, these genes have lost their original viral function, but that doesn't mean they're
useless.
To find out which ERVs might still be active in humans, Cedric Feschotte, a molecular biologist at Cornell University, and his colleagues scanned the human genome for ERV sequences
they suspected might encode proteins.
They found 1507 such sequences, about half of which appear to work
in human tissue.
An ERV produces a protein in an early human placenta called Suppressyn (SUPYN).
SUPYN binds to a receptor on the cell surface called ASCT2, another protein from ERV, Syncytin, used to form connections between cells
.
Previously as a retrovirus, syncytial proteins can fuse with cell membranes into cells; Its modern form allows the placenta to form
through fusion cells during fetal development.
Without it, the evolution of the placenta could not have happened
.
Welkin Johnson, a virologist at Boston College, said: "You could say that without retroviruses, there would be no mammals
.
It's as if life wouldn't evolve
as it does now.
”
But ASCT2 is also the Achilles heel
of mammals.
Viruses known as type D retroviruses use it to bypass cellular defense systems and sneak into cells, causing a variety of diseases in many animals, including nonhuman primates
.
However, it is not known to infect humans
.
Feschotte says that if early animals don't have a way to protect themselves from these retroviruses, this could pose a major challenge
for them.
Protecting the placenta is especially important because retroviruses infected early in embryonic development can enter sperm and egg cells
.
When Feschotte and his colleagues experimentally infected human placental cells with a retrovirus virus, they found that SUPYN prevented the virus from entering the cell
by blocking ASCT2 receptors from competing with pathogens.
WHEN THESE CELLS DETECTED THE VIRUS, THEY APPEARED TO ACTIVATE SUPYN, WHICH SUGGESTS IT ENCODES AN ANTIVIRAL PROTEIN
.
Johnson noted that it's not clear whether SUPYN actually blocks any virus in humans: Although type D retroviruses can infect macaques and other primates, none appear to infect humans
.
"There are already means and motives; The problem is opportunity," he said
.
"It's all the guilt of association
.
"
Still, Johnson praised the article
.
HE NOTED THAT IT'S POSSIBLE THAT SUPYN EVOLVED TO STOP AN ALREADY EXTINCT VIRUS, OR MAYBE IT DID SUCH A JOB SO WELL THAT IT BLOCKED THE ENEMY VIRUS FROM GAINING A FOOTHOLD
.
Pasquesi added that it was technically impressive that the authors managed to find out which receptor these retroviruses used to enter the
cells.
She is currently conducting a similar study mapping domesticated cerebral blood vessels in the human genome and has identified about 30 viruses
that are important for the human immune system.
"It's
amazing that our own bodies can make so many antiviral drugs," she said.
”
The team now plans to study dozens of other active retroviruses
they identified.
He noted that although SUPYN is thought to be a functional human gene, 99 percent of the other active ERVs they found looked like unimportant junk DNA but could seem like
a lie.
"It's a treasure trove of potential proteins that have at least the potential to have interesting activities
in medicine, physiology or development.
"
