Do captured viral genes make human pregnancies possible?

Science News, May 13, 2000 by John Travis

The bond between a mom and her newborn is strong, but it doesn't compare to the connection formed during pregnancy. Soon after conception, the fetus literally invades the woman's uterine wall, acting like a parasite that steals nutrients and oxygen from its host.

The placenta, a tissue created by the developing embryo while it's still a ball of cells, mediates this intrusion. As the physical interface between mother and child, a placenta helps prevent the maternal immune system from rejecting the baby as foreign tissue. Early in pregnancy, it also secretes hormones that prepare the uterine lining to receive the fetus. Then, placental cells burrow into the uterus, where they burst maternal blood vessels to create pools of blood from which a fetus draws sustenance and into which it deposits wastes. Later, placental hormones ready the fetus for delivery.

"In many ways, the placenta is the SCUBA system for the fetus, while at the same time being the Houston Control Center guiding the mother through pregnancy," reproductive biologist Harvey J. Kliman of Yale University School of Medicine in New Haven, Conn., notes.

Despite the tissue's sophistication, evolution created the placenta only within the past 100 million years. Earlier, all animals laid eggs, which forced offspring to develop quickly and independently of their mothers. Biologists view placental pregnancy as a major advance because it allows a mother to nourish and protect an embryo longer.

"We know that the longer the gestation, the greater potential there is for fetal neurological development," notes placental biologist James C. Keith of the biotech firm Genetics Institute in Cambridge, Mass.

As with many evolutionary adaptations, the origins of the placenta remain shrouded in mystery. That hasn't kept biologists from speculating, however. One remarkable conjecture concerns viral genes that became embedded in the genomes of the forerunners of mammals. These captive genes, the theory holds, may have facilitated the placenta's evolution.

This provocative scenario recently got its first solid dose of supporting data. At least two viral genes captured by the human genome millions of years ago encode proteins that, according to new experiments, may guide the development of the human placenta. The data on one of the proteins remain controversial, but work with the other protein strongly suggests that it fuses placental cells. This finding may explain the creation of the unusual but crucial barrier linking the blood supplies of mother and fetus.

Beyond shedding light on placental evolution, these viral genes could provide insight into pregnancies that go awry. Investigators are already examining whether the genes are defective in women who have had problem pregnancies.

The story of the placenta and its viruses begins with some suspicious black-and-white photos. In the 1970s, investigators focused powerful electron microscopes on placental tissue from mice, cats, baboons, and people. The resulting images unexpectedly revealed viruslike particles budding from apparently healthy cells.

The particles turned out to be retroviruses, a viral family that includes the AIDS virus. Like other viruses, retroviruses must sneak their genetic material into cells and command a cell's internal machinery to replicate themselves. Unlike their viral relatives, retroviruses have adopted a strategy for permanently inserting a copy of their genes into the genomes of the cells they invade.

Throughout the 1970s and 1980s, notes Erik Larsson of the Uppsala University in Sweden, investigators continued to gather evidence that the placenta is a hot spot for retroviral activity. They also began to theorize about why. Larsson and other biologists saw a few obvious possibilities.

As the AIDS virus so tragically confirms, most retroviruses have a knack for suppressing a host's immune system. Consequently, the fetus may use retroviral proteins to help prevent the mother from rejecting it as foreign. After all, half the fetus' genes come from the father.

"You just need to express [the retroviral genes] for a rather short time because the placenta produces several strong immunosuppressive proteins that are not related to retroviruses," says Larsson.

Another theory drew upon the unusual anatomy of the placenta. As it invades the uterine wall, this tissue develops fingerlike projections that penetrate pools of maternal blood. These fingers extend from a single thin cell, called the syncytiotrophoblast or the placental syncytium, which contains multiple nuclei.

Such merged cells are rare in the human body, and scientists have wondered whether proteins from retroviruses create this cell layer. Viral surface molecules known as envelope proteins fuse certain viruses to a cell as the first step in infecting it. The AIDS virus, HIV, even appears to use its envelope proteins to fuse immune cells to each other (SN: 12/19&26/98, p. 391).

It's hard to imagine that women get infected with a retrovirus every time they become pregnant. Where else could the placental retroviral components come from? From within. Surprisingly large portions of mammalian genomes, perhaps as much as 1 percent in people, consist of so-called endogenous retroviruses.