As scientists learn more about how the Zika virus can cause brain damage in a developing fetus, a major question has remained: How does a virus that infects a pregnant mother through a mosquito bite on her skin get into her womb?
It is not a simple question. Most viruses that infect a pregnant woman cannot cross from her bloodstream through the placenta, the organ that forms to nourish and protect the fetus as it grows and develops.
But a new study comes the closest so far to explaining how Zika might cross the placenta. The study, published Monday in the journal Cell Host and Microbe, shows that Zika is able to infect several types of placenta cells, and suggests two ways the virus might get to the fetus.
In the lab, researchers tested Zika’s effect on cells from about 50 placentas at different stages of pregnancy. It found that the virus can enter the placenta in every trimester. The risk of the worst damage — babies born with unusually small heads, or microcephaly — appears to be highest in early pregnancy, but significant brain damage might still occur if the mother is infected in late pregnancy, the researchers found.
The study used two strains of the Zika virus — one from Africa and one from the current epidemic in Latin America — and found that the one from Latin America “was much more infectious,” said one of the study’s authors, Lenore Pereira, a virologist and tissue biologist at University of California, San Francisco.
Carolyn B. Coyne, a microbiologist at the University of Pittsburgh, who was not involved in the study, said it was important because it started “drawing a road map” for transmission. “I would say that this is the first study to identify a cell type that could be a primary target during transmission from mom to baby,” she said.
Dr. Coyne is co-author of a recent study showing that the main placental barrier cells, resist Zika by releasing an antiviral molecule. She said the new study appeared to have identified what “could be sort of the Achilles’ heel” in the placenta that allows the virus into the womb.
One possible entry point involves structures called chorionic villi, which anchor the placenta into the wall of the uterus during the first trimester. These anchor points could essentially create openings in the wall, and the researchers found that different types of cells in the villi were easily infected with Zika. This route could be available throughout pregnancy, Dr. Pereira said, but more infected cells appear to produce the virus during the first trimester.
The new research suggests that Zika could also get to the fetus via another route, beginning in the second trimester, crossing the membrane that forms the amniotic sac in which the fetus develops. Cells in that membrane were able to be infected with Zika too, the researchers found.
“The fact that the cells in the amniochorionic membranes, they were pounding out all this virus, we thought, wow, maybe that’s actually a second route,” said Eva Harris, an expert on infectious diseases and vaccines at University of California, Berkeley.
The researchers reported that the Zika virus binds consistently to a protein in different placental cells called TIM1. They also found that a drug, an antibiotic called Duramycin that is currently approved to treat animals but not people, appears to block Zika from attaching to the protein.
That does not mean that Duramycin could be used to treat Zika infection in pregnant women, experts cautioned. Wei Zheng, who runs a lab in the federal Therapeutics for Rare and Neglected Diseases program and is testing drugs as potential Zika treatments, said that Duramycin’s molecules were too large to reach the brain and possibly the fetus. He added that the drug, which is in early clinical trials for cystic fibrosis patients, would need considerably more testing to determine its safety for pregnant women.
Dr. Harris said the study’s authors did not mean to suggest that Duramycin could readily become a Zika treatment. The point, she said, was to show that their experiments provided a model that could be used to test potential drugs that block Zika from entering the womb.
That model might indeed be useful, said Hongjun Song, a neurologist at Johns Hopkins who worked with colleagues at other universities to discover how Zika damages fetal brains. “It provides a hypothesis that now can be directly tested” in animals, said Dr. Song in an email, a way to search for “different routes of viral entry to the fetal brain.”
Dr. Coyne said scientists would likely find other ways that Zika crosses the placenta, perhaps piggybacking on antibodies from a related virus like dengue, which many people in Latin America, especially in Brazil, have previously been infected with. One placental function is transferring helpful antibodies to the fetus, but if Zika attaches to those antibodies, that could be another path to the fetus. “The virus is clearly efficient in getting in,” she said, “so I think that it probably gets in through multiple routes.”