Researchers at Baylor College of Medicine discovered that the trophoblast cells of the placenta may serve as a potential reservoir, or portal, of fetal transmission of the virus. The trophoblasts are a self–renewing population of cells that support the developing fetus.

The findings, appeared in the journal Scientific Reports, lend hope to the possibility that in the future care providers could use existing prenatal diagnostic techniques to detect the virus in the placental cells and someday find a way to stop its spread to the fetus.

The research team isolated the virus from a patient who had been infected during the current epidemic in Colombia and propagated the Zika virus once. Next, they collected placental samples from 20 uninfected donors in Houston who had delivered uninfected and non–exposed infants at or near term. They isolated the trophoblasts from the placental samples to create a pure population of trophoblasts that they incubated for just one hour with the Zika virus. They then looked up to eight days later for ongoing replication of the virus, as well as changes in the placental trophoblast cells themselves.

“We found that the virus can replicate in trophoblasts from every donor tested, and it does not kill the trophoblasts but instead allows them to continue doing their day to day function, including production of the pregnancy hormone bhCG,” said Dr. Melissa Suter, assistant professor of obstetrics and gynecology at Baylor and a co–author on the study.

Researchers used three techniques to show that Zika virus, but not its related cousin dengue virus, was capable of propagating in placental trophoblast cells. First, they used a double stranded antibody that is not specific to Zika virus but is common to several related viruses and showed that the replicating virus was present in the pure population of trophoblasts.

Next, they specifically measured Zika virus nucleic acid using the polymerase chain reaction (PCR) test, which is equivalent to the clinical test used for Zika virus. They observed an increase in message level by PCR.

Finally, they generated a series of fluorescent probes against single molecules of RNA and hybridized both RNA strands to visualize the replication of the virus at a single molecule level in these pure trophoblast population from uninfected donors.

Researchers also wanted to determine how the Zika virus might enter the trophoblast cells and why the virus replicates in the placental trophoblasts when other viruses do not.

To answer this, they first looked at transcribed message of several putative cell entry receptors for Zika virus, and found that these important receptors are made in uninfected placental trophoblast cells. They also looked at the localization of expression of one such entry receptor, AXL, and found it on the cell surface of the trophoblast.

The researchers then looked in both infected and uninfected trophoblast primary cultures for the expression of microRNA’s and found that some were changed in their expression unique to Zika. Specifically, they looked at miR21, a ligand–binding microRNA receptor that binds to Toll–like receptors 7 and 8 and found that the presence of Zika virus infection caused a decrease in the amount of miR21.

“It’s interesting because it’s a Toll–like receptor binding ligand, and that may be one of the ways that Zika virus can dampen an otherwise active immune response that would be functioning to keep the virus at bay,” said Dr. Max Seferovic, a postdoctoral associate in obstetrics and gynecology at Baylor and co–author on the study.

“In the older African Zika strain, we have not seen an association with fetal brain malformations or microcephaly,” Aagaard said.