An international research team reported this week that the Zika virus is transmitted from mother to her fetus by infected cells that will later develop into the brain's first and primary form of defense against invasive pathogens.
The discovery, detailed in a study published in the current online issue of Human Molecular Genetics, may open a pathway for a potential treatment for infected patients.
"It's a Trojan Horse strategy," Alysson Muotri, a professor at the University of California San Diego School of Medicine, was quoted as saying in a news release.
She said that during embryogenesis, the early stages of prenatal development, cells called microglia form in the yolk sac and then disperse throughout the central nervous system (CNS) of the developing child. In the brain, these microglia constantly clears away plaques, damaged cells and infectious agents.
The new findings show that "the Zika virus can infect the early microglia, sneaking into the brain where they transmit the virus to other brain cells, resulting in the devastating neurological damage we see in some newborns," Muotri said.
Beginning in 2015, a dramatic increase in children born with microcephaly, a condition in which their heads are smaller than normal, and other birth defects were observed in Brazil. The phenomenon was subsequently linked to infection by the Zika virus, which Muotri and others confirmed last year caused birth defects in experimental models.
The Zika virus is spread from Aedes species mosquitoes to humans in tropical regions, but the method of transmission from a pregnant mother to her unborn child, though scientists have not been able to precisely describe the mode of transmission.
"Considering the timing of transmission, we hypothesized that microglia might be serving as a Trojan horse to transport the virus during invasion of the CNS," said Muotri.
To test their hypothesis, researchers at the University of California San Diego School of Medicine, with colleagues in Brazil used human induced pluripotent stem cells to create two relevant CNS cell types: microglia and neural progenitor cells (NPCs), which generate the millions of neurons and glial cells required during embryonic development. Then they established a co-culture system that mimicked the interactions of the two cell types in vitro when exposed to the Zika virus.
According to the new study, the microglia cells engulfed Zika-infected NPCs, doing their job. But when these microglia carrying the virus were placed in contact with non-infected NPCs, they transmitted the virus to the latter.
The scientists also tested a drug called Sofosbuvir, marketed as Sovaldi and used to treat hepatitis C, and found it "significantly decreased cell death of NPCs and the viral load in NPCs".
Muotri said they were encouraging, suggesting microglial cells could be a therapeutic target for reducing Zika transmission into the CNS of developing fetuses.
Though the findings are based on in vitro research, more investigation is needed.
