By now it is well known that infection by the mosquito-spread Zika virus can cause devastating birth defects. Most notably, affected infants can have abnormally small skulls and underdeveloped brains. Scientists have been scrambling to find out why.
Now infectious disease expert Catherine Blish, MD, PhD and developmental biologist Joanna Wysocka, PhD, along with graduate students Nicholas Bayless and Rachel Greenberg, have found that a population of cells called cranial neural crest cells can — at least in the laboratory — also be infected by Zika. They published their results today in Cell Host & Microbe.
From our release:
Cranial neural crest cells are cells that arise in humans within about five to six weeks of conception. Although they first appear along what eventually becomes the spinal cord, the neural crest cells migrate over time to affect facial morphology and differentiate into bone, cartilage and connective tissue of the head and face. They also provide critical molecular signals that support nearby developing neurons in the brain.
Because Zika-affected babies also sometimes have facial abnormalities, Bayless and Greenberg wondered whether cranial neural crest cells could be infected by the Zika virus.
From our release:
Recent research has focused on the effect of Zika virus infection of the neural precursor cells that give rise to neurons in the developing brain. But Bayless and Greenberg found that not only can cranial neural crest cells also be infected by the Zika virus, they respond differently than their neighboring neural precursor cells to the infection. Rather than rapidly dying, as the neural precursors do, the cranial neural crest cells act as a reservoir for the virus by allowing it to replicate repeatedly. In addition, they begin to secrete high levels of cytokines, including leukemia inhibitory factor and vascular endothelial growth factor, known to affect neural development.
When Bayless and Greenberg exposed neural precursor cells to levels of cytokines equivalent to what was secreted by the infected cranial neural crest cells, the neural precursor cells displayed an increase in structures associated with cellular migration and growth. The cells also began to initiate a program of cellular suicide.
The researchers emphasize that their results were obtained only on cells grown in the laboratory and haven't been confirmed in humans. But the findings may provide another way of thinking about how brain size is curtailed by Zika infection.
As Wysocka explained:
Our study brings attention to the possibility that other infected embryonic cell types in the developing head can influence Zika-associated birth defects, including microcephaly, perhaps through signaling to neighboring cells or by serving as a viral replication reservoir.
Previously: Zika is just one of many tropical viruses headed our way, says Stanford expert, Countdown to Childx: Talking Zika with a Stanford infectious disease expert, and Zika and reproductive rights: new geographies, similar concerns