Zika Infects Lab-Grown Brain Cells, Strengthens Link To Microcephaly

In a study that strengthens a link between Zika and rare birth defects known as microcephaly, US researchers said the mosquito-borne virus can infect neural stem cells crucial for brain development in the lab.

The researchers, led by Chinese-born Guoli Ming and Hongjun Song of the Johns Hopkins University and Hengli Tang of Florida State University, with Peng Jin at the Emory University, worked around the clock for a month to conduct the study, after the World Health Organization declared microcephaly a public health emergency of international concern in early February.

“What I want to emphasize is this is a very first step. We did not directly conclude that Zika infection causes microcephaly,” said Professor Tang, a virologist, whose study was published Friday in the US journal Cell Stem Cell.

“What we show is that the Zika virus infects neuronal cells in dish that are counterparts to those that form the cortex during human brain development. We still don’t know at all what is happening in the developing fetus,” added Professor Song, a neuroscientist and stem cell biologist.

These findings may correlate with disrupted brain development, but direct evidence for a link between Zika and microcephaly is more likely to come from clinical studies, the researchers noted.

In the study, the researchers derived the stem cells, called cortical neural precursors, from human induced pluripotent stem cells and found that the Zika virus easily infected these cells.

One concerning discovery was that the cells that Zika infected became factories for viral replication. From a single infection, the virus particles spread through a plate of stem cells within a span of three days, resulting in cell death or disruption of cell growth, they said.

There’s no evidence that the cells are employing antiviral responses, which means we don’t know whether or how the virus is being cleared from the precursor cells, said Ming, a neuroscientist interested in brain disorders like microcephaly.

Next, the researchers planned to grow mini-brains from the stem cells to observe the long-term effects of Zika infection on neural tissue and to screen for potential therapeutics.

“We are trying to fill the knowledge gap between the infection and potential neurological defects,” said Tang, whose lab studies RNA viruses like Zika, Dengue, and hepatitis C virus. “The questions we address here are among the very first questions people want to know the answers of.”

Mark Schleiss, professor at the University of Minnesota, who was not involved in the study, hailed the results as “a big step in the right direction” in terms of understanding the pathogenesis of Zika.

“Recent papers have found virus particles in fetal brain tissue and amniotic fluid, so as the scientific data has emerged most scientists have not had any doubt that the Zika virus is responsible for the brain injury,” Schleiss said.

“But as the Zika virus story has unfolded there has been speculation about the mechanism, which this study addresses.”

Noting more confirmatory epidemiologic data is still needed from Zika endemic areas, Alyssa Stephenson-Famy, assistant professor at the University of Washington, said: “This is exactly the kind of research that we need to demonstrate a causative link and mechanism between the Zika virus and microcephaly.”

Zika is transmitted primarily through the bite of an infected Aedes species mosquito, which also spreads chikungunya, and dengue.

Symptoms include fever, rash, joint pain and red eyes, but severe disease requiring hospitalization is uncommon and case fatality is low.

There is no vaccine or medicine available for the virus.(PNA/Xinhua)  JBP/PJN