A recent Yale study may help chronicle the spread of Zika throughout the developing brain.

Researchers at the Yale School of Medicine have found new insights into how the Zika virus first enters the brain. Zika, an RNA-based virus, infects the brains of fetuses in the wombs of women already affected by the virus, causing a brain developmental disorder called microcephaly in the infants. The research shows that the virus enters the brain via cells called astrocytes before rapidly spreading to neurons. The study, called “Zika virus targeting in the developing brain,” was published in the Journal of Neuroscience in January 2017.

“We found that the first cell infected was an astrocyte,” said Anthony van den Pol, one of the lead authors of the study. “We think that the virus can then replicate in these astrocytes and then be released by the astrocytes and then infect neurons.”

According to the study, researchers injected several newborn mice with a certain strand of Zika virus, followed by a Zika antiserum raised in rats. This antiserum was used to detect where the virus was within the brain, according to van den Pol. The study found that the first cells infected by the virus were glial cells — a type of brain cell distinct from neurons — particularly astrocytes.

“Cells, to some degree, can be divided into two types in the brain. One is neurons, and there are many different types of neurons, and the other is glial cells,” said van den Pol. “These are cells that are considered to be more electrically silent and play a bunch of roles not related to neuron transmission. An astrocyte is often conceived as a supporting cell that helps the neuron in a lot of functions.”

One of the main reasons astrocyte cells may be infected first, according to the study, is that they have end feet that wrap around blood vessels, making them an accessible first target for Zika arriving from the bloodstream. From there, the virus spreads to neurons throughout the brain. According to van den Pol, another interesting finding of the study is that Zika seems to enter the brain through many different sites, as opposed to just one.

“It wasn’t one or two single entrances into the brain which then spread,” said van den Pol. “It seemed to be many, many single cells isolated throughout the brain that showed signs of Zika infection.”

These findings may provide an excellent parallel to how Zika enters the brains of human fetuses. According to van den Pol, the brain of a newborn mouse is roughly developmentally equivalent to a human brain during the second trimester of pregnancy. The study opens up the additional possibility that Zika may lead to other long-term negative effects besides microcephaly. More nuanced infections of Zika may not cause severe problems for an infant at birth, van den Pol said, but could manifest themselves in substantial problems later in life.

Moving forward, van den Pol said he hopes to continue to help in the fight against Zika.

“The rapid movement from not being here to all of a sudden having a very strong and powerful adverse disposition here, particularly in Brazil, is something that called for experimental attention,” van den Pol added. “In addition to my lab, there’s a number of other labs at Yale who’ve been working with Zika, and there’s dozens and dozens of labs, both in this country, and in other countries, that are trying to get a handle on how to combat the virus and understand how it does what it does.”

According to the National Institutes of Health, Zika in nonpregnant people is generally expelled after several weeks, with illness lasting several days to a week.

JOE CLASS