Zika infection kills off
neural1 stem cells in adult mice bred to be vulnerable to the virus, researchers at the Rockefeller University and the La Jolla Institute for
Allergy2 and Immunology report August 18 in Cell Stem Cell. It has yet to be studied whether the death of these cells has any short or long-term effects in the
rodents3. Most human adults don't show symptoms when infected with Zika, aside from a fever or rash. Increased incidence of Guillain-Barré
Syndrome4 has been associated with the virus, raising questions about whether Zika has a negative impact on the adult brain. The virus is known to be particularly attracted to neural stem cells, but adults have smaller populations of these cells compared with a developing
embryo5.
"We wondered if Zika would have more of an effect on newly generated neurons than any other parts of the adult brain," says Joseph Gleeson, a physician who studies brain
disorders6 at The Rockefeller University. "We found that there is something special about these
precursor7 cells that allow the virus to gain entry and dramatically affect their proliferation."
He
collaborated8 with Sujan Shresta, who studies infectious disease at the La Jolla Institute for Allergy and Immunology, after hearing her give a lecture to students on the mouse models she's developed for Dengue virus. Compared to Dengue, Zika has some unique traits (e.g. it crosses the placenta, it is sexually transmitted, it stays in the body), but because both are closely related flaviviruses, the researchers collaborated on adapting the work to the
immediate9 call to action on Zika.
Shresta's lab created the Zika mouse models by knocking out the antiviral
molecules10 that naturally help mice resist infection. The researchers then injected a modern Zika strain into the bloodstream. Three days later the brains of the mice were harvested and antibodies were used to identify the presence of Zika. The
investigators11 observed that viral particles were surrounding the neural stem cells. Looking at brains over time, there was a 4- to 10-fold drop in adult stem cell proliferation.
"Adult neurogenesis is
implicated12 in learning and memory," Shresta says. "We don't know what this would mean in terms of human diseases, or if
cognitive13 behaviors of an individual could be impacted after infection."
The collaborators will next be investigating changes in neural stem cell populations over time in the mouse brain as well as whether the strain of Zika impacts results.