This visual abstract shows the findings of Li et al., that peripheral ZIKV exposure in a mouse model can infect adult neural stem cells in the brain, leading to cell death and reduced proliferation. Thus, in addition to impacting fetal development, ZIKV infection may also have negative effects on the adult brain. Courtesy of Li et al./Cell Stem Cell
Zika infection kills off neural stem cells in adult mice bred to be vulnerable to the virus, researchers at the Rockefeller University and the La Jolla Institute for Allergy 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 rodents.
Most human adults don't show symptoms when infected with Zika, aside from a fever or rash. Increased incidence of Guillain-Barré Syndrome 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 embryo.
"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 disorders at the Rockefeller University. "We found that there is something special about these precursor cells that allow the virus to gain entry and dramatically affect their proliferation."
He collaborated 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 immediate call to action on Zika.
Shresta's lab created the Zika mouse models by knocking out the antiviral molecules 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 investigators 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 implicated in learning and memory," Shresta says. "We don't know what this would mean in terms of human diseases, or if cognitive 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.
This work was supported by the National Institutes of Health, the Simons Foundation Autism Research Initiative (SFARI), the Howard Hughes Medical Institute, the California Institute of Regenerative Medicine, and a Druckenmiller Fellowship from New York Stem Cell Foundation.
Source: Cell Press