Zika Research Reveals Virus May Negatively Impact Adult Neural Stem Cells

Understanding of the Zika virus’ effect on the human brain continues to expand—and the news is troubling to say the least.

Using mouse models, researchers from the Laboratory for Pediatric Brain Diseases/Howard Hughes Medical Institute at Rockefeller University; Rady Children’s Institute for Genomic Medicine, University of California, San Diego; the La Jolla (California) Institute for Allergy & Immunology; and the Del. E. Webb Center for Neuroscience, Aging and Stem Cell Regeneration/Sanford Burnham Prebys Discovery Institute have determined that adult as well as fetal neural stem cells are vulnerable to the neuropathology associated with the mosquito-borne virus that has plagued Brazil and the Caribbean and has recently surfaced in Florida. The infection can lead to cell death and reduced proliferation. Their findings were published online on August 18 in the journal Cell Stem Cell.

“The more we learn about this virus the more we realize that we don’t know much about it and how it affects those infected,” study co-author Sujan Shresta, PhD, Associate Professor at the La Jolla Institute for Allergy and Immunology told Contagion. “Our study suggests that the impact of the infection may be important in children whose brains are developing and maybe even in the brains of adults as well.”

Dr. Shresta has devoted much of her research efforts toward developing mouse models for a number of infectious diseases, including another mosquito-borne virus—Dengue fever. For this study, she and her colleagues infected 5- to 6-week old mice with an Asian strain of Zika via retro-orbital injection to replicate the blood-borne route of arbovirus transmission. They screened the serial coronal sections of the whole brain of infected and mock-treated mice with the monoclonal 4G2 antibody and observed in infected (but not mock-treated) mice what they describe as “dramatic immunoreactivity in proximity to the subventricular zone of the anterior forebrain, as well as the subgranular zone of the hippocampus,” the two regions that maintain stem cell populations throughout adulthood. Notably, they also found that in other regions of the brain there was less immunoreactivity, which they believe suggests “a particular tropism of the virus for proliferative regions of the brain.” In fact, quantification across major brain regions revealed statistically significant selective vulnerability to these proliferative zones.

To date, of course, Zika has been classified as a “transient infection” in adults that carries no significant long-term complications. However, the findings of the Cell Stem Cell research suggest that there may, in fact, be long-term effects of the disease for adults. Dr. Shresta believes there may be implications for infected adults in terms of learning and memory as they age as well as in the cognitive development of children. Still, she also emphasizes that it is premature to draw firm conclusions from this single study, and that the findings will need to be replicated before the full effects of Zika on the brain are known.

“For now, our study can perhaps alert physicians seeing children with a history of Zika virus infection” who may be exhibiting atypical “cognitive behaviors,” she said. “However, it’s important to note that we used only one mouse model and only one strain of the virus in our study, so we need other researchers in other laboratories, hopefully, to replicate our findings using other mouse models and other strains of [Zika]. Clearly, it’s vital that we expand our knowledge of this virus and its impact on the human brain.”

Brian P. Dunleavy is a medical writer and editor based in New York. His work has appeared in numerous healthcare-related publications. He is the former editor of Infectious Disease Special Edition.