As horrible as Zika is, causing severe brain abnormalities in developing fetuses, a new study in mice published in Cell Stem Cell on August 18, 2016 suggests the consequences of infection with this rapidly spreading virus could be much worse than we imagined. It may affect adult brains as well.
The Zika virus wreaks havoc on fetal brains by infecting a type of brain stem cell known as neural progenitor cells. As fetal brains grow and develop, these cells differentiate into the various types of neurons and glia (cells that provide support and protection for neurons) that make up the adult brain. It is believed that these mature types of brain cells are more resistant to Zika explaining why adults seem to be protected from the severe brain damage and resultant microcephaly (small head) that is found in newborns who were infected while they were fetuses.
It turns out that adults don’t lose all of their neural progenitor cells (NPCs). Pockets of them remain in two different areas of the adult brain: the anterior subventricular zone (SVZ) of the forebrain and the subgranular zone (SGZ) of the hippocampal dentate gyrus. These NPCs are the source of neurogenesis (creation of new neurons) in adults. Neurogenesis is important to replace neuronal cells that are lost or damaged throughout adulthood—this is particularly important for learning and memory.
The mouse study
In an effort to learn about the impact of the virus on mature brains, scientists from The Rockefeller University and La Jolla Institute for Allergy and Immunology infected the blood of adult mice with Zika virus. When the brains of the infected mice were compared to control mice, the researchers discovered that Zika preferentially infected and killed neural progenitor cells.
According to one of the study authors, Joseph Gleeson, a professor at Rockefeller University,
“Our results are pretty dramatic…the virus wasn’t affecting the whole brain evenly, like people are seeing in the fetus. In the adult, it’s only these two populations that are very specific to the stem cells that are affected by virus. These cells are special, and somehow very susceptible to the infection.”
Why haven’t most adults shown symptoms?
Sujan Shresta, a professor at the La Jossa Institute of Allergy and Immunology and one of the study authors, says “the majority of adults who are infected with Zika rarely show detectable symptoms.” Although we don’t know exactly why, scientists have speculated that “healthy humans may be able to mount an effective immune response” not shown in the type of mice used in the experiment. It could also be that clinicians, not expecting neurologic deficits in adults, have not looked closely enough to detect subtle findings. It is also possible that difficulties with learning and memory may only show up over time as healthy neurons die of other causes and fail to be replaced because Zika-related impairment of neurogenesis. Further research, both basic science and clinical studies, are urgently needed.
The public health response
This study, although preliminary and in mice, should drastically alter how we think about the public health response to Zika. Currently, beyond mosquito control efforts, public health measures are largely directed at pregnant women and their partners, couples thinking about getting pregnant, and men and women of reproductive age. If it is confirmed that Zika can cause brain damage in older adults as well, we will have to amp up mosquito control and vaccine development efforts far beyond what we are currently doing. It will be impossible to keep everyone out of areas with Zika-infected mosquitoes.
This means Congress will have to stop dallying around and, perhaps, even come back from vacation early so they can pass a serious funding bill. This is not the time to play party politics; the consequences of an unchecked Zika epidemic are enormous. Zika containment should not be a red or blue issue. Mosquitoes don’t really care who they bite as long as they have blood.