The Zika virus is linked to rare neurological problems in adults – now researchers want to know if it can cause memory-harming brain damage, too.
There’s plenty of evidence infection Zika can cause brain damage in unborn babies. The virus is linked to microcephaly, a birth defect marked by a smaller-than-normal brain and head and serious neurological problems. Although adults seldom experience anything other than minor symptoms from the virus, a few have been diagnosed with conditions involving the brain and nervous system.
For example, some adult Zika patients developed Guillain-Barré syndrome, which causes neurological symptoms, including weakness and, rarely, paralysis. A couple of Zika patients also developed acute disseminated encephalomyelitis , a serious neurological illness associated with inflammation in the brain and spinal cord.
Now research from Rockefeller University and La Jolla Institute for Allergy and Immunology suggests the virus could potentially damage adult brain cells believed to be critical for memory and learning.
"Based on our findings, getting infected with Zika as an adult may not be as innocuous as people think," said Joseph Gleeson, MD, who directs Rockefeller’s Laboratory of Pediatric Brain Disease and headed the study.
Before fetal brains develop fully into organs with specialized areas, they are comprised of neural progenitor cells that normally become fully formed brain cells (neurons) over time. It’s believed Zika can damage and destroy many neural progenitor cells in unborn babies as they develop, reducing brain size. Although healthy adults have fully formed neurons, they still retain niches of neural progenitor cells located in parts of the brain important for memory and learning. These neural progenitor cells can replace damaged or lost neurons in adults, according to the researchers. But it turns out they may be vulnerable to Zika.
Gleeson and his research team studied mice engineered to mimic Zika infection in humans. Using fluorescent biomarkers that made adult neural progenitor cells in the animals’ brains light up, the scientists discovered these cells, located in areas of the brain important for memory in both mice and humans, were damaged by the virus.
“Zika can clearly enter the brain of adults and can wreak havoc," said researcher Sujan Shresta, PhD, an infectious disease specialist at the La Jolla Institute of Allergy and Immunology. "But it's a complex disease — it's catastrophic for early brain development, yet the majority of adults who are infected with Zika rarely show detectable symptoms. Its effect on the adult brain may be more subtle, and now we know what to look for."
It’s important to remember that so far this research has only involved mice. However, it raises the possibility there may be as yet unknown effects of Zika infection over the long term that scientists and doctors need to consider, according to Emory University School of Medicine scientist and professor of human genetics Peng Jin, PhD.
“I would keep my mind open. There might be some subtle effect or long-term alterations caused by Zika that could require years of works to recognize,” said Jin, whose research includes neurodevelopmental and neurodegenerative disorders. “We need to figure out how Zika damages the brain and what cell types Zika primarily targets,”
Infections with viruses related to Zika are known to potentially cause brain damage, but these infections are typically much stronger. This might explain why microcephaly is observed with Zika but not the other brain-impacting viruses, according to Jin. The more aggressive viruses in the same family as Zika probably cause more miscarriages, whereas unborn babies may be more likely to survive Zika but end up with damaged brains from the virus.
(You can see images of what Zika can do to the brains of babies here.)
Not every pregnant woman infected with Zika has a baby with birth defects, and adults who acquire Zika typically have few no symptoms – so that raises questions about why Zika affects some people severely and others not much at all. Are there co-factors, such as genetic or environmental influences, that determine who is at risk for Zika-caused brain and neurological problems?
“It is too early to tell,” Jin said. “Both genetic and environmental factors will certainly play some role. Even for microcephaly, Zika infection does not lead to the condition 100 percent of the time. It will be interesting to determine whether any genetic components can modulate the phenotype (the properties of the virus, including how it develops and behaves) caused by Zika.”
While scientists continue to learn more about Zika’s potential impact on health, they are also coming closer to finding ways to prevent it. Scientists at Washington University School of Medicine in St. Louis have pinpointed antibodies that protect against infection with the virus — raising the odds a vaccine, better diagnostic tests, and even antibody-based therapies to treat Zika can be produced.
“It is encouraging to see the development of antibodies against Zika,” Jin said. “In addition, it would be helpful to identify the small molecules that could prevent the replication of Zika in mammalian cells, which could potentially prevent further amplification of this virus once it infects a human.”
March 31, 2020
Christopher Nystuen, MD, MBA