Zika investigators now believe that microcephaly in newborns and Guillain–Barré syndrome in adults may be just the most obvious disorders caused by the mosquito-borne virus, according to a report from Reuters. Fueling that suspicion are recent discoveries of serious brain and spinal cord infections, including encephalitis, meningitis, and myelitis, in people with Zika virus infection.
Scientists have two opinions on why these new maladies are making an appearance. The first theory is that, as the virus spreads through large populations, it is revealing effects that were overlooked in earlier outbreaks in remote and sparsely populated areas. The second theory is that the newly detected disorders are more evidence that the virus is evolving.
“What we’re seeing are the consequences of this virus turning from the African strain to a pandemic strain,” Dr. Peter Hotez, dean of the National School of Tropical Medicine at Baylor College of Medicine, told Reuters.
Zika’s hypothesized attraction to human neural stem cells may come from its ability to hijack a protein found on the surface of those cells, using it as an entryway to infection, according to an article published in the March 30 online issue of Cell Stem Cell.
Researchers at the University of California in San Francisco showed that the AXL surface receptor, normally involved in cell division, is abundant on the surface of neural stem cells, but not on neurons in the developing brain.
The neural stem cells that express AXL are present only during the second trimester of pregnancy. These cells, called radial glial cells, give rise to the variety of cell types (e.g., neurons and astrocytes) that help build the cerebral cortex. The researchers also found AXL expressed by the stem cells of the retina. Disruption of this range of cell types is consistent with the numerous symptoms associated with Zika virus infection in the developing fetus—including microcephaly, a brain lacking in folds, and eye lesions.
“While by no means a full explanation, we believe that the expression of AXL by these cell types is an important clue for how the Zika virus is able to produce such devastating cases of microcephaly, and it fits very nicely with the evidence that’s available,” said senior author Dr. Arnold Kriegstein.
The suspicion that Zika acts directly on nerve cells began with autopsies on aborted and stillborn fetuses, which showed that the virus replicates in brain tissues. In addition to microcephaly, researchers found other abnormalities linked with Zika, including fetal deaths, placental insufficiency, fetal growth retardation, and injury to the central nervous system.
Zika experts also are worried that exposure to the virus in utero may have hidden effects, such as behavioral problems or learning disabilities, that are not apparent at birth.
“If you have a virus that is toxic enough to produce microcephaly in someone, you could be sure that it will produce a whole series of conditions that we haven’t even begun to understand,” Dr. Alberto de la Vega, an obstetrician at University Hospital in San Juan, Puerto Rico, said in the Reuters report.