Zika virus found in fetal brain
The Zika virus, thought to be responsible for a surge in birth defects in Brazil, has been found inside the abnormally small brain of an aborted fetus at roughly 29 weeks of gestation, a team of researchers reported Wednesday in the New England Journal of Medicine.
An autopsy of the aborted fetus revealed a brain that had virtually none of the folds and convolutions that would usually be seen on the brain’s surface in a fetus at that point in its development. Calcium deposits were evident throughout the brain’s white matter – the tissue that connects neurons and brain regions to one another. And in several places, those calcifications displaced developing cortical matter.
The calcium deposits “resembled destroyed neuronal structures,” the researchers said.
The case, described by a team of pathologists, microbiologists and maternal-fetal medicine specialists at Slovenia’s University of Ljubljana, is the first published finding of Zika virus directly in brain tissue. Other unpublished findings have suggested scientists have found Zika in cerebrospinal fluid.
As such, the new report takes a major step toward filling in the picture of the Zika virus and its effect on fetal development. The team also reported it recovered the “complete genome” of Zika virus from the fetal brain.
The woman who carried the fetus reported that she had suffered an illness with fever and rash – symptoms consistent with Zika virus infection – near the end of her first trimester of pregnancy, when she was living in Brazil. After an ultrasound performed at 29 weeks of gestation revealed microcephaly in the fetus and calcium deposits throughout the brain and placenta, the patient requested the termination of the pregnancy.
The autopsy also revealed a fetus that was very small for its gestational age, an indication the placenta is also somehow damaged in Zika infection. Notably, the researchers failed to find the virus in the fetus’s other major organs or tissues.
Finding Zika virus inside the brain – and only in the brain – of this developing fetus with severe abnormalities is a crucial step in demonstrating the role of the virus in causing the congenital birth defects. It also suggests the virus replicates robustly in the brain, but not elsewhere, the researchers wrote.
It’s rare for viruses to enter the fetal brain, a feat that requires crossing the placental barrier between mother and child as well as the blood-brain barrier of the developing baby. A developing fetus’s brain is often referred to as a “privileged site,” protected from infection by a biological phalanx of locks and keys.
“This is a huge step toward proving this virus causes microcephaly,” said Dr. Charles Chiu, director of a viral diagnostic laboratory at the University of California, San Francisco. “It doesn’t prove it formally,” Chiu added, as many further scientific hurdles need to be cleared before Zika is shown as the direct cause of the birth defects. “But it’s hard now to argue that the virus has nothing to do with the fetal complications we’ve seen in Brazil, and that’s important,” he said.
Researchers conducted tests and inspected fetal tissue under electron microscope, and by both means identified the Zika virus. It’s not clear whether they found any evidence of other infections, such as rubella, cytomegalovirus or toxoplasmosis, that can also cause similar birth defects.
The recovery of Zika virus that would permit a full genomic analysis also sets the stage for many insights. Scientists sequencing the viral genome will be able to compare it to Zika virus collected in other outbreaks, and that circulating elsewhere, to see if it has changed or if varying strains of the virus exist.
Chiu said having the genetic material associated with a clear case of microcephaly would play a key role in the development of better field tests to detect the virus, and potentially of antiviral drugs and vaccines to fight off or prevent Zika infection.