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 Other, unpublished, findings have suggested scientists have found Zika in cerebrospinal fluid.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 they 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 that 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 that 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 UC 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 assays 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 that 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.
With the viral sequence firmly in hand, scientists can design laboratory clones of the virus implicated in this case of microcephaly. Those in turn could be reproduced indefinitely and could be used to infect lab animals. That would offer scientists both a window on how the virus affects a fetus, and a means of testing the effectiveness of drugs or vaccines against infection.
The report comes just a day after researchers at a Brazilian hospital reported they had found ocular abnormalities in 35% of 29 infants born with microcephaly. Four in five of the newborns' mothers reported having suffered symptoms during pregnancy consistent with Zika infection.
The babies' retinas and optic nerves were found to have structural abnormalities, often on both sides, the researchers reported in JAMA Ophthalmology. Since they were unsure of whether such abnormalities might have occurred in the absence of microcephaly, they stopped short of urging all newborns in areas where Zika virus is newly circulating to be screened for the eye issues.
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