Zika Research in Monkeys Provides Insight into How the Virus Damages the Human Brain

Researchers at the University of Washington may have gained new insight into exactly how Zika virus infection damages the developing brain of the fetus in pregnant women.

Since the 2014 outbreak of the mosquito-borne virus in Brazil, scientists investigating the health effects of the disease as well as clinicians at the frontlines treating patients have observed microcephaly, a developmental brain defect, in babies born to infected pregnant women. Reports suggest that more than 1,800 children in Brazil have been born with the defect, which can cause hearing loss and other complications and has been linked with Zika, although questions remain as to precisely how the virus causes it.

However, the multidisciplinary team at the University of Washington, which included experts in obstetrics and gynecology as well as pediatrics, pathology, radiology, and other specialties, seems to have unraveled at least part of the mystery. Their findings were published online on September 12 by the journal Nature Science.

For the experiment, the researchers infected a pregnant female pigtail macaque monkey with an Asian strain of the Zika via injection. The monkey had been otherwise healthy prior to infection.

According to Kristina Adams Waldorf, MD, professor of obstetrics and gynecology at the University of Washington and the study’s lead author, the pigtail macaque was selected because its brain develops much in the same way as the human brain; for example, each have similar proportions of gray and white matter. The structure of the primate placenta is also similar to that of humans, she added. Thus, the study was able to closely mimic a Zika infection during the third trimester of pregnancy, enabling Dr. Adams Waldorf and her team to examine how the virus impacts a developing fetus.

They noted that periventricular lesions developed in the fetal brain within 10 days of infection and evolved asymmetrically in the occipital—parietal lobes. Fetal autopsy revealed Zika virus in the fetus’ brain matter as well as significant cerebral white matter hypoplasia, periventricular white matter gliosis, and axonal and ependymal injury, suggesting that the white matter of the monkey’s fetal brain stopped developing within 3 weeks of infection, even though the mother monkey never displayed outward symptoms of infection such as fever or rash. The authors also identified vision problems and Zika virus genetic material in the eyes, liver, and kidneys of the fetus. If disease progression had been allowed to continue, they believe, the macaque fetus would have been born with microcephaly.

“This is truly a breakthrough,” Dr. Adams Waldorf told Contagion. “Using the pregnant macaque model, we can understand what is happening during viral infection throughout all of the tissues from the fetus and the mother in early and late infection. What we modeled was an arrest of brain growth in late pregnancy, which has been reported in many human cases of Zika.”

She added that the study also demonstrates that Zika virus crosses the placenta from a mother to the brain of the fetus. In fact, the authors found more evidence of the virus in the brain of the fetus than in the brain of the mother. They believe that their work confirms the utility of the pigtail macaque as a model for human disease and, specifically, congenital Zika virus syndrome as part of efforts to identify therapies to prevent birth defects.

“It is very difficult to control [Zika], which continues to spread,” Dr. Adams Waldorf said. “If anything, pregnant women in the US are not getting the message to stop traveling to [areas] with local transmission of Zika. Hopefully, press coverage surrounding our findings will add to this message about how dangerous Zika truly is for pregnancy.”

Brian P. Dunleavy is a medical writer and editor based in New York. His work has appeared in numerous healthcare-related publications. He is the former editor of Infectious Disease Special Edition.