February 22, 2019
Supporting patient
Expert Q&A

How Does Zika Infect the Fetus?

by Jeanine Barone  

Eva Harris, PhD, is a professor of Infectious Diseases and Vaccinology in the School of Public Health at the University of California, Berkeley. She studies mosquito-borne diseases, such as Zika and dengue, and recently published a paper identifying two routes by which the Zika virus infects the fetus through the placenta. 
We talked with her about the Zika outbreak, her research, and why this virus has been so different to study than others.

Normally viruses don’t cross the placenta. Now you’ve shown two ways that the Zika virus infects the fetus, and at different points in pregnancy (one early, one later). Why is that important?

Generally the placenta acts as a barrier to viruses. Only a few viruses are associated with congenital birth defects, and Zika is one of them. We were surprised by the high levels of the virus we found in the cells of the amniotic membrane, or sac, in the human placental specimens we examined in the lab. This could help explain why the Zika virus is so successful in infecting fetus cells. With these types of viruses—Zika is a Flavivirus, like dengue—there is generally only a short time period when the virus is in the blood. Now we see in pregnant women that the virus reappears in their blood 16 weeks later, 21 weeks later. It’s surprising that the women test positive for the virus during their pregnancy long after infection. The placenta is readily infected and may be serving as a reservoir for the viruses.

What else are you currently working on?

NIH has sponsored a study called Zika in Infants and Pregnancy, or ZIP, in Brazil, Nicaragua, Colombia, Puerto Rico, and Guatemala. I’m running the study that’s starting soon in Nicaragua. This study could confirm the question of how Zika crosses the placenta to the fetus, as well as the degree of association between Zika virus infection and congenital birth defects. So little is known about this virus regarding transmission. I was in Nicaragua last week. It’s incredible to be there during a Zika outbreak. I’ve never seen anything like this; it seemed like literally everyone had Zika—our study personnel, our study subjects, my friends, their kids. Maybe saliva is contributing to the transmission, in addition to mosquitoes and sexual transmission. We just designed a household transmission study in which, after we identify a patient as infected with Zika, we go to their home and enroll and sample all the people in their house and follow them over time. This study will show when and for how long the Zika virus lasts in saliva, blood, and urine; the routes of transmission; and how long it takes for one person to infect another.

Zika is so new that we don’t even have a good case definition. Initially we included fever. But a lot of times there’s no fever. Now it’s a rash and fever and/or conjunctivitis (red eyes). But with dengue, a cousin of Zika, you see the rash at the end of the illness. So is the rash we see with Zika at the end, not at the beginning? Our study will answer these very basic questions that we don’t understand yet. We are also identifying which immune cells are being infected, and what the immune response looks like. We can connect fieldwork with sophisticated tools (initially developed for dengue) and hopefully answer such questions as how does the immune system respond? Does a previous dengue virus infection make Zika worse?

What does your research show as to what trimester is the greatest risk?

From the data available to date, I would believe that all the trimesters are at risk. However, the earlier a pregnant woman is infected, the more dramatic the effect, such as spontaneous abortion or microcephaly. Infection later in the pregnancy could still lead to more subtle effects in the baby: auditory, visual, cognitive, neurological, and developmental. That is what our study is about—following not only the pregnant women with Zika infections but their babies for at least one year (more pending funding).

After a very long delay, Congress has finally decided to allocate funds for research on Zika. What's your reaction?

Obama requested emergency funds in February 2016; Congress stalled for political reasons, and did not pass the bill until the end of September 2016. I still find it appalling that Congress blocked funding for this incredibly important global pandemic for seven months, delaying important progress. Zika will have a direct impact on the U.S., more so than Ebola. Nonetheless, I have been impressed at how rapidly the NIH has been able to get funds to Zika researchers; we and others have gotten money very quickly for certain critical studies. However, it’s money that NIH had to take from everywhere else, Ebola and all other diseases—previously allocated money that they are making available for Zika because there was no new money. NIH did the best it could under the circumstances.

How big of a problem will Zika be in the U.S. in the future?

I think it will not be as explosive as in other countries, which have huge mosquito infestations and high population densities. But Zika is found in over 25 different species of mosquitoes, and the main mosquito vector (the mosquito type that transmits the disease) is found in many states, so it will be a problem in the U.S., not just in Miami Beach but also the Texas border, anywhere there are mosquitoes. And we have sexual transmission.

Are we making progress with Zika?

Yes, absolutely. Being involved in the research, you see science happening rapidly and in real time. Now papers are coming out in several weeks, not eight months. Funding is given in weeks, not many months or years. Those working on international studies have been remarkably cooperative, sharing protocols, consent letters, surveys. As to progress, novel antiviral as well as existing drugs have been identified as possible treatments for Zika and are going into preclinical trials. A new vaccine is going into a clinical trial in Puerto Rico shortly. So instead of years, we’re talking months. The entire world is susceptible to Zika and the mosquito is ubiquitous. It’s a recipe for disaster.

Anything additional you would want readers to know?

I think Zika has been a real surprise to those of us who study infectious diseases. No one expected this to turn rapidly into a global health emergency. But the scientists and those working in the field, the public health workers, have come together. We are faced with a new global health emergency and the response has been amazing across the board. We are learning things rapidly and this will turn into messages for prevention, as well as treatments and vaccines.

This opinion does not necessarily reflect the views of the UC Berkeley School of Public Health or of the Editorial Board at BerkeleyWellness.com.

Also see Zika Virus and Travel.