UNC Researchers vs. Zika Outbreak

UNC faculty Elizabeth Stringer. MD, (right) and Sylvia Becker-Dreps, MD, MPH, (left) during travels to the UNC Program in Nicaragua to contribute to research efforts to understand Zika infections.

UNC faculty Sylvia Becker-Dreps, MD, MPH, (left) and Elizabeth Stringer, MD, (right) during travels to the UNC Program in Nicaragua to contribute to research efforts to understand Zika infections.

By Bradley Allf, Features Writer, UNC Institute for Global Health & Infectious Diseases

Researchers at UNC are working across departmental lines in order to answer questions about the emerging Zika virus outbreak. The mosquito-borne virus is garnering much international attention, particularly due to its potential to cause birth defects. Yet compared to related viruses like dengue, little is known about Zika virus. Researchers and lab groups at UNC from many different departments are working at the forefront of this outbreak to answer some of the most urgent questions about Zika virus and its effects on human health.

Helen Lazear, PhD, is one of those researchers. She works in the UNC Department of Microbiology and Immunology studying arboviruses— that is, viruses that are transmitted by arthropods. Zika virus, which is primarily spread by mosquitos, is part of a family of arboviruses known as “flaviviruses.” This group includes dengue virus, West Nile virus, and yellow fever virus, among others.

So why is so little known about Zika? Though the virus was discovered in 1947, it was not linked to any serious outbreaks of disease until quite recently.

“It was really in about 2007 that the virus started getting more attention. At that point it was introduced into Micronesia and caused a large outbreak there. And it proceeded to spread across the South Pacific,” says Lazear.

Though the virus spread rapidly, the symptoms of infection were relatively mild and flu-like. Many infected individuals didn’t show any symptoms, but of those that did the most common complaints included fever, headache, and a rash.

Then, in 2015 the virus was introduced to South America. That’s when doctors started noticing an association between the virus and something much more serious: birth defects.

“For Zika virus, the reason this is getting so much attention is because of its ability to cause birth defects, which I have to say is entirely unexpected. Based on what we know about the viruses related to Zika virus, there was no reason to think that Zika virus would cause birth defects,” says Lazear.

Only a small fraction of women infected with the virus have given birth to children with birth defects. Yet the evidence is mounting that Zika infection does lead to an increased risk that pregnant women will give birth to a child with birth defects including microcephaly, where babies are born with abnormally small heads. This evidence recently led the World Health Organization (WHO) to update its language on the matter, calling the link between Zika virus and birth defects a “scientific consensus.” There is also growing evidence linking Zika virus and a debilitating neurological disorder called Guillain-Barre Syndrome, though researchers have been aware of this relationship for some time.

Countries in infected areas are clearly concerned about Zika’s implications for pregnancy, even leading El Salvador down the dubious route of advising women against getting pregnant until 2018. Such a response can be understood in light of the scale of the epidemic (which is now an order of magnitude larger than any previous Zika outbreak) paired with the very little that researchers know about the virus.

As Myron Cohen, MD, UNC Chief of Infectious Disease, described in a recent “Chair’s Corner” podcast, “What relaxes our species and reassures our species is knowing the rules. The rules of an infection. The probability of a transmission event, the consequences of a transmission event, and the interventions that are possible to prevent, treat or cure disease.”

With Zika virus, we still don’t know many of the rules. But thanks in part to the ongoing work of a number of researchers at UNC, our knowledge of Zika virus is rapidly expanding, which will help the global community better deal with this epidemic.

Click here to listen to an episode of Public Health Behind the Scenes about the intersection of public health and Zika, produced by UNC Gillings School of Global Public Health and Gillings Global Gateway.

Helen Lazear, PhD, is part of a team that recently developed a mouse model to study Zika virus.

Helen Lazear, PhD, is part of a team that recently developed a mouse model to study Zika virus.

Virology
Lazear and the rest of her team are working to answer some of the essential questions about the virology of Zika. “In my lab we’re interested in a couple of aspects of Zika virus. A lot of it is basic virology and pathogenesis work because nobody’s done a lot of research on this virus before. There’s a lot of really basic things we don’t know about how this virus infects cells, and how it replicates and spreads,” she says.

Just this month Lazear was the lead author on a paper in Cell Host & Microbe describing how she helped a team develop a new mouse model that can be infected with Zika virus in order to learn more about the virus. This model could eventually be used to test a Zika vaccine, or other treatments for infected individuals.

Other groups at UNC are interested in why Zika has emerged so suddenly. Ralph Baric, PhD, heads a lab interested in viral genetics. This group is interested in better understanding how the virus has evolved over time, and whether those evolutionary changes to the viral genome could have led to the current Zika outbreak.

Linking Zika and Dengue
In addition to virology research, Lazear’s group is working alongside UNC researchers with expertise in dengue virus to better understand how dengue immunity could change how Zika affects the body.

Dengue is the closest viral cousin to Zika. It is also the most prevalent mosquito-borne virus in the world and is common across much of the area affected by the current Zika epidemic. Dengue virus, of which there are four types, generally causes much more severe symptoms than the Zika virus (however, it is not known to cause birth defects).

If a person gets infected with one type of dengue, they develop an immunity to that strain for the rest of their life. But if they get infected with a different type of dengue, they can develop symptoms again—often more severe symptoms than they had during the first dengue infection.

Aravinda de Silva, PhD, heads a lab at UNC that studies dengue. He is concerned that Zika might cause similar adverse reactions in people with previous dengue exposure. Said de Silva at a recent conference on Zika hosted by the UNC Institute for Global Health & Infectious Diseases (IGHID).

“A lot of people that are dengue immune are getting exposed to Zika. And there may be immune interactions between dengue and Zika that might enhance disease. And the answer is even more complicated because you have to think about someone who’s had only one dengue infection and then they get Zika, so their second infection is Zika. Or someone who’s had multiple dengue infections, what happens if they get Zika versus someone who’s had a flavivirus vaccine?”

De Silva’s research suggests that previous infection with dengue could change, and potentially worsen, how Zika virus affects the body. The lab is also investigating the development of tools for diagnosing Zika, which is also complicated by the virus’s close relatedness to the widespread dengue virus. Because dengue and Zika are so similar, developing diagnostics that can reveal Zika infection, but not previous dengue infection can be tricky.

Elizabeth Stringer, MD, is an OB/GYN at UNC. Zika has been linked to causing microcephaly in infants.

Elizabeth Stringer, MD, is an OB/GYN at UNC. Zika has been linked to causing microcephaly in infants.

Epidemiology
UNC faculty are also working to develop a way to track the effects of Zika by establishing ties with hospitals and clinics in affected areas. In March, a UNC group traveled to León, Nicaragua, in order to learn more about the local response to the outbreak. Elizabeth Stringer, MD, a Maternal and Fetal Medicine doctor, was one of the UNC researchers on the trip.

“We were looking at how their prenatal care is delivered and looking at how we could set up a cohort of pregnant women to study Zika virus,” says Stringer. “That means a group of patients that we follow throughout their pregnancy and then test for Zika at different intervals to see how many acquire the disease and how many fetuses get infected.”

A cohort like this is exactly what is needed to answer some of the most pressing questions about Zika. For example, such a cohort could reveal the likelihood of an infected mother passing the virus on to her fetus, and the likelihood that a Zika-infected fetus will develop birth defects.

These cohorts could also help answer another pressing question: could Zika virus be contributing to milder birth defects that have as of yet gone unnoticed? That’s an important question according to Matthew Collins, MD, PhD, an Infectious Disease Fellow at UNC who also went on the trip to León.

“Some of the key questions that are still noteworthy are spectrum— the possibility that microcephaly is at the severe end of a spectrum of adverse effects that a developing fetus may experience.” He continues, “we have a very low threshold for tolerance to adverse events surrounding pregnancy and rightfully so. So trying to understand the magnitude of that risk is a big outstanding question and we don’t quite know what that is.”

Already, reports are circulating that Zika infection is associated with other problems with fetal development and childbirth, such as blindness and premature birth. As we learn more about how Zika virus affects humans, potentially through pregnancy cohorts like this one, we will continue to learn what risks the virus poses to humans in the long-term.

A multidisciplinary team of researchers and clinicians at UNC is studying Zika.

A multidisciplinary team of researchers and clinicians at UNC is studying Zika.

A Multi-Departmental Approach
When asked how concerned people should be about the virus, Collins responded “with people, fear naturally comes from the unknown and there’s just not a lot of extensive, quality data about Zika right now.”

Fortunately, UNC is well-positioned to begin the process of changing that, by learning more about the Zika virus in order to combat the ongoing epidemic. Says Lazear,

“UNC really is a great place for Zika virus research because we have a lot of people from different disciplines and backgrounds that are relevant to the current outbreak. So we have a group of virologists, of infectious disease experts, experts in maternal and fetal medicine, public health, and vector-borne diseases. We are able to take advantage of a lot of varied expertise that’s all relevant to the current outbreak.”

This group of researchers is working across departmental lines to develop a better understanding of Zika, and many researchers are even modifying their own research goals to better answer questions about the virus.

This research will no doubt be used to improve the response to the outbreak in Latin America and the Caribbean. But according to Lazear, it will also be used to help us better understand how to deal with the next viral epidemic.

“The phenomenon of an Old World arbovirus being introduced to the New World and causing impacts on human health— this isn’t new. We saw this happen a few years ago when chikungunya virus was introduced into the Caribbean in 2013, we saw it with West Nile virus in 1999, dengue virus before that, and originally when yellow fever virus was introduced to the Western Hemisphere with the slave trade.”

She continues, “Today we’re talking about Zika virus, but the lessons about this virus can be informed from what we’ve learned from previous outbreaks, and will likely be able to be applied to future outbreaks as well.”