The front lines of Zika

zika virus
Researchers have shown that the Zika virus (shown here) can infect neural progenitor cells critical for brain development.
In the field and laboratory, Emory experts have played a lead role in expanding a deeper global understanding of the complex Zika virus.

Zika virus was first discovered in Uganda in the 1940s, and two distinct lineages of it — African and Asian — diverged sometime in the second half of the 20th century. Studies indicate that strains currently circulating in the Western Hemisphere, which have been linked to microcephaly (babies born with small heads and underdeveloped brains) and Guillain Barre syndrome in adults, are more closely related to the Asian lineage. Zika virus was the first new cause of birth defects to be identified by the US Centers for Disease Control and Prevention (CDC) in 50 years.

In the field and laboratory, Emory experts took an early role in supporting research and control strategies for what quickly flared into a public health emergency, as the disease spread through Latin America, the Caribbean, and North America.

Emory scientists also have been part of a research collaboration that revealed molecular differences in how African and Asian strains of Zika virus infect neural progenitor cells, offering potential leads for how drugs could one day protect brain cells from death.

"The fact that Zika can pass through a woman’s placenta and affect her unborn child is a game-changer. That goes to your deepest fear and is about as unsettling as it gets," says Uriel Kitron, professor and chair of the Department of Environmental Sciences in Emory College and professor of environmental health and epidemiology at the Rollins School of Public Health. An expert in vector-borne diseases transmitted by mosquitoes, ticks, and other organisms, Kitron has worked in Brazil for years.

scientist standing in village near sites of stagnant water

Advancing knowledge on several fronts

In the past year, Emory has helped sharpen a deeper global understanding of the disease, pinpointing how it can infect and replicate in the placenta, working to identify and develop antivirals to treat the infection, studying mosquito transmission and surveillance, and hosting an international conference to encourage scientific collaboration and education.

Early on in the crisis, with funding from the Georgia Research Alliance, researchers working through Drug Innovation Ventures at Emory (DRIVE) and the Emory Institute for Drug Development (EIDD) began work to identify antivirals to treat the infection caused by the Zika virus.

According to George Painter, CEO of DRIVE and director of EIDD, “For the past three years, we have been synthesizing and developing antivirals against alphaviruses such as chikungunya and flaviviruses such as dengue. Since Zika is a flavivirus in the same family as dengue and hepatitis C, we can apply what we have learned working on alphaviruses and flaviviruses, as well as from our past success with treatments for HIV, hepatitis B, hepatitis C, and herpes viruses, in our search for an effective drug.”

Emory experts also began unraveling the complex properties driving today’s disease transmission — and the speed at which epidemics can travel — while advocating for new methods of surveillance.

Researchers from Emory’s School of Medicine soon collaborated with other US scientists to publish research showing that the Zika virus can infect neural progenitor cells critical for brain development, suggesting a potential explanation for cases of microcephaly seen in Latin America during the Zika outbreak.

In May 2016, scientists and public health leaders from American, Brazilian, and European academic research institutions, global health organizations, government agencies, and the biotech industry gathered at Emory Conference Center for “Bridging the Sciences: Zika Virus.”

Organized by Raymond Schinazi, director of Emory’s Laboratory of Molecular Pharmacology, and the Global Virus Network, the international conference was held to assess current and emerging strategies to minimize the spread and impact of Zika virus infection. Three major areas of research and strategy emerged: mosquito control, geographic reach of the disease, and modes of transmission; the development of therapeutics and vaccines; and prevention of microcephaly and other birth defects.

scientist holding water sample

Transmission and strategies to find immunity

Led by Mehul Suthar, assistant professor of pediatrics at the School of Medicine, and Emory pediatric infectious disease specialist Rana Chakroborty, Emory scientists and graduate students helped pinpoint how the Zika virus can replicate in immune cells from the placenta without killing them — effectively explaining how the virus may pass through the placenta to infect developing fetal brain cells.

“It was known that the virus was getting into the placenta, but little was known about where the virus was replicating and in what cell type,” says Suthar. “Our results substantiate the limited evidence from pathology case reports.”

By last summer, scientists at Emory Vaccine Center were collaborating with investigators from Thailand to discover that people infected with dengue virus develop antibodies that cross-react with the Zika virus and may have the capacity to provide immune protection. In fact, some of those antibodies may have the potential to neutralize the Zika virus, the researchers concluded.

“Zika immune responses and disease severity may be different in dengue-endemic areas, or among dengue-experienced versus dengue-naïve groups,” says Jens Wrammert, assistant professor of pediatrics (infectious diseases) at the School of Medicine and the Emory Vaccine Center. “These factors must be taken into account when doing Zika vaccine or other clinical studies.”

Mulligan in research lab

Progress toward a vaccine

To understand the virus and its host immune response better, Emory researchers also joined a national study of individuals infected with the Zika virus.

Sponsored by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health (NIH), the research sought to help inform the development of future diagnostic tests and possible vaccines for the virus. The study also determined that Zika virus infection is caused by one virus serotype, concluding that vaccination against a single strain of Zika virus should offer sufficient protection against genetically diverse strains of the virus.

“It’s very important to know that infection with Zika virus can produce antibodies that could fight any strain of the virus,” says Mark Mulligan, distinguished professor of medicine (infectious diseases) at the School of Medicine, executive director of the Hope Clinic of the Emory Vaccine Center, and coauthor of the study’s report. “This result is encouraging and helpful in understanding the immune response to the virus and developing an effective Zika vaccine.”

By midyear, research toward the development of a vaccine was gathering momentum. The Hope Clinic was named one of three US sites to test a new NIH-developed vaccine intended to prevent the Zika virus infection. The Phase I clinical trial was launched to evaluate the experimental vaccine’s safety and ability to generate an immune system response.

Audrey Lenhart in lab

Vector control and surveillance

In October 2016, the Rollins School of Public Health’s Hubert Department of Global Health was awarded $850,000 from the CDC to support cross-collaborative Zika response and training efforts.

Led by Dabney Evans, assistant professor of global health, the team will focus on vector control for Zika aimed at increasing the capacity for response in 37 Latin American and Caribbean countries.

Later that month, Emory College’s Environmental Sciences Department also received $1 million from the National Science Foundation and the CDC to enhance Zika mosquito surveillance and contain virus transmission.

“Two years ago the global health community faced Ebola, and Emory was on the forefront of that very important work,” says Evans. “This year we are again at the forefront of the Zika response through our capacity-building efforts.”

Amid reports of mosquito-borne Zika spreading into some communities in the southern US, Emory scientists offered a county-by-county Zika risk map of the US that could be used to help policy makers decide how best to allocate the funds to fight the spread of the virus.

Having a solid, sustainable surveillance system is at the heart of protecting against transmission and disease, says Kitron.

“If we don’t invest many more resources in surveillance, we are running the risk of missing new diseases until much damage is done and costs skyrocket,” he adds. “An effective surveillance system may not prevent epidemics like Zika and West Nile virus, but it will enable us to be better prepared and react sooner.”

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