Fire with Fire, Virus with Virus

Antibodies from Patients with Dengue Virus Could Help Prevent Zika Infections
August 8, 2016

Mosquitos are responsible for some of the nastiest diseases on the planet: malaria, West Nile Virus, chikungunya and more. 

Most recently, the Zika virus is the mosquito-transmitted disease that has been grabbing headlines. Ever since Zika arrived in the Western Hemisphere, doctors have been searching for a vaccine or a treatment to prevent the devastating birth defects the virus causes. So far, nothing.

Zika VirusNow new research from the UNC Schools of Medicine and Public Health, however, has shown that the attack of another virus, Dengue, might provide protection from Zika.

UNC medicine professor Aravinda de Silva and epidemiologist Ralph Baric found that antibodies to the Dengue virus—antibodies the body creates after a Dengue infection to fight off future infections—also have some limited ability to fight the Zika virus. They published their results in the journal mBio.

Dengue and Zika both come from a family of viruses called flaviviruses, otherwise known as viral hemorrhagic fevers, along with West Nile, yellow fever and half a dozen other mosquito and tick-borne illnesses

Flaviviruses, like many viruses have an outer protein shell called a capsid and those capsids have small molecules sticking off of them to recognize and attach to the cells they want to infect. The more closely related two viruses are, the more alike their capsids and molecules sticking off them are likely to be.

A family resemblance may not seem that important—what does it matter what the virus looks like if it causes deadly fever or birth defects? That resemblance is extremely important, however, to the immune system. 

The immune system has two major arms: the innate immune system and the adaptive immune system. The innate immune system is a blunt instrument, devouring or poisoning anything it recognizes as foreign. This system is fast, but not incredibly nuanced.

The adaptive immune system is smarter, more surgical. The adaptive immune system is trained to recognize specific invaders in the bloodstream and kill them. The first time a specific virus or bacteria infects the body, the T-cells and B-cells of the adaptive immune system learn to recognize that invader and kill it.CapsidThe fascinating part is that those T-cells and B-cells remember what the invaders look like. The immune cells pick up on the invaders’ specific molecular signatures, called epitopes, so if the same invader comes back a second time, presenting the same epitope, the adaptive immune cells can quickly jump into action and kill it before it becomes a problem. It’s the reason why vaccines can prevent us from getting diseases and why people generally only get chickenpox once. The immune system gets conditioned and anything presenting those epitopes gets killed before it can multiply into a dangerous infection.

Getting back to Dengue and Zika’s family resemblance, the adaptive immune system can sometimes attack two things with similar epitopes, and not only are Dengue and Zika in the same family, but among flaviviruses, Dengue and Zika are more closely related to each other than to any other flaviviruses. 

Dengue virus

They are so closely related, in fact, that Baric and de Silva found they actually share epitopes. They isolated immune cells and antibodies from people who had been infected with Dengue once or multiple times—Dengue has four forms so the immune system doesn’t automatically recognize all four of them after infection by one form, so someone can get Dengue multiple times—and tested to see whether the antibodies their immune systems made could also protect against Zika.

They found that some of the Dengue antibodies were able to actually fight off the Zika virus both in test tube cell cultures and in mice. The problem is that only 27% percent of the Dengue antibodies had any effect on the Zika and only one third of those antibodies gave a moderate-to-high-level of protection against Zika. 

While the Dengue antibodies are not a miracle cure for Zika, they offer a promising start toward a vaccine for a disease that the World Health Organization estimates is in more than 60 countries and has cases popping up in the United States.

Scientists at UNC will continue to work on treatments and vaccines for both Dengue and Zika in the future.

—Daniel Lane

Daniel Lane covers science, medicine, engineering and the environment in North Carolina.