The Zika Virus's Family Tree

What the disease spreading through the Americas has in common with yellow fever, dengue, and other flaviviruses

A health worker holds a container of Aedes aegypti mosquito larvae at a lab in San Jose, Costa Rica. (Juan Carlos Ulate / Reuters)

In the summer of 1878, the city of Memphis, Tennessee—home to 45,000 to 50,000 people—suddenly became a ghost town. An epidemic was sweeping through the city, causing people’s temperatures to spike, their organs to fail, and their eyes and skin to turn yellow. The first Memphis resident to die from the yellow-fever outbreak did so on August 13; by August 18, nearly 20,000 people had fled. By the end of the epidemic, Memphis contained less than half of its original population.

At the time, germ theory was still a brand-new concept. Doctors had no idea that the cause of yellow fever was a virus 1,000 times smaller than the human eye could detect, and they definitely had no idea that mosquitos were the carriers (although the Cuban doctor and researcher Carlos Finlay guessed in 1881 that the tiny insects were responsible for spreading the disease). It wasn’t until 1927 that researchers isolated the virus, and another 10 years before an effective vaccine would be developed.

The yellow-fever virus that plagued Memphis eventually lent the Latin version of its name (“flavus,” meaning “yellow”) to the group of viruses that share its molecular characteristics. In addition to yellow fever, the flaviviruses include West Nile, dengue, Japanese encephalitis, and Zika, the last of which recently led the World Health Organization (WHO) to declare a global public-health emergency.

Among other shared traits, the flaviviruses spread quickly and easily—a characteristic that the world is now re-learning with the current Zika outbreak. In part, this is because of the way they pass from one species to another. A majority of the flaviviruses are spread by ticks and mosquitos, which in turn can infect humans and other animals, like monkeys and birds; in the Americas, people have mostly contracted Zika through the bites of the Aedes aegypti mosquito.

The flaviviruses’ ability to spread so rapidly is also due in part to the structure of its genetic material. All viruses contain either RNA (short for ribonucleic acid) or DNA; flaviviruses have a single strand of RNA that contains all the information the viruses need in order to make copies of themselves, which also means they mutate more easily. Mistakes in replication can happen in both DNA and RNA, but DNA has more systems in place to proofread and correct mutations that may naturally arise.

“The RNA viruses do not have these correcting mechanisms, so the mutations remain and get passed to the next generation,” explained Isabel Novella, a professor at the University of Toledo who studies the evolution of viruses. In fact, RNA replication has an error rate roughly 10,000 times higher than that of DNA, which means that RNA-based flaviviruses evolve that much quicker.

As Julie Beck recently reported for The Atlantic, Zika virus has been around for a while (the first human case was diagnosed in 1952), but it only caused sporadic human infections until the first major outbreak on the Micronesian island of Yap in 2007. Even then, the symptoms were about as bad as what you’d experience with a mild flu: fever, rash, headaches, and joint and muscle pain. But in an outbreak in Tahiti in 2013 and 2014, a small number of people began showing signs of Guillain-Barré syndrome—a condition that causes the immune system to attack a person’s nerves, resulting in muscle weakness, tingling and even paralysis. In the Americas, pregnant women infected with Zika have also given birth to babies with microcephaly, or smaller-than-normal heads (the virus hasn’t been causally linked to microcephaly, but, as Beck noted, health authorities strongly suspect a connection).

It’s possible that these new symptoms could be a result of the Zika virus’s evolution, said Duane Gubler, a professor of emerging infectious diseases at the Duke-National University of Singapore. “[Zika] was perceived to be a virus that caused only minor illness,” Gubler said. “[Guillain-Barré from Zika] was relatively infrequent and it didn’t cause a lot of concern, but when it moved into the Americas and people started to see babies born with microcephaly, that changes the public-health importance of this virus completely.”

Scott Weaver, a professor at the Institute for Human Infection at the University of Texas, Galveston, said Zika’s rapid spread may also have to do with a mutation that allowed it to better adapt to the Aedes aegypti mosquito. For example, the virus could have become more efficient in replicating within a host human’s blood, making it more likely that a mosquito feeding on an infected person would become infected itself.

Historically, the spread of flaviviruses has been helped along by human travels. A 2014 paper published in the Journal of General Virology postulated that the flaviviruses tagged along with early humans in the first migration out of Africa. Researchers have also used genetic analysis to show that the yellow-fever virus and its Aedes aegypti mosquito carriers most likely came across the Atlantic with the colonial slave trade.

The board of experts assigned by Congress to investigate the 1878 Memphis yellow fever outbreak also made the connection between travel and the spread of infectious diseases. “In its migrations across seas and continents, yellow fever has always followed the lines of human travel and commercial intercourse,” they wrote in 1879.

But the history of flaviviruses also has an optimistic note: Some of them are vaccine-preventable. Besides yellow fever, there are also vaccines for tick-borne encephalitis and Japanese encephalitis. Recently, the White House announced a funding push for Zika-vaccine research; as Nora Kelly reported for The Atlantic earlier this week, officials hope to have a vaccine ready for trials later this year.

And because other flavivirus vaccines already exist, Gruber said, there’s reason to believe that a Zika vaccine is within reach. “Some of [the flavivirus vaccines] have been very successful,” he said. “We have a head start.”