The Zika virus lingers in the saliva, sex organs, and nervous systems of monkeys long after the infection is gone from the blood, new research shows. This means that certain organs might harbor the virus even after the immune system has beaten it back, extending the risk that Zika might be spread. And if the virus infects adult human brains as well, it could mean that Zika might be causing more neurological issues than we realized.

"Every study that gets done is filling in pieces of this puzzle."

The study, published today in the journal Nature Medicine, shows that there’s still a lot we don’t know about the virus that has infected thousands of people, including more than 50 who contracted Zika in the continental US. Scientists are still scrambling to find a vaccine.

The mosquito-borne Zika virus came to worldwide attention in late 2015 when it was linked to hundreds of babies born in South America with abnormally small heads — a condition called microcephaly. Since then, we’ve learned that Zika can cause a variety of brain defects in babies born to infected mothers. And while Zika virus infection in adults is usually so mild that most people don’t even notice symptoms, it can sometimes cause a rare and potentially fatal neurological disorder called Guillain-Barré syndrome.

Researchers are still trying to figure out which tissues Zika infects, how it spreads through the body, and how the immune system fights off the infection. All this information is key to developing a treatment or vaccine.

"There’s a real urgency right now to learn about Zika virus, and we’re still at an early enough stage that what we don’t know is more than what we do know," says David O’Connor, a pathologist at the University of Wisconsin who wasn’t involved in the research.

"What we don’t know is more than what we do know."

In today’s study, scientists led by James Whitney, a virologist at Harvard University, infected 36 macaques with two different strains of Zika, one from Thailand and one from Puerto Rico. After the researchers injected the virus right under the skin of the monkeys — just like a mosquito would — they tracked how it spread. They saw that the virus hitched a ride on immune cells to a nearby lump of immune tissue called a lymph node (the same swellings you can feel under your jaw when you have a bad cold). Then, the virus multiplied and spread throughout the network of lymph nodes where immune cells replicate.

The researchers noticed that five to eight days after infection, the monkeys had mounted enough of an immune response to clear the virus from their bloodstream. Three weeks after the virus was gone from the blood, small amounts were still detectable in the saliva of about half of the monkeys. Zika also persisted in the male testes, prostate, and semen, as well as in the uterus and the fluid that bathes the brain and spine, called cerebrospinal fluid or CSF. When the researchers looked at the brains of a few of the monkeys about one week into infection, they discovered that Zika had infected the neurons of a brain region called the cerebellum, which helps coordinate movements.

"It’s going to take a significant amount of additional work to unravel."

"It’s interesting to realize that during an infection the virus could be getting into the brains of adults who are otherwise healthy," says O’Connor. "It’s going to take a significant amount of additional work to unravel what that really means."

We already knew that the Zika virus is present in people’s saliva for about two weeks after infection. But if it turns out to linger even longer and in several organs, it could mean infected people are contagious longer. The fact that the Zika virus manages to infect the brains of otherwise healthy monkeys means that in Zika-affected regions when an adult comes down with neurological symptoms without a known cause, clinicians should possibly consider Zika.

Scientists are still scrambling to find a vaccine.

Some questions remain unanswered. How long does the virus persist in the brain? Does it replicate there? How is this related to Guillain-Barré — and what sort of long-term damage could a Zika infection in the brain be causing? Other ongoing, longer-term studies could help answer some of these questions, Whitney says.

One piece of good news is that the monkeys in today’s study who became immune against one strain of Zika virus were also immune against the other strain. That holds promise for the development of a Zika vaccine.

"This is quite reassuring that basically the strains have not diverged enough," says Nikos Vasilakis, a virologist at the University of Texas Medical Branch. If you’re exposed to one, you’re protected against another. Now, we need to test if that holds true for strains that have been evolutionarily separated for some time, like the African and American strains of Zika, Vasilakis says.

Obviously, today’s findings involved monkeys, not humans. But they add to our understanding of Zika in important ways. "Every study that gets done is filling in pieces of this puzzle," O’Connor says.