Vincent Racaniello, PhD, is the Higgins Professor of Microbiology & Immunology at Columbia University Medical Center. He has conducted research on influenza and polio, and now his lab is working on Zika virus. Dr. Racaniello runs a weekly podcast on the science of viruses called “This Week in Virology.” The below comments were edited for clarity.
What research is your lab doing on Zika?
Every week now, there are new papers coming out about Zika virus. I’m amazed at how many virologists have switched to Zika virus. I must say, we are no exception. We’ve got a number of strains of the virus in our laboratory and we’re asking a number of questions.
As scientists have said before, one does not simply walk into the placenta. That’s taken from a cultural meme, “Lord of the Rings.” One does not simply walk into the placenta because the placenta’s surrounded by a layer of cells called trophoblasts, which are very resistant to virus infection. So a virus can’t simply cross the placenta and that’s why most viruses do not get into the developing fetus. Only a handful of them, apparently including Zika.
So, what I’d like to know is how does it do this? We can’t do this in people, obviously, so we have to have an animal model. No one yet has reported an animal model of the virus being able to cross the placenta. That’s one of the things we’re interested in doing. We’d like to take a mouse model and see does the virus cross the placenta. I have a relatively small lab so it’s hard to keep up, but that’s a big question: How it gets into the placenta?
Next, once it does get into the developing fetus, how does it cause microcephaly and other birth defects? What kind of cells is the virus infecting in the fetus? Is it just brain cells? Or is it other cells as well? When it infects them, what is it doing? That’s another question we’re interested in answering here.
What do we know about Zika right now?
Just in the past few months there have been a number of small studies, mostly out of Brazil, which have shown that Zika virus can enter the developing fetus and cause a variety of birth defects. One of the most prominent is microcephaly, where the skull and the brain are smaller than they should be. We think that the virus can get into neural tissue and replicate there and cause problems.
I think the latest is the announcement by the Centers for Disease Control and Prevention that they’re convinced that Zika virus infection is associated with congenital birth defects. The CDC has advised people who are pregnant, or thinking of getting pregnant, not to go to areas of the world where Zika virus is circulating.
There’s also some evidence that the virus might be sexually transmitted, which of course adds another wrinkle to the whole story. We don’t know how significant that transmission is in the overall scheme of things. Certainly mosquitoes are the most responsible for transmitting the virus. It’s spread by Aedes aegypti, Aedes albopictus, and a lot of other mosquitoes as well. Wherever mosquitoes are present and where people are susceptible, which is most of the world at the moment, the virus is going to do very well.
What has scientific research discovered about Zika so far?
I think one of the interesting aspects is that the viruses that have been sequenced so far fall into African and Asian lineages and it’s the Asian lineage that is circulating in Brazil. The question is, of course, is that lineage particularly better at infecting people and spreading than the others? Very hard question to answer but interesting problem.
The structure of the virus has been solved so now we can make gorgeous pictures of this virus, a deadly virus but beautiful, and we can see exactly what it looks like.
Several groups have shown that certain mice can be used as models for infection. Laboratory mice aren’t terribly infectable with the virus, but if you remove parts of their immune system, then you can then infect them. The virus will enter the central nervous system and replicate there. Interestingly, one of the other sites of replication are the testes. That has implications for sexual transmission of the virus as well. Having a mouse model will inform us about basic science, but it can also be used to screen for antivirals and vaccines in the future. We need an animal model in order to do that.
I think the other important finding is that, at least in culture, Zika virus is able to infect cells of neuronal origin, which confirms some of the signs that we’re seeing, both in fetuses and in adults.
Is the United States at risk?
We do have territories of the U.S., like Puerto Rico, the American Virgin Islands, Samoa, and they have already had circulation of Zika virus in mosquitoes on those islands and transmission to people. In the continental U.S., we’ve only had imported cases.
So will Zika virus spread within the U.S.? Now, the mosquitoes that spread the virus are here: Aedes aegypti, Aedes albopictus. They tend to be mainly in the Southern states but the range extends up to New Jersey and parts of New York, and a little bit westward. The question is whether they’re going to be transmitting the virus.
Now, my opinion is based on the following: We have had Dengue virus, and we’ve had Chikungunya virus brought into the country on multiple occasions and there only have been very, very small outbreaks in Texas and in Florida. Those viruses are transmitted by the same mosquitoes. But our lifestyle is somewhat different here. We have screens on most of our windows; we have air conditioning so we stay inside a lot. In many places there’s great population density but I think the opportunities for interacting with mosquitoes are fewer.
Also, Dengue, Chikungunya, and Zika virus are spread from person to person, there are no animal reservoirs in the U.S. West Nile virus, which was very good at spreading through the U.S., is also present in birds and all other animals so a big reservoir builds up of the virus, from which mosquitoes can take and infect humans. Furthermore, West Nile virus is spread by a different mosquito, culicine mosquitoes, which are far more prevalent up here.
My prediction is I don’t think we’re going to have extensive spread of Zika virus in the U.S. but we should be ready for it, in any case.
How much of a threat is Zika?
One of the issues with Zika is that much of the Western hemisphere was susceptible. None of us had been infected before; we didn’t have antibodies to prevent infection, a second infection. That’s why at the moment it’s spreading like crazy through South America and Central America. Lots of people are susceptible and the mosquitoes are everywhere. I have a feeling that after a few years so many people will be infected that the rate of transmission will go down and if we don’t have a vaccine, we’ll likely have cyclical outbreaks, maybe every five or eight years or so.
Now, for most people, the risk of serious disease is really minimal. First of all, only 1 in 5 people who are infected seem to get any kind of disease. The typical Zika disease is a rash, a fever, a little conjunctivitis, joint pain, headaches, and so forth, and very rare fatalities. So, not a serious disease. The problem, of course, is if you are pregnant, you don’t want to be infected because there are apparently threats to the fetus.
Now, having babies born with congenital birth defects is a tragedy. There’s no doubt about that and we don’t want to have them born that way because they have to be cared for their entire lives. But I want to remind everyone that other viruses that we have now in our population are able to cause birth defects as well. Cytomegalovirus, which infects nearly everyone on the planet, is a serious cause of birth defects globally. We don’t have any way to prevent that. Rubella virus used to be a huge cause of birth defects in the U.S. Before a vaccine was introduced in 1969, there were outbreaks of Rubella every five to eight years and they were accompanied by children being born with birth defects at a rate of about 1 in 1,000 live births.
Now we have a vaccine for Rubella; we can prevent congenital rubella syndrome. it’s been eliminated from the U.S., but listen to this: In the rest of the world, there are up to 100,000 babies born every year with birth defects caused by Rubella, which is a vaccine-preventable disease. Why is this? Because we simply don’t immunize everyone who should.
So, put into context, I don’t think Zika is a huge threat to the world’s population. We can take measures to minimize our exposure and minimize the dangers to the prime candidates, the fetuses.
What symptoms are associated with Zika?
Most viral infections do not produce symptoms. There are a few exceptions: One of them is rabies. When you get rabies infection, most people infected have symptoms of rabies. Ebola is probably the same. We’re not actually quite sure, but most people who get infected with Ebola have symptoms. Most other viruses, it’s a fraction of people who have symptoms. With the virus I’ve worked on in my career, Polio virus, only 1 in a 100 people get paralysis. The others may have no symptoms at all, or a mild flu-like illness. So Zika, about 1 in 5 infected people seem to display symptoms, which include the rash and the fever and so forth.
This is a worry, right? Because you could be infected and you wouldn’t know it. Again, if you’re pregnant or thinking about getting pregnant, you wouldn’t even go for health care advice on that, because you wouldn’t know you were infected. So I would that say if you’re in an area where Zika is circulating and you’re early in your pregnancy, or you’re thinking of getting pregnant, you should go have a blood test to see if you have a Zika infection. Right now, we can do some tests to figure out if you’ve been infected. But the real scary part to me is that you could be infected with no symptoms and not know it, and being pregnant and having that status is really dangerous, I think.
How can Zika be controlled?
I think mosquito control is our only option because vaccines and antivirals will take a few years to develop. We were lucky with Ebola in that we’d had a number of vaccines developed and were at the point of being tested in humans, and during the outbreak in West Africa they were immediately put into testing. We don’t have any candidate vaccines for Zika. I’m sure people are working on them at the moment. I’m sure people are working on antivirals and monoclonal antibody therapy, like ZMapp for Ebola virus. Short term though, mosquito control is the most important way that we can prevent infection. If you bring down levels of mosquitoes, you don’t have to eliminate them all, bring them down to a certain level, and you’ll cut infection. If you inform people to try and be sensible and avoid being bitten by mosquitoes, you can do that. Eliminate standing water if you’re living in an area with that and so forth, I think that’s our best short-term solution to this.