Indira Mysorekar, PhD, an associate professor of obstetrics and gynecology and associate director of the Centre for Reproductive Health Sciences at Washington University in St. Louis, talks about new research in the fight against Zika.
Interview conducted by Ivanhoe Broadcast News in March 2017.
I want to talk a little bit about Zika. Everyone has heard about Zika and it’s been a little bit quiet but do you anticipate that we’ll start hearing more about this virus again in the United States in the coming months?
Mysorekar: Yes I think so. Obviously one never knows for sure but with the coming summer heat and activity of the mosquito that carries the virus we probably will be seeing more cases.
This will be back in the public eye again in the United States and the research has never gone away.
Mysorekar: It’s never gone away for us because first of all, in pregnancy we don’t typically have many infections that cross the placenta from the mom to the baby. It’s in a way a great miracle because the moms could be infected with any number of things. But the placenta which is the tissue inside the mother’s uterus that takes care of the baby all through pregnancy is a very strong barrier. It really can handle a lot of bacteria or viruses, parasites. There’s only a few that have been able to cross over, we hear about rubella, the German measles, there’s cytomeglo virus that can cross over and sometimes you have cases of listeriosis. But till Zika came by the only other major virus that we had that would do this is HIV. Zika really has turned a lot of our understanding on its head that this virus can enter the moms system and not really affect the mom particularly any more than a normal adult with a little fever, some joint pain, some conjunctivitis. But if she is pregnant especially early in pregnancy the first trimester, early second trimester if she gets infected then the chances of the baby having really bad things happen to it are very high.
Do researchers know yet why this virus is able to cross the placenta?
Mysorekar: Some answers are coming and there’s been a tremendous investment of the research community in to understanding and dealing with this problem which has really been tremendous effort and a lot of people working together which has been really great.
Do researchers have an understanding as to why this virus crosses the placenta?
Mysorekar: Yes, new research is now coming out that suggests that it’s showing that there may be some progress. Zika is a virus that has what’s called envelope basically just like a letter with an envelope around it. That envelope is made up of proteins that are important for the virus to be able to do its viral activity. Some of these proteins can be targeted. What I mean by that is that some of these proteins appear to be involved in being able to overcome the normal barriers and be able to cross the placenta. For example we had a study that was published a couple of months ago showing that if we have an antibody which basically can attack and bind the virus then the virus can’t cross over. Maybe one of the reasons it works is because we’re able to block that protein from doing it’s function. As more studies come out we’ll understand more and more from the virus side of things how the virus is able to cross over. New research including from our lab and our group is looking into how is the virus able to overcome the normal barrier, which are as I mentioned earlier really tremendous. Somehow the virus is able to use it or block it or overcome it to cross the placenta. So those are new things that are ongoing.
If you could speak a little bit to the work that is going on here in your lab and here at Washington University.
Mysorekar: Certainly. WU has definitely been at the very forefront of research on Zika and that’s been thanks to Mike Diamond who’s a virus expert here at WU and an Infectious Disease physician. He has had a lot of interest in emerging viruses which means new viruses that you know you don’t hear about and suddenly they’re in the public eye and it’s an epidemic. He started working on Zika in 2015, a lot earlier than other people because he had heard about what was going on in Brazil and that there were new things happening in pregnant women and there was this new virus. He started to set about figuring out how to study this virus. To study how the virus does it thing we like to develop animal models so we can look at the process and so on. There’s a problem in that these viruses affect humans and non-human primates like monkeys. They typically don’t infect kind of the animal models we look at which is small mice. He generated mice that could get infected by the human virus and be able to have the process that was happening in humans. That’s where he was at when I got together with him and I study as I mentioned, infections in pregnancy. It’s been a long standing interest of my group and we have a lot of expertise in studying the placenta and cells of the placenta and how they basically handle infections and the reaction to infection. We made these mice that could get infected, pregnant and we gave them an injection, subcutaneous to resemble a mosquito bite basically and giving as many viruses as would enter a women if she was bitten by a mosquito carrying the virus. We had pregnant mice that were bitten by this virus, bitten by the mosquito with the virus and then we looked at what happened during the course of pregnancy. The thing that we found was just shocking, was that most of the fetuses were dead (so a mouse can carry up to ten to twelve fetuses). One point I wanted to make we started off by talking about our animal models but I went on to talk about babies in humans. That’s because a lot of the events that we saw in the mouse fetus and fetal development and brain development and defects because of infection were pretty identical to what we were seeing in people. That was really good because now we had an animal model that worked and we were able to study the different events. Now we can expand that even further to ask the next question which is basically can we then stop it, now that we know it is going across can we stop it and again this is still at the level of our animal model. Dr. Diamond that I mentioned earlier has set up collaboration with James Crow who is the Director of the Vaccine Center, of the human vaccine development center ad Vanderbilt. Dr. Crow’s center gets blood samples from the CDC from any patient who has been positive for Zika. He screens those blood samples for any of these antibodies. When you get a viral infection you can develop antibodies. He identified antibodies that might be able to bind or bind meaning attach to the envelope proteins of the virus that I was mentioning. It was the idea that if that antibody binds to the envelope essentially then you grab the virus and don’t let the virus do its thing. Then doing the screen we identified several antibodies that were working very well to block this envelope protein. We put one of those an antibody called H117 in to our animal model and we were absolutely gratified to find that the treatment with antibody either a day before infection with the virus or a day after infection. Both prophylactically as well as therapeutically the virus was blocked at the outer wall. Remember I mentioned all the different layers of walls around the baby and then the outer most wall is the mom’s uterus and uterine area and that’s where the virus was blocked. It just was not allowed to cross over in to the placenta in to the area where the blood flow and nutrient and oxygen exchange happening and so the babies were fine. They were born normal, they had no viruses in their brain, and they had no brain defect. That was extremely gratifying.
How likely is it that you can take it one step further from mouse model to human model?
Mysorekar: That’s what we are working on now. This is again out of my hands now this is going in to human trials but the first round of trials are starting now with this antibody. That was from our group but there are other groups that are also generating antibodies and others are generating vaccines and some of these vaccines are going in to the early clinical trials.
How gratifying is it for you to see this work going so quickly. Sometimes it takes years and years of this kind of research.
Mysorekar: That has been one of the most terrific and greatest scientific experiences of my life. Because we typically are used to slugging away for years and a question and it takes thousands of researchers often and thousands of man hours to then end up with a drug that helps people. We generate knowledge that together goes forward and as a patient you go to the clinic with a problem and there’s a prescription you can get to fix that problem. We’re used to that we’re used to you know looking at the early studies that eventually will lead to something. This has been absolutely terrific. I started working on this project, this virus just about a year ago. We started at the beginning of February; it’s not even a year. We’ve learned so much and we’ve come up with a method to block the virus. Our new studies are now focusing on what happens inside the placental cells, like what does the virus do, how is it able to multiply inside the cells and what is it that it’s actually doing. Now we can go deeper in to understanding the methods it’s using. This is terrific because studies of the placenta, studies of pregnancy are all things that are typically not particularly supported by funding and so the knowledge is limited. The idea as well, women give birth all the time it’s no big deal. The placenta is just an extraordinary organ and we’re learning more and more about nutrition during pregnancy, stress during pregnancy and infections during pregnancy that can have lifelong effects on the human being even in to adulthood. Obesity and diabetes a lot of these adult conditions often now are known to have their root back in what happened when we were inside our moms. This has been great because this virus you know it’s a terrible thing but it’s allowed us to look inside this tissue and basically shine light on this tissue so we can study more. Now we can use these models to understand other pathogens which are bad guys, bad bugs, other viruses, bacteria, parasites that can cause infections in pregnancy.
Is there anything I didn’t ask you that you would want people to know about the research?
Mysorekar: Yes, I think one point that I like to make is that because this virus kind of burst upon us you know in terms of attention and then people expect many things and to continue and then it seems like oh, maybe there are fewer cases, we started with that question in the beginning. Maybe it’s tapering off and maybe it’s over and so on. But what I feel really feel is very important even if we were able to curtail the mosquitoes or block the virus in some cases the way it has been able to overcome defenses and I know that you will be talking with my colleague who has also shown the Zika virus affects not only pregnant women but also male testes. That can affect any man. As a man or a boy you may just have some cold like symptoms. You may not know that the virus has caused a lot of damage in the testes until you decide maybe to have children so it may be years later. We don’t know what the long term effects are. We don’t know what the long terms effects on babies brains are. We know there’s been damage and what are all of the consequents of that damage? I think that in that sense it’s not over at all. I think we’re just scratching the surface. Because even hopefully there won’t be any new cases but even with the cases, even the thousands of cases that have been in the United States and worldwide dealing with the aftermath of that is already quite considerable. I think that I would say that it’s still important and critical to continue doing research, continue investigation methods of blocking this virus or other viruses that may come after this. And then being able to understand how it’s able to do what it does.
END OF INTERVIEW
This information is intended for additional research purposes only. It is not to be used as a prescription or advice from Ivanhoe Broadcast News, Inc. or any medical professional interviewed. Ivanhoe Broadcast News, Inc. assumes no responsibility for the depth or accuracy of physician statements. Procedures or medicines apply to different people and medical factors; always consult your physician on medical matters.
If you would like more information, please contact:
Diane Williams
314-286-0111
Sign up for a free weekly e-mail on Medical Breakthroughs called First to Know by clicking here.
