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Battling Ebola: How Ebola Kills

MED’s John Connor is devising diagnostics to spot Ebola and antivirals to treat the disease

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On Saturday, the first of two sickened American health care workers was flown from Africa to a special containment unit at Emory University. Despite the risk of infection, medical personnel continue to travel to West Africa to help bring under control the worst Ebola outbreak on record, which has killed more than 900 people to date. The World Health Organization plans to spend $100 million to fight the outbreak, and the Centers for Disease Control and Prevention will send 50 more aid workers. In this weeklong Special Report, BU Today talks to Boston University researchers in several fields about why medical personnel confront the risks; the ethical and political dilemmas presented by the outbreak; how the virus kills; efforts to design effective therapies; and other aspects of this unprecedented outbreak of Ebola.

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John Connor, a researcher at BU’s National Emerging Infectious Diseases Laboratories (NEIDL), says the immune system’s response to Ebola is “totally out of whack” compared with its responses to other viruses. Photo by Kalman Zabarsky

The Ebola outbreak in Guinea, Sierra Leone, and Liberia has now infected more than 1,600 people, according to the World Health Organization. To learn about how the virus kills and efforts being made at BU to devise diagnostics and therapies to treat it, BU Today spoke with John Connor, associate professor of microbiology at the School of Medicine and a researcher at Boston University’s National Emerging Infectious Diseases Laboratories (NEIDL). Connor, whose research is funded by the National Institute of Allergy and Infectious Diseases, studies the tricks that viruses use to dominate their cellular hosts. He has been working collaboratively with researchers at BU and at other research institutions, with a particular focus on the Ebola virus.

BU Today: What aspect of the Ebola virus is the focus of your work?

Connor: My lab is interested in several different approaches to try to understand and stop diseases caused by viruses like Ebola. This includes the development of antivirals, vaccines, and point-of-care diagnostics, in collaboration with the Photonics Center and the lab of Selim Unlu, College of Engineering associate dean for research and graduate programs in the department of computer and electrical engineering.

Another thing we are looking at is what goes wrong with the immune response during viral infection. Our bodies are so good at responding to so many diseases, and in most cases we get sick for a couple of days and then we get better. Our response to Ebola is totally out of whack. The immune system appears to deliver a much more aggressive response than is necessary, one that causes a lot of damage to the body. That overreaction is a significant part of what makes infection with this virus so deadly.

What kind of damage is done by the overreaction?

The response is so strong that it triggers other pathologies. This can include diffuse intravascular coagulopathy, which is why the virus is often called a hemorrhagic fever virus. Normally, coagulation is constantly serving your body, so if you get cut you get a nice blood clot that seals you up. It’s a great way to keep your blood from leaking out. In the case of Ebola, you get clotting in inappropriate places, such as organs like the liver. The problem is, you have a finite number of clotting factors in your body, and they get depleted from the inappropriate clotting. When that happens, you have a hole in your body that needs clotting but won’t stop bleeding. All the small things that happen on a daily basis that are normally taken care of by coagulation are not working.

Do other viruses cause the same coagulation problems?

Ebola is one of the viruses that are most associated with that type of response. The Marburg virus, a cousin of Ebola, can also cause that response, and Lassa fever viruses can as well. Dengue virus can also cause a hemorrhagic disease, in rare cases.

Does every victim of Ebola hemorrhage?

No, but it happens a lot of the time, whereas in other viral infection such as the common flu, it does not happen.

Why is it that some people infected by Ebola get much sicker than others?

That’s one of the things we are trying to learn, but it’s hard. One of the problems of studying a virus like this is that you don’t have large pools of people to work with. Outbreaks of Ebola are sporadic. If you are studying HIV/AIDS, the prevalence of the disease means that you can readily identify 10,000 people. Ebola outbreaks are not predictable and, thankfully, most previous outbreaks were small. This makes other approaches to understanding the course of disease important to try. We are now collaborating with people at other labs who are using animal models of the disease.

What are you learning about how the virus works?

One of the things we’ve been surprised by is how early the immune system response begins and how robust it is. When we compare this response to other viruses, it appears that the response to Ebola is much stronger than to other types of disease. Also, it appears that specific types of responses are associated with survival from the disease. We are investigating whether this early immune response can be used to develop a diagnostic for early disease. Can we look very early, even before symptoms show up, and identify an immune system response to an Ebola infection?

How is the immune response of survivors different from that of people who die?

We have learned that it’s not just the intensity of the response. It also appears to be the type of responses that develop. One of the things we see in animals that succumb to the disease is one type of immune cell—a type of neutrophil—accumulates, whereas in animals that survive, that immune cell is not as abundant.

Are there any therapies that are effective?

There are no Food and Drug Administration–approved therapies. People are beginning to develop some therapies, and information from those studies says that the earlier an individual is treated, the better their survival.

If we can find ways to diagnose infection early, that will directly help effective therapy. And with early diagnosis, if you identify one patient that is symptomatic, suggesting that their course of disease is far along, early tests like the one we are developing will allow rapid testing of contacts of that first patient and early treatment of those infected with the disease.

We are really trying to understand what this very overactive immune response is and how we can start damping it down. Our lab is also developing antivirals that work against Ebola, and we are working on diagnostics that will be at the point of care. We have been focusing on developing a diagnostic for Ebola, Marburg, and Lassa, where point of care is a high priority. We are doing this with the Unlu laboratory at BU, with collaboration from BD Technologies and a spin-out company, NeXGen Arrays, which was started by BU alums and is primarily interested in developing these assays. We are also developing second-generation vaccine viruses in collaboration with Tom Geisbert, former associate director of the NEIDL. The collaboration started when Tom was at BU and has continued since his move to the University of Texas Medical Branch.

Tomorrow: Tracking the Ebola virus. Read all stories in our series “Battling Ebola” here.

6 Comments
Art Jahnke

Art Jahnke can be reached at jahnke@bu.edu.

6 Comments on Battling Ebola: How Ebola Kills

  • Knox Pruett on 08.06.2014 at 12:02 pm

    Hello Doc,
    Since Eboli causes the human immune system to over react, and is usually fatal. Why not treat a virus with a virus? Give the patient HIV/AIDS to stop the body’s reaction, then treat the HIV. May buy some time.

    Just my thoughts,
    Knox Pruett
    Austin, Texas 78749

  • John Connor on 08.06.2014 at 12:54 pm

    Hello Mr. Pruett,
    I do not and would not advocate intentionally infecting anyone with HIV. I see the line of your reasoning, but I think that two virus infections would be worse than one. I do agree with your idea that it would be a good to try to “quiet down” the immune response (but not turn it off). It would be interesting to study how to do this effectively.

  • Andy Rodgerson on 08.07.2014 at 5:56 am

    I would like to know a little more about both the clotting and other immune responses.

    For instance, would anticoagulants in the early stage prevent inappropriate clotting in the liver? And would infusion of clotting agents such as prothrombin complex be of use later on, when the clotting agents are exhausted?

    Secondly, are there any similarities with the “cytokine storm” associated with the spanish flu virus? I have read that in that situation, medications as simple as aspririn and Omega-3 oils have been proposed to moderate the immune response so that the cytokine storm does not kill the patient.

    I would be interested to know if there are any similar sensible precautions I could take with over the counter supplements in the case of Ebola.

  • Laura Lediaev on 09.17.2014 at 7:30 pm

    Would administering extreme doses of vitamin D3 help to control the overreaction of the immune system?

  • Jeff Colonnesi on 09.30.2014 at 7:02 pm

    If the immune sytems overreaction is the most damaging aspect, wouldn’t immunosuppressants (such as are used for transplant patients) be of use?

  • Dedy on 10.17.2014 at 2:29 am

    Has the first patient to become sick in this outbreak, know as “patient zero” been identified?

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