’)ITHP exclusive interview with Edward M. Campbell
August 24th 2010
Edward M. Campbell Ph.D. is an assistant professor at the Department of Microbiology and Immunology at Loyola University, Stritch School of Medicine. ITHP.org got the oppurtunity to interview Dr. Campbell about his breaking research regarding his recent findings on HIV-1 infection
Please share a little background about yourself. How long have you been involved in studying HIV? Who are your collegues? Where does your funding come from?
I have been studying the molecular biology of HIV-1 for around 10 years, during my PhD research and post-doctoral research. I started working on TRIM5alpha during my post-doc at Northwestern. Some of my colleagues from that experience were on the paper that caught your interest. We are currently collaborating with numerous labs, including ones at Rush University, Albert Einstein, NIH and the University of Geneva in Switzerland. My funding presently comes from NIH and Loyola University.
I've read that you have successfully identified the key components of a protein called TRIM5a that destroys HIV in rhesus monkeys? Is this true? *Have you successfully cured these monkeys*?
Our study did not involve rhesus macaques, we merely cloned the gene from these animals that inhibits HIV-1 infection and expressed it in human cells. However, from your question, an interesting side note on the original discovery of the TRIM5alpha proteins is that, many years ago, when other scientists were trying to develop monkey models of HIV-1 infection to study disease progression, they noticed that they could infect some monkeys and not others. Since they were looking for monkeys that could get infected, they went with the ones that did get infected. Rhesus macaques were one of the species that they could not infect, and it took years to figure out why. The answer ended up being that their version of TRIM5alpha stopped the virus cold.
I've read that other researches had already known about this protein. How has your findings further advanced their research?
We certainly didnt discover TRIM5alpha, Matt Stremlau and Joseph Sodroski at Harvard did. Since they discovered it, everyone has been racing to figure out how it works. Right after the virus fuses with the target cell, TRIM5alpha puts a serious and somewhat mysterious whammy on the virus. Before anyone can design drugs that mimic TRIM5alpha, the nature of "the whammy" must be understood. Our study essentially found that once TRIM5alpha binds a viral capsid, regions of the protein recruit other TRIM5alpha proteins to the location, ultimately creating a large assembly that envelops the virus.
Do you believe you have found the cure for humans?
That would be a stretch. We have certainly taken a step towards understanding how TRIM5alpha inhibits HIV-1 infection. As gene therapy applications move forward, we have identified components of the protein that might be exploited to make a more effective inhibitor of the virus.
If so, how long do we have to wait?
Once gene therapy becomes mainstream, and it is making great strides, we can express the version of TRIM5alpha from macaques in human T cells, which would then likely be very resistant to infection. It is also likely that if the virus mutates around the rhesus macaque protein, it would become susceptible to inhibition by the human version already expressed in cells.
Has a cure ever been developed for HIV in the past?
Cure is a big word, there are a number of treatments for HIV-1, including HAART, that inhibit viral replication but do not eliminate it from the host. Perhaps the best new thing going that I have seen is from Paula Cannon at USC, who is using gene therapy to knockout a critical receptor for HIV in the cells of patients (called CCR5). People that dont have this receptor are cannot get infected with HIV-1, and an HIV-1 positive patient that received a blood stem cells from a donor that lacked this protein now has no detectable levels of HIV-1. If she can get that to work, we might all have to find another line of work. Its hard rooting for someone to make you find another line of work, but in this case, I make an exception.
Large media conglomerates need money and readers in order to survive. This story is buzzing all over the web on smaller blogs. Why in the world is this not on the front page of every major newspaper?
I appreciate the interest, we are very happy about our findings. I think for front page material, though, you really need to cure the disease in humans. Our study involved infecting cultures human cells. It is more "basic science" of the type that is not easily digested by the mainstream public.
Is there any powerful people in the world who for some reason would want to suppress a cure for HIV?
Not that I can imagine.
Would a cheap and speedy HIV cure actually cause some drug companies to lose revenue?
I sense this question and the last as stemming from the commonly held believe that there actually is a cure for HIV-1 but it is suppressed for the profits of big pharma. While I cant say what is true of big pharma, the largest problem with the conspiracy theory is the number of people involved and our collective personality types. There are hundreds of academic investigators like myself all working very hard to push the science of HIV-1 forward. Moreover, the vast majority of us are...lets just say somewhat competitive... to say the least. I am friends with many of my competitors, but ultimately we are all striving to beat each other to the next finding, the next paper, the next step forward. It is what makes us tick (and to a certain degree, sick, if you ask my wife). There is simply no way you could convince that many people like that not to shout from the mountaintops
How has HIV attacked parts of Africa so harshly? In America having unprotected sex is extremely common. Is there a more lethal strain spreading? No one has ever provided a logical explanation for this. Black men and woman are also at the highest risk in the U.S. Are they more susceptible?
Africa is the hardest hit mostly because of a lack of access to medical care and education, both of which are critical aspects of HIV-1 prevention. These factors are also responsible for the spread of HIV-1 in some American populations, such as African Americans. They are not more susceptible, but rather they are statistically more likely to come from socioeconomic conditions in which their access to health care and education about HIV-1 is limited relative to the rest of the population. It is critically important to provide funding to educate and treat these populations. If African Americans had the same access to these preventive measures, there is no data that I am aware of that suggests they are more susceptible to infection or subsequent pathogenesis/AIDS progression.
Do you have the authority to test a potential cure on a willing HIV positive participant?
My job is to understand how things work at the molecular level so other scientists can exploit this knowledge for treatment. It is not inconceivable that I could be involved in work like that at some point, but currently our focus is understanding HIV-1 infection and how to combat it. Short answer : no.
Where do you see HIV in 20 years?
With the assumption that gene therapy reaches is promise in 20 years, HIV-1 will likely not represent the public health threat it currently does. If we do our job right, our understanding of HIV will allow us to use the HIV-1 backbone as a gene therapy agent that can deliver genes to target cells in patients, preventing and curing all kinds of genetic and other diseases. However, since I am relatively young investigator (I have only had my own lab for 2 years, researching HIV for 10), I have not been doing this long enough to have my level of optimism vanquished. Perhaps ask someone with more experience.