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M. Christine Zink
Chris Zink and her agility
Chris Zink of
Molecular and Comparative Pathobiology
on being a veterinarian HIV researcher:
What is the role of vets in research?
ZINK: Veterinarians are situated in all medical schools, in industry, in government laboratories and in veterinary schools. Probably the most important role that veterinarians play in research is in the development of animal models to study human disease and devise new therapeutics. Hopkins alone has tens of thousands of rodents that help us with the detective work of understanding disease from molecules to cells to what happens in the whole organism. Most of the veterinary faculty at Hopkins have grant funding and perform independent research on disease pathogenesis. In addition, veterinarians in our department take care of the health of all the research animals at Johns Hopkins.
How does one study HIV?
ZINK: Studying human cells in a dish infected with HIV has told us a lot about the virus, but hasn’t taught us how HIV can affect the body. The virus profoundly suppresses the immune system and this, in turn, impacts the entire body. The closest relative to HIV is the simian immunodeficiency virus (SIV), which infects many species of monkeys throughout Africa. We investigate SIV in macaques as a model for studying HIV infection.
How are SIV and HIV related?
ZINK: SIV has similar proteins and infects cells the same way as HIV. It is believed that HIV evolved from SIV; the theory is that SIV was transmitted from chimpanzees to humans in Africa in the 1920s or 1930s, creating HIV, which can develop into the disease we now know as AIDS—acquired immune deficiency syndrome.
HIV is a worldwide pandemic that infects and kills many people. Why don’t we hear about SIV wreaking havoc on wild monkey populations?
ZINK: SIV has co-evolved with African primates for many millennia and the virus and host have adapted to each other. As a result, African primates usually don’t become ill when they are infected. It’s never beneficial for the virus to kill its host because that gets rid of the virus itself. But, once SIV was transmitted into humans—an abnormal host that had not developed a natural way to combat the virus—it caused people to become really ill.
When African primate viruses infect primates from other parts of the world, like India, they also succumb to disease since they are not the normal hosts. Infecting abnormal hosts with SIV allows us to study the effects of HIV on the body in a laboratory setting.
What specific effects of HIV do you study?
ZINK: We predominantly study the damaging effects of HIV on the brain. HIV causes neurological problems with memory, understanding and motor movements, a condition of clinical symptoms known as HIV-associated neurological disease (HAND). Antiretroviral drugs don’t completely prevent neurological damage because many of the drugs don’t get into the brain.
It’s not only the virus that damages the brain, but also the inflammatory response to the virus that causes the neurological damage. The virus causes inflammation, which stimulates cells from the immune system to come into the brain and secrete small molecule chemokines and cytokines that are toxic to cells. Inflammation in the brain is always a bad thing.
Are there any treatments available for HAND?
ZINK: This is an area of active investigation between us and our collaborators in the Department of Neurology who focus on the discovery of drugs to ameliorate the effects of HIV on the neurological system. We are testing a number of promising compounds in the SIV model prior to initiating clinical trials. Some of these are existing compounds that were tested and recognized to potentially be protective to the brain. Other compounds were discovered by outside investigators who have asked us to test their drugs in our SIV model.
What else do you study?
ZINK: We are using our SIV model to determine the optimal time point to start the HIV treatment regimen HAART—highly active antiretroviral therapy. Because of the high cost and many side effects, patients sometimes do not start on HAART until they demonstrate a declining immune system, signs that the HIV infection is progressing. Up until patients start treatment, HIV inflicts a lot of irreversible damage on the body’s immune system, brain and other organs that the patients may not be immediately aware of, but that could be prevented. We are investigating how early is early enough to start treatment to prevent damage in the body or if there is a risk in treating people too early, with the result that the body is not allowed to make its own natural immune response against the virus.
--Interviewed by Vanessa McMains
M. Christine Zink on finding treatments for HIV dementia: