In a surprising finding, researchers in the Center for Comparative Medicine and Translational Research (CCMTR) at the College of Veterinary Medicine have discovered that HIV can cause portions of the body’s innate immune system, when stimulated, to actually increase the virus’ replication. The finding could lead to a change in therapeutic strategies for HIV patients.
Dr. Gregg Dean, CVM professor of immunopathology and director of the CCMTR, led the research team. Dr. Shila Nordone, a research assistant professor in Dr. Dean’s lab, collaborated on the study, which was published in the journal AIDS Research and Human Retroviruses.
There are two “arms” to the human immune system: adaptive and innate. The adaptive immune system can be “trained” to recognize a particular pathogen by either experience or vaccination – it identifies and responds to specific threats, such as certain strains of flu.
The innate immune system, on the other hand, is designed to recognize broad categories of pathogens – such as viruses, bacteria, or fungi – and to respond when these pathogens invade the body. Specialized molecules known as Toll-like receptors (TLRs) act as the body’s alarm system, and send the signal to produce antibodies when triggered by a particular pathogen. Scientists have identified and numbered TLRs according to the type of pathogens to which they respond.
Dr. Dean and his team looked at certain toll receptors to determine how HIV affected their function. They discovered that HIV impairs the function of a specific TLR, which might explain why AIDS patients suffer from recurrent bacterial infections. The researchers also found that the virus exploited the toll receptors so that when they signaled the immune system to respond to a threat, it resulted in the production of more HIV.
“This goes to a long-standing question about HIV and its interaction with the immune system – does it shut down the toll receptor’s ability to recognize pathogens, resulting in a patient contracting more illnesses, or does it ‘hijack’ the toll receptor, and cause it to replicate the HIV virus?” Dr. Dean says. “We found that the answer wasn’t necessarily one or the other, but that both scenarios can and do occur. On the one hand, the HIV can inhibit toll receptor function, but on the other, stimulation of the toll receptor can activate HIV replication.”
The team’s findings have implications for HIV patients’ treatment strategies.
"A lot of research has focused on getting the human immune system to respond better to the HIV virus,” Dr. Dean says. “Our findings indicate that we want to be careful about utilizing drugs that stimulate the activation of TLRs, because we may accidentally stimulate viral replication.”
— Tracey Peake, NC State University News Bureau
About the Center for Comparative Medicine and Translational Research
The mission of the CCMTR is to enhance collaborative, translational, interdisciplinary approaches for the comparative study of animal and human diseases. The CCMTR involves more than 100 researchers from five NC State colleges and the CVM Veterinary Teaching Hospital. The work of the Center is organized around innovation, translation, and utilization initiatives. Innovation focuses on research collaborations among clinical and bench researchers that will lead to translation and testing through clinical trials. The utilization component seeks partnerships with private industries to develop new medicines, treatments, and biomedical devices for the benefit of veterinary and human medicine.
Posted April 18, 2008