M. Christine Zink, DVM, PhD, DACVP

HIV, the agent that causes acquired immunodeficiency (AIDS), is a lentivirus that causes persistent infection, immunosuppression with resultant opportunistic infections and chronic disease including encephalitis and pneumonia in humans.  One of the important characteristics of lentiviruses is their ability to replicate in macrophages; replication in these cells is linked to the development of neurological disease and pneumonia in infected individuals.  We study the SIV/macaque model of HIV infection to understand how HIV causes systemic and tissue-specific diseases. 

We have demonstrated that SIV replication in the brain induces the expression of chemokines, particularly MCP-1, that recruit lymphocytes and macrophages to the tissue.  This influx of cells results in inflammation within the tissue, which may have both beneficial and detrimental effects.  On the one hand, the inflammatory cells may include specific immune cells that can kill virus-infected cells and lower viral load.  On the other hand, some of the inflammatory cells may themselves be infected, resulting in an increase in viral load.  How these two scenarios play out in the tissue probably determines the outcome of infection.

We have recently identified an antibiotic that is inexpensive (patent has expired) and completely safe that suppresses replication of HIV/SIV and significantly suppresses the encephalitis and neurodegeneration associated with HIV/SIV infection. We are currently examining the mechanism by which this exciting drug functions in the CNS.

We also are performing pre-clinical testing of a number of other drugs that have shown neuroprotective activity in high throughput assays, treating SIV-infected macaques with these drugs to ameliorate the effects of SIV replication and the resulting inflammation on the brain.