amfAR, The Foundation for AIDS Research

HIV in the Brain

By Jeffrey Laurence, M.D.

Dr. Paula CannonDr. Paula CannonMost studies of the latent HIV reservoir, the primary impediment to a cure, focus on T cells. But amfAR grantee Dr. Paula Cannon, working at the University of Southern California with colleagues there and at Case Western Reserve University, has taken a different approach. She notes that the brain also contains distinct populations of three specialized cells infected with HIV: microglia, astrocytes, and macrophages. She sought to develop a mouse model to study these cells and their role in HIV latency.

Writing in the April issue of the Journal of Neurovirology, Cannon and associates emphasize the difficulty of studying brain cells from HIV-infected humans. In addition, the differences between simian immune deficiency virus and HIV make the monkey a less-than-ideal model for studying HIV in the brain. Instead, she used “humanized mice”—immune deficient animals transplanted with human blood-forming cells. When such cells enter the brain, they transform into just the types of cells thought to harbor the HIV reservoir.

The researchers also focused on a drug, phenelzine (Nardil), currently used to treat depression that doesn’t respond to other medications and is able to enter the brain. Phenelzine stimulated HIV production from human microglial cells recovered from the brains of the HIV-infected humanized mice.

The authors felt that their model, and this new form of LRA, or latency reversing agent, shows “great promise as a model system for the development of strategies aimed at defining and reducing the central nervous system [brain] reservoir.”

Dr. Laurence is amfAR’s senior scientific consultant.