June 12, 2015

New strategy to combat HIV

Inhibitors of the enzyme phospholipase D1 suppress the replication of HIV-1, Vanderbilt investigators have discovered.

HIV cell

Researchers at Northwestern and Vanderbilt universities have discovered a potential new way to thwart human immunodeficiency virus type 1 (HIV-1).

The target is phospholipase D1 (PLD1), an enzyme involved in the activation of a certain kind of immune cell, the CD4+ T cell. HIV-1 preferentially invades this cell and, at the same time that the cell is activated, robs the cell of nutrients, including glucose and DNA building blocks, so it can’t replicate its own genome.

Last month in the journal PLOS Pathogens, H. Alex Brown, Ph.D., Craig W. Lindsley, Ph.D., and colleagues reported that the PLD1 signaling pathway couples T cell activation to HIV-1 replication, and that a small molecule inhibitor of PLD1 can suppress HIV-1 replication.

The discovery could lead to the development of compounds that suppress HIV as well as other retroviruses and cancer. Last year, Brown, Lindsley and colleagues reported that PLD inhibitors blocked cancerous growth in laboratory and animal models.

The research was reported in part by National Institutes of Health grants MH084659, DK094735, RR024977 and CA060553.

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