Short Communication:Activating Stimuli Enhance Immunotoxin-Mediated Killing of HIV-Infected Macrophages

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Abstract
Strategies for purging persistent reservoirs in human immunodeficiency virus (HIV)-infected individuals may be enhanced by including agents that specifically kill virus-expressing cells. Anti-HIV envelope immunotoxins (ITs) represent one class of candidate molecules that could fulfill this function. We have previously utilized an anti-gp120 IT in conjunction with various stimulants to kill latently infected T cells ex vivo. Here we show that primary macrophages expressing HIV Env are relatively refractory to killing by IT when used alone. However, including stimulants such as prostratin or granulocyte–macrophage colony-stimulating factor to increase HIV gene expression in infected macrophages enhanced IT-mediated killing. Therefore, “activation–elimination” strategies similar to those proposed for purging the latent HIV reservoir may prove useful in clearing chronically infected macrophages in vivo.