Short communication: Activating stimuli enhance immunotoxin-mediated killing of HIV-infected macrophages.
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.
Marsden
Matthew D
MD
Department of Medicine, Division of Hematology and Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA.
Xu
Jie
J
Hamer
Dean
D
Zack
Jerome A
JA
D019380:Anti-HIV Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D000922:Immunotoxins / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000821:virology; D008264:Macrophages / Q000187:drug effects* / Q000821:virology*; D010703:Phorbol Esters / Q000494:pharmacology
D019380:Anti-HIV Agents; D007155:Immunologic Factors; D000922:Immunotoxins; D010703:Phorbol Esters; C070999:prostratin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor