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Snapin, Positive Regulator Of Stimulation- Induced Ca(2+) Release Through Ryr, Is Necessary For Hiv-1 Replication In T Cells., Shigemi M Kinoshita, Amane Kogure, Shizuka Taguchi, Garry P Nolan

Department of Microbiology and Immunology Faculty Papers

To identify critical host factors necessary for human immunodeficiency virus 1 (HIV-1) replication, large libraries of short-peptide-aptamers were expressed retrovirally. The target of one inhibitor peptide, Pep80, identified in this screen was determined to be Snapin, a protein associated with the soluble N-ethyl maleimide sensitive factor adaptor protein receptor (SNARE) complex that is critical for calcium-dependent exocytosis during neurotransmission. Pep80 inhibited Ca(2+) release from intracellular stores and blocked downstream signaling by direct interruption of the association between Snapin and an intracellular calcium release channel, the ryanodine receptor (RyR). NFAT signaling was preferentially abolished by Pep80. Expression of Snapin overcame Pep80-mediated …