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Tat-beclin 1 is an autophagy-inducing peptide.1 It is composed of the HIV-1 Tat protein transduction domain linked via a diglycine linker to an 18-amino acid peptide corresponding to residues 267-284 of beclin-1 with amino acid substitutions at positions 275, 279, and 281 to enhance hydrophobicity. Tat-beclin 1 (30 µM) binds to the beclin-1-interacting protein Golgi-associated plant pathogenesis-related protein 1 (GAPR-1) in HeLa cells and induces conversion of LC3-I to LC3-II via lipidation and autophagosome formation in MCF-7 cells. It decreases viral titers in HeLa cells infected with Sindbis virus, chikungunya, or West Nile virus when used at a concentration of 10 µM. Tat-beclin 1 (0.5-5 µM) inhibits HIV p24 antigen release and viral replication in primary human monocyte-derived macrophages (MDMs). In vivo, Tat-beclin 1 (14 mg/kg) reduces intramuscular viral titers, neonatal mortality, and paralysis and increases muscle cell autophagosome formation in chikungunya-infected neonatal mice.
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1. Identification of a candidate therapeutic autophagy-