The lysosomal degradation pathway of autophagy has a crucial role in defence against infection, neurodegenerative disorders, cancer and ageing. Accordingly, agents that induce autophagy may have broad therapeutic applications. One approach to developing such agents is to exploit autophagy manipulation strategies used by microbial virulence factors. Here we show that a peptide, Tat–beclin 1—derived from a region of the autophagy protein, beclin 1, which binds human immunodeficiency virus (HIV)-1 Nef—is a potent inducer of autophagy, and interacts with a newly identified negative regulator of autophagy, GAPR-1 (also called GLIPR2). Tat–beclin 1 decreases the accumulation of polyglutamine expansion protein aggregates and the replication of several pathogens (including HIV-1) in vitro, and reduces mortality in mice infected with chikungunya or West Nile virus. Thus, through the characterization of a domain of beclin 1 that interacts with HIV-1 Nef, we have developed an autophagy-inducing peptide that has potential efficacy in the treatment of human diseases. A cell-permeable peptide is constructed that is derived from a region of an essential autophagy protein called beclin 1; the peptide is a potent inducer of autophagy in mammalian cells and in vivo in mice, and is effective in the clearance of several viruses. Autophagy is an essential degradation pathway that eliminates damaged proteins and organelles in cells and also protects against infection by diverse pathogens, including viruses. In this study, Beth Levine and colleagues construct a cell-permeable peptide, Tat-beclin 1, derived from part of an essential autophagy protein called beclin 1. This peptide is a potent inducer of autophagy in mammalian cells and in vivo in mice, and was effective in the clearance of several viruses including chikungunya virus, West Nile virus and HIV-1. The Tat-beclin 1 peptide binds to the Golgi-associated plant pathogenesis-related protein 1 (GAPR-1), which functions as a negative regulator of autophagy. These results suggest that this beclin 1-derived autophagy-inducing peptide has potential for the prevention and treatment of a broad range of human diseases.

Identification of a candidate therapeutic autophagy-inducing peptide