Human immunodeficiency virus 1 (HIV-1) Rev and integrase (IN) proteins are required within the nuclei of infected cells in the late and early phases of the viral replication cycle, respectively. Here we show using various biochemical methods, that these two proteins interact with each other in vitro and in vivo. Peptide mapping and fluorescence anisotropy showed that IN binds residues 1-30 and 49-74 of Rev. Following this observation, we identified two short Rev-derived peptides that inhibit the 3′-end processing and strand-transfer enzymatic activities of IN in vitro. The peptides bound IN in vitro, penetrated into cultured cells, and significantly inhibited HIV-1 in multinuclear activation of a galactosidase indicator (MAGI) and lymphoid cultured cells. Real time PCR analysis revealed that the inhibition of HIV-1 multiplication is due to inhibition of the catalytic activity of the viral IN. The present work describes novel anti-HIV-1 lead peptides that inhibit viral replication in cultured cells by blocking DNA integration in vivo.

In Alzheimer's disease, both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) colocalize with brain fibrils of amyloid-beta (Abeta) peptides, and synaptic AChE-S facilitates fibril formation by association with insoluble Abeta fibrils. Here, we report that human BChE and BSP41, a synthetic peptide derived from the BChE C terminus, inversely associate with the soluble Abeta conformers and delay the onset and decrease the rate of Abeta fibril formation in vitro, at a 1:100 BChE/Abeta molar ratio and in a dose-dependent manner. The corresponding AChE synthetic peptide (ASP)40 peptide, derived from the homologous C terminus of synaptic human (h)AChE-S, failed to significantly affect Abeta fibril formation, attributing the role of enhancing this process to an AChE domain other than the C terminus. Circular dichroism and molecular modeling confirmed that both ASP40 and BChE synthetic peptide (BSP)41 are amphipathic alpha-helices. However, ASP40 shows symmetric amphipathicity, whereas BSP41 presented an aromatic tryptophan residue in the polar side of the C terminus. That this aromatic residue is causally involved in the attenuating effect of BChE was further supported by mutagenesis experiments in which (W8R) BSP41 showed suppressed capacity to attenuate fibril formation. In Alzheimer's disease, BChE may have thus acquired an inverse role to that of AChE by adopting imperfect amphipathic characteristics of its C terminus.