Influence of amphipathic peptides on the HIV-1 production in persistently infected T lymphoma cells.

The effects of several amphipathic peptides on HIV-1 production in persistently infected cells are described. Melittin, a 26 amino acid α-helical amphipathic peptide, reduces HIV-1 production dose-dependently, whereas other amphipathic peptides do not. Six melittin derivatives which retain the α-helical portion have similar effects as melittin. The reduction of viral infectivity is not due to an effect of melittin on the virus particles but to an intracellular action of the peptide, which is readily taken up into cells, as shown by quantitative ELISA. Western blots of cells from melittin-treated cultures suggest that the processing of the gag/pol precursor is impaired

HIV-1 Nef protein exhibits structural and functional similarity to scorpion peptides interacting with K+ channels.

The persistent infection of human glial cells with HIV-1 is characterized by prominent expression of the Nef protein. In order to evaluate the possible role of Nef in the development of HIV-1-associated neurological disorders, we compared Nef with known neuroactive proteins. We found that HIV Nef shares sequence and structural features with scorpion peptides known to interact with K+ channels. Sequence similarity encompasses two distinct regions of scorpion peptides. Based on crystallography data, both regions in scorpion peptides cooperate in forming a common domain stabilized by ion pairs between charged amino-acid residues. Recombinant Nef protein, as well as a synthetic part of a scorpion channel active peptide (M10), reversibly increased the total K+ current of chick dorsal root ganglions in patch-clamp experiments without killing the cells. These results indicate that a region conserved in HIV Nef and scorpion peptides concurs in both structure and electrophysiological activity and suggest that Nef, like scorpion peptides, may affect neuronal cell function