Abstract:
:The Nef protein of human immunodeficiency type 1 (HIV-1) has been implicated in diverse intracellular functions; however, extracellular functions have been less studied. Nef and the N-terminus of Nef possess membrane-perturbing and fusogenic activities in artificial membranes that also cause cytotoxicity to human cells, including lymphocytes. The present study investigates the toxicity of HIV-1 Nef peptides employing yeast and bacterial cells. The N-terminal portion of Nef was found to cause cell killing in Escherichia coli and in a variety of yeast cells. This activity was enhanced by myristylation of the Nef N-terminus, a modification that did not lead to toxicity in a control peptide. Cell death in yeast was due to permeabilization of the cell membrane as determined by the propidium iodide uptake of peptide-treated cells. Extracellular Nef, or its breakdown products, may have effects similar to the Nef peptides described here and could be responsible, at least in part, for the death of cells in lymphoid tissues during AIDS. Assays using yeast or bacteria are convenient, inexpensive, and robust and should be useful in further analysis and screening of inhibitors of this activity associated with HIV-1 Nef.
journal_name
Biochem Biophys Res Communjournal_title
Biochemical and biophysical research communicationsauthors
Macreadie IG,Lowe MG,Curtain CC,Hewish D,Azad AAdoi
10.1006/bbrc.1997.6349subject
Has Abstractpub_date
1997-03-27 00:00:00pages
707-11issue
3eissn
0006-291Xissn
1090-2104pii
S0006-291X(97)96349-Xjournal_volume
232pub_type
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