Inhibition of human immunodeficiency virus envelope glycoprotein- mediated single cell lysis by low-molecular-weight antagonists of viral entry.
The coexpression of human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins and receptors leads to the lysis of single cells by a process that is dependent upon membrane fusion. This cell lysis was inhibited by low-molecular-weight compounds that interfere with receptor binding or with receptor-induced conformational transitions in the envelope glycoproteins. A peptide, T20, potently inhibited cell-cell fusion but had no effect on single cell lysis mediated by the HIV-1 envelope glycoproteins. Thus, critical events in the lysis of single cells by the HIV-1 envelope glycoproteins occur in intracellular compartments accessible only to small inhibitory compounds.
Madani
Navid
N
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Hubicki
Amy M
AM
Perdigoto
Ana Luisa
AL
Springer
Martin
M
Sodroski
Joseph
J
D000818:Animals; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D004285:Dogs; D000077560:Enfuvirtide; D004987:Ethers / Q000494:pharmacology*; D015686:Gene Products, env / Q000378:metabolism*; D015700:HIV Envelope Protein gp41 / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects* / Q000472:pathogenicity*; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000494:pharmacology*; D008561:Membrane Fusion / Q000187:drug effects*; D008970:Molecular Weight; D010446:Peptide Fragments / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*
C451732:BMS 806; D004987:Ethers; D015686:Gene Products, env; D015700:HIV Envelope Protein gp41; D006845:Hydrocarbons, Fluorinated; D010446:Peptide Fragments; D010879:Piperazines; D000077560:Enfuvirtide; C078742:fluoromethyl 2,2-difluoro-1-(trifluoromethyl)vinyl ether