A mutation in the human immunodeficiency virus type 1 transmembrane glycoprotein gp41 dominantly interferes with fusion and infectivity.
Several domains of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein have been identified that are involved in HIV-1-mediated membrane fusion. One domain that is involved in membrane fusion is the hydrophobic amino terminus of the HIV-1 transmembrane glycoprotein gp41. Here we show that a polar substitution at gp41 amino acid 2 (the 41.2 mutation) results in an envelope glycoprotein that dominantly interferes with both syncytium formation and infection mediated by the wild-type HIV-1 envelope glycoprotein. The interference by the 41.2 mutant is not a result of aberrant envelope glycoprotein synthesis, processing, or transport. The 41.2 mutant elicits a dominant interfering effect even in the presence of excess wild-type glycoprotein, suggesting that a higher-order envelope glycoprotein complex is involved in membrane fusion. These results shed light on the process by which the HIV-1 envelope glycoproteins induce membrane fusion reactions and present a possible approach to anti-HIV therapy.
Freed
E O
EO
McArdle Laboratory for Cancer Research, University of Wisconsin, Madison 53706.
Delwart
E L
EL
Buchschacher
G L
GL
Panganiban
A T
AT
D015704:CD4 Antigens / Q000378:metabolism; D002459:Cell Fusion; D002460:Cell Line; D004252:DNA Mutational Analysis; D015700:HIV Envelope Protein gp41 / Q000502:physiology*; D015497:HIV-1 / Q000235:genetics* / Q000472:pathogenicity; D015498:HIV-2 / Q000502:physiology; D066298:In Vitro Techniques; D008561:Membrane Fusion
D015704:CD4 Antigens; D015700:HIV Envelope Protein gp41