Open AccessA mutation in the human immunodeficiency virus type 1 transmembrane glycoprotein gp41 dominantly interferes with fusion and infectivity.
Author(s) -
Eric O. Freed,
Eric Delwart,
Gary L. Buchschacher,
Antonito T. Panganiban
Publication year - 1992
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.89.1.70
Subject(s) - gp41 , herpesvirus glycoprotein b , glycoprotein , lipid bilayer fusion , syncytium , biology , transmembrane protein , mutant , viral envelope , transmembrane domain , cell fusion , membrane glycoproteins , mutation , microbiology and biotechnology , viral entry , amino acid , virology , biochemistry , virus , viral replication , genetics , cell , gene , antibody , receptor , epitope
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.