A Mutation in the Human Immunodeficiency Virus Type 1 Transmembrane Glycoprotein Gp41 Dominantly Interferes with Fusion and Infectivity

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1992 Jan 11

PMID 1729720

Citations 140

Authors

E O Freed

E L Delwart

G L Buchschacher Jr

A T Panganiban

Affiliations

Soon will be listed here.

Abstract

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.

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