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Updated: Jun 21, 2026

Measuring Endoplasmic Reticulum Stress and Unfolded Protein Response in HIV-1 Infected T-Cells and Analyzing its Role in HIV-1 Replication
Published on: June 14, 2024
Small molecule targets Env for endoplasmic reticulum-associated protein degradation and inhibits human
Alenka Jejcic1, Robert Daniels, Laura Goobar-Larsson
1Department of Laboratory Medicine, Division of Clinical Microbiology, Karolinska Institutet, Stockholm, SE-141 86, Sweden.
Abstract:
Human immunodeficiency virus type 1 (HIV-1) is dependent on its envelope glycoprotein (Env) to bind, fuse, and subsequently infect a cell. We show here that treatment of HIV-1-infected cells with glycyl-prolyl-glycine amide (GPG-NH(2)), dramatically reduced the infectivity of the released viral particles by decreasing their Env incorporation. The mechanism of GPG-NH(2) was uncovered by examining Env expression and maturation in treated cells. GPG-NH(2) treatment was found to affect Env by significantly decreasing its steady-state levels, its processing into gp120/gp41, and its mass by inducing glycan removal in a manner dependent on its native signal sequence and the proteasome. Therefore, GPG-NH(2) negatively impacts Env maturation, facilitating its targeting for endoplasmic reticulum-associated protein degradation, where Env is deglycosylated en route to its degradation. These findings illustrate that nontoxic drugs such as GPG-NH(2), which can selectively target glycoproteins to existing cellular degradation pathways, may be useful for pathogen therapy.
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