High-Mannose But Not Complex-Type Glycosylation of Tetherin Is Required for Restriction of HIV-1 Release

Viruses
Abdul A WaheedEric O Freed

Abstract

Tetherin is an interferon-inducible antiviral protein that inhibits the release of a broad spectrum of enveloped viruses by retaining virions at the surface of infected cells. While the role of specific tetherin domains in antiviral activity is clearly established, the role of glycosylation in tetherin function is not clear. In this study, we carried out a detailed investigation of this question by using tetherin variants in which one or both sites of N-linked glycosylation were mutated (N65A, N92A, and N65,92A), and chemical inhibitors that prevent glycosylation at specific stages of oligosaccharide were added or modified. The single N-linked glycosylation mutants, N65A and N92A, efficiently inhibited the release of Vpu-defective human immunodeficiency virus type 1 (HIV-1). In contrast, the non-glycosylated double mutant, N65,92A, lost its ability to block HIV-1 release. The inability of the N65,92A mutant to inhibit HIV-1 release is associated with a lack of cell-surface expression. A role for glycosylation in cell-surface tetherin expression is supported by tunicamycin treatment, which inhibits the first step of N-linked glycosylation and impairs both cell-surface expression and antiviral activity. Inhibition of complex-type...Continue Reading

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Citations

Jun 12, 2019·PeerJ·Ian R RoyChristopher E Berndsen
May 18, 2021·Frontiers in Immunology·Yuqing LiWeijie Dong
Jul 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Irene MaierGeorg Kontaxis

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Methods Mentioned

BETA
glycosylation
transfection
electrophoresis
fluorescence-activated cell sorting
flow cytometry

Software Mentioned

TreeStar
FlowJo

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