Inhibition of Lassa and Marburg Virus Production by Tetherin

Abstract

Recently, tetherin has been identified as an effective cellular factor that prevents the release of human immunodeficiency virus type 1. Here, we show that the production of virus-like particles induced by viral matrix proteins of Lassa virus or Marburg virus was markedly inhibited by tetherin and that N-linked glycosylation of tetherin was dispensable for this antiviral activity. Our data also suggest that viral matrix proteins or one or more components that originate from host cells are targets of tetherin but that viral surface glycoproteins are not. These results suggest that tetherin inhibits the release of a wide variety of enveloped viruses from host cells by a common mechanism.

Simian immunodeficiency virus envelope glycoprotein counteracts tetherin/BST-2/CD317 by intracellular sequestration

“…It is proposed to form a protein tether linking assembled virions to infected cells, leading to their endocytosis and degradation in lysosomes (1,6). All tetherin variants tested thus far inhibit the release of enveloped viral particles including retroviruses, filoviruses, and arena viruses (1,2,(7)(8)(9)(10). Many simian immunodeficiency variants do not encode a Vpu protein, suggesting the existence of an alternative means of overcoming tetherin restriction.…”

Tetherin antagonism by Vpu protects HIV-infected cells from antibody-dependent cell-mediated cytotoxicity

“…This activity can be explained by the unusual topology of tetherin, which includes an N-terminal transmembrane domain and a C-terminal glycosyl-phosphatidylinositol tail that allow both ends of the molecule to be anchored in lipid membranes (4). Although tetherin was initially identified as the cellular gene product that accounts for a late-stage defect in the release of vpu-deleted HIV-1 from restrictive cells (5,6), it is now recognized to have antiviral activity against diverse families of enveloped viruses (7)(8)(9)(10)(11).…”

CD4 and BST-2/Tetherin Proteins Retro-translocate from Endoplasmic Reticulum to Cytosol as Partially Folded and Multimeric Molecules

“…Tetherin, however, is a cellular viral restriction factor that is able to antagonize the spreading of enveloped viruses (including HIV-1) by tethering newly formed viral particles to the plasma membrane of infected cells (13)(14)(15)(16). Structurally, Tetherin is a type II transmembrane protein with a glycosylphosphatidylinositol (GPI) anchor at its C terminus that forms covalent dimers by three interchain disulfide bridges between two parallel monomers (17,18).…”