Abstract: The host cell protein tetherin can restrict the release of enveloped viruses from infected cells. The HIV-1 protein Vpu counteracts tetherin by removing it from the site of viral budding, the plasma membrane, and this process depends on specific interactions between the transmembrane domains of Vpu and tetherin. In contrast, the glycoproteins (GPs) of two filoviruses, Ebola and Marburg virus, antagonize tetherin without reducing surface expression, and the domains in GP required for tetherin counteraction are unknown. Here, we show that filovirus GPs depend on the presence of their authentic transmembrane domains for virus-cell fusion and tetherin antagonism. However, conserved residues within the transmembrane domain were dispensable for membrane fusion and tetherin counteraction. Moreover, the insertion of the transmembrane domain into a heterologous viral GP, Lassa virus GPC, was not sufficient to confer tetherin antagonism to the recipient. Finally, mutation of conserved residues within the fusion peptide of Ebola virus GP inhibited virus-cell fusion but did not ablate tetherin counteraction, indicating that the fusion peptide and the ability of GP to drive host cell entry are not required for tetherin counteraction. These results suggest that the transmembrane domains of filoviral GPs contribute to tetherin antagonism but are not the sole determinants.
Keywords: tetherin; ebola; lassa; glycoprotein
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Gnirß, K.; Fiedler, M.; Krämer-Kühl, A.; Bolduan, S.; Mittler, E.; Becker, S.; Schindler, M.; Pöhlmann, S. Analysis of Determinants in Filovirus Glycoproteins Required for Tetherin Antagonism. Viruses 2014, 6, 1654-1671.
Gnirß K, Fiedler M, Krämer-Kühl A, Bolduan S, Mittler E, Becker S, Schindler M, Pöhlmann S. Analysis of Determinants in Filovirus Glycoproteins Required for Tetherin Antagonism. Viruses. 2014; 6(4):1654-1671.
Gnirß, Kerstin; Fiedler, Marie; Krämer-Kühl, Annika; Bolduan, Sebastian; Mittler, Eva; Becker, Stephan; Schindler, Michael; Pöhlmann, Stefan. 2014. "Analysis of Determinants in Filovirus Glycoproteins Required for Tetherin Antagonism." Viruses 6, no. 4: 1654-1671.