Analysis of determinants in filovirus glycoproteins required for tetherin antagonism.
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.
Infection Biology Unit, German Primate Center, 37077 Göttingen, Germany. KGnirss@dpz.eu.
Kerstin
K
Gnirß
Infection Biology Unit, German Primate Center, 37077 Göttingen, Germany. MFiedler@dpz.eu.
Marie
M
Fiedler
Infection Biology Unit, German Primate Center, 37077 Göttingen, Germany. annika.kraemer-kuehl@boehringer-ingelheim.com.
Annika
A
Krämer-Kühl
Institute of Virology, Helmholtz Center Munich, 85764 Neuherberg, Germany. sebastian.bolduan@helmholtz-muenchen.de.
Sebastian
S
Bolduan
Institute of Virology, Philipps-University-Marburg, 35043 Marburg, Germany. mittlere@staff.uni-marburg.de.
Eva
E
Mittler
Institute of Virology, Philipps-University-Marburg, 35043 Marburg, Germany. becker@staff.uni-marburg.de.
Stephan
S
Becker
Institute of Virology, Helmholtz Center Munich, 85764 Neuherberg, Germany. michael.schindler@helmholtz-muenchen.de.
Michael
M
Schindler
Infection Biology Unit, German Primate Center, 37077 Göttingen, Germany. spoehlmann@dpz.eu.
Stefan
S
Pöhlmann
D015703:Antigens, CD; D002460:Cell Line; D004252:DNA Mutational Analysis; D029043:Ebolavirus / Q000235:genetics / Q000502:physiology*; D058851:GPI-Linked Proteins / Q000037:antagonists & inhibitors; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D029024:Marburgvirus / Q000235:genetics / Q000502:physiology*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D000074010:Bone Marrow Stromal Antigen 2
D015703:Antigens, CD; D058851:GPI-Linked Proteins; D006023:Glycoproteins; D014764:Viral Proteins; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2