title: The Ebola virus glycoprotein and HIV-1 Vpu employ different strategies to counteract the antiviral factor tetherin.
abstract: The antiviral protein tetherin/BST2/CD317/HM1.24 restricts cellular egress of human immunodeficiency virus (HIV) and of particles mimicking the Ebola virus (EBOV), a hemorrhagic fever virus. The HIV-1 viral protein U (Vpu) and the EBOV-glycoprotein (EBOV-GP) both inhibit tetherin. Here, we compared tetherin counteraction by EBOV-GP and Vpu. We found that EBOV-GP but not Vpu counteracted tetherin from different primate species, indicating that EBOV-GP and Vpu target tetherin differentially. Tetherin interacted with the GP2 subunit of EBOV-GP, which might encode the determinants for tetherin counteraction. Vpu reduced cell surface expression of tetherin while EBOV-GP did not, suggesting that both proteins employ different mechanisms to counteract tetherin. Finally, Marburg virus (MARV)-GP also inhibited tetherin and downregulated tetherin in a cell type-dependent fashion, indicating that tetherin antagonism depends on the cellular source of tetherin. Collectively, our results indicate that EBOV-GP counteracts tetherin by a novel mechanism and that tetherin inhibition is conserved between EBOV-GP and MARV-GP.
authors: Institute of Virology, Hannover Medical School, Germany.
authors: Annika
authors: A
authors: Kühl
authors: Carina
authors: C
authors: Banning
authors: Andrea
authors: A
authors: Marzi
authors: Jörg
authors: J
authors: Votteler
authors: Imke
authors: I
authors: Steffen
authors: Stephanie
authors: S
authors: Bertram
authors: Ilona
authors: I
authors: Glowacka
authors: Andreas
authors: A
authors: Konrad
authors: Michael
authors: M
authors: Stürzl
authors: Ju-Tao
authors: JT
authors: Guo
authors: Ulrich
authors: U
authors: Schubert
authors: Heinz
authors: H
authors: Feldmann
authors: Georg
authors: G
authors: Behrens
authors: Michael
authors: M
authors: Schindler
authors: Stefan
authors: S
authors: Pöhlmann
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002474:Cell-Free System; D002522:Chlorocebus aethiops; D029043:Ebolavirus / Q000378:metabolism*; D058851:GPI-Linked Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006071:Gorilla gorilla; D054298:Human Immunodeficiency Virus Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008253:Macaca mulatta; D029024:Marburgvirus; D021122:Protein Subunits; D013045:Species Specificity; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics / Q000378:metabolism*; D000074010:Bone Marrow Stromal Antigen 2; D000086082:Viroporin Proteins
chemical_list: D015703:Antigens, CD; D058851:GPI-Linked Proteins; D006023:Glycoproteins; D054298:Human Immunodeficiency Virus Proteins; D021122:Protein Subunits; D054334:Viral Regulatory and Accessory Proteins; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins