Ebola Virus Glycoprotein Counteracts BST-2/Tetherin Restriction in a Sequence-Independent Manner That Does Not Require Tetherin Surface Removal
Autor: | Kevin G. Haworth, Lisa A Lopez, Heiko Hauser, Jill Oldenburg, Colin M. Exline, Paula M. Cannon, Su Jung Yang |
---|---|
Rok vydání: | 2010 |
Předmět: |
Recombinant Fusion Proteins
viruses Human Immunodeficiency Virus Proteins Molecular Sequence Data Immunology Population GPI-Linked Proteins medicine.disease_cause Microbiology Viral Envelope Proteins Viral envelope Antigens CD Virology medicine Animals Humans Viral Regulatory and Accessory Proteins Amino Acid Sequence Mononegavirales education education.field_of_study Membrane Glycoproteins Ebola virus Base Sequence biology Cell Membrane env Gene Products Human Immunodeficiency Virus Ebolavirus biology.organism_classification Virus Release Transmembrane protein Virus-Cell Interactions Protein Structure Tertiary Ectodomain Insect Science Tetherin HeLa Cells |
Zdroj: | Journal of Virology. 84:7243-7255 |
ISSN: | 1098-5514 0022-538X |
DOI: | 10.1128/jvi.02636-09 |
Popis: | BST-2/tetherin is an interferon-inducible protein that restricts the release of enveloped viruses from the surface of infected cells by physically linking viral and cellular membranes. It is present at both the cell surface and in a perinuclear region, and viral anti-tetherin factors including HIV-1 Vpu and HIV-2 Env have been shown to decrease the cell surface population. To map the domains of human tetherin necessary for both virus restriction and sensitivity to viral anti-tetherin factors, we constructed a series of tetherin derivatives and assayed their activity. We found that the cytoplasmic tail (CT) and transmembrane (TM) domains of tetherin alone produced its characteristic cellular distribution, while the ectodomain of the protein, which includes a glycosylphosphatidylinositol (GPI) anchor, was sufficient to restrict virus release when presented by the CT/TM regions of a different type II membrane protein. To counteract tetherin restriction and remove it from the cell surface, HIV-1 Vpu required the specific sequence present in the TM domain of human tetherin. In contrast, the HIV-2 Env required only the ectodomain of the protein and was sensitive to a point mutation in this region. Strikingly, the anti-tetherin factor, Ebola virus GP, was able to overcome restriction conferred by both tetherin and a series of functional tetherin derivatives, including a wholly artificial tetherin molecule. Moreover, GP overcame restriction without significantly removing tetherin from the cell surface. These findings suggest that Ebola virus GP uses a novel mechanism to circumvent tetherin restriction. |
Databáze: | OpenAIRE |
Externí odkaz: |