Requirements within the Ebola Viral Glycoprotein for Tetherin Antagonism
AbstractTetherin is an interferon-induced, intrinsic cellular response factor that blocks release of numerous viruses, including Ebola virus, from infected cells. As with many viruses targeted by host factors, Ebola virus employs a tetherin antagonist, the viral glycoprotein (EboGP), to counteract restriction and promote virus release. Unlike other tetherin antagonists such as HIV-1 Vpu or KSHV K5, the features within EboGP needed to overcome tetherin are not well characterized. Here, we describe sequences within the EboGP ectodomain and membrane spanning domain (msd) as necessary to relieve tetherin restriction of viral particle budding. Fusing the EboGP msd to a normally secreted form of the glycoprotein effectively promotes Ebola virus particle release. Cellular protein or lipid anchors could not substitute for the EboGP msd. The requirement for the EboGP msd was not specific for filovirus budding, as similar results were seen with HIV particles. Furthermore trafficking of chimeric proteins to budding sites did not correlate with an ability to counter tetherin. Additionally, we find that a glycoprotein construct, which mimics the cathepsin-activated species by proteolytic removal of the EboGP glycan cap and mucin domains, is unable to counteract tetherin. Combining these results suggests an important role for the EboGP glycan cap and msd in tetherin antagonism. View Full-Text
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Vande Burgt, N.H.; Kaletsky, R.L.; Bates, P. Requirements within the Ebola Viral Glycoprotein for Tetherin Antagonism. Viruses 2015, 7, 5587-5602.
Vande Burgt NH, Kaletsky RL, Bates P. Requirements within the Ebola Viral Glycoprotein for Tetherin Antagonism. Viruses. 2015; 7(10):5587-5602.Chicago/Turabian Style
Vande Burgt, Nathan H.; Kaletsky, Rachel L.; Bates, Paul. 2015. "Requirements within the Ebola Viral Glycoprotein for Tetherin Antagonism." Viruses 7, no. 10: 5587-5602.