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Human BST-2/tetherin inhibits Junin virus release from host cells and its inhibition is partially counteracted by viral nucleoprotein


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Title: Human BST-2/tetherin inhibits Junin virus release from host cells and its inhibition is partially counteracted by viral nucleoprotein
Authors: Zadeh, Vahid Rajabali / Urata, Shuzo / Sakaguchi, Miako / Yasuda, Jiro
Issue Date: 24-Apr-2020
Publisher: Microbiology soceity
Citation: Journal of general virology, 101(6), pp.573-586; 2020
Abstract: Bone marrow stromal cell antigen-2 (BST-2), also known as tetherin, is an interferon-inducible membrane-associated protein. It effectively targets enveloped viruses at the release step of progeny viruses from host cells, thereby restricting the further spread of viral infection. Junin virus (JUNV) is a member of Arenaviridae, which causes Argentine haemorrhagic fever that is associated with a high rate of mortality. In this study, we examined the effect of human BST-2 on the replication and propagation of JUNV. The production of JUNV Z-mediated virus-like particles (VLPs) was significantly inhibited by over-expression of BST-2. Electron microscopy analysis revealed that BST-2 functions by forming a physical link that directly retains VLPs on the cell surface. Infection using JUNV showed that infectious JUNV production was moderately inhibited by endogenous or exogenous BST-2. We also observed that JUNV infection triggers an intense interferon response, causing an upregulation of BST-2, in infected cells. However, the expression of cell surface BST-2 was reduced upon infection. Furthermore, the expression of JUNV nucleoprotein (NP) partially recovered VLP production from BST-2 restriction, suggesting that the NP functions as an antagonist against antiviral effect of BST-2. We further showed that JUNV NP also rescued the production of Ebola virus VP40-mediated VLP from BST-2 restriction as a broad spectrum BST-2 antagonist. To our knowledge, this is the first report showing that an arenavirus protein counteracts the antiviral function of BST-2.
Keywords: Junin virus / Arenaviridae / human BST-2 / innate immunity / Tetherin
URI: http://hdl.handle.net/10069/40142
ISSN: 00221317
DOI: 10.1099/jgv.0.001414
Rights: © 2020 The Authors. Published by the Microbiology Society. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/
Type: Journal Article
Text Version: publisher
Appears in Collections:Articles in academic journal

Citable URI : http://hdl.handle.net/10069/40142

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