1887

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Volume 101, Issue 6

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

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 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.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): Arenaviridae , human BST-2 , innate immunity , Junin virus and Tetherin
Funding
This study was supported by the:
  • Japan Society for the Promotion of Science (JP) (Award JP17K157902)
    • Principle Award Recipient: Shuzo Urata
  • Japan Agency for Medical Research and Development (Award JP19fm0208101)
    • Principle Award Recipient: Jiro Yasuda
  • Japan Agency for Medical Research and Development (Award JP19fk0108072)
    • Principle Award Recipient: Jiro Yasuda
© 2020 The Authors
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2020-04-24
2024-04-24
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Human BST-2/tetherin inhibits Junin virus release from host cells and its inhibition is partially counteracted by viral nucleoprotein
J. Gen. Virol. 101, 573 (2020); https://doi.org/10.1099/jgv.0.001414
/content/journal/jgv/10.1099/jgv.0.001414
/content/journal/jgv/10.1099/jgv.0.001414
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