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BST2/Tetherin Overexpression Modulates Morbillivirus Glycoprotein Production to Inhibit Cell-Cell Fusion

James T Kelly1, Stacey Human1, Joseph Alderman2

  • 1Viral Glycoproteins Group, The Pirbright Institute, Ash Rd, Guildford, Surrey GU24 0NF, UK.

Viruses
|August 2, 2019
PubMed

Insights

Bone marrow stromal antigen 2 (BST2) inhibits measles virus (MeV) spread by blocking cell-cell fusion. This restriction targets the MeV hemagglutinin glycoprotein and is conserved across morbilliviruses.

Area of Science:

  • Virology
  • Immunology
  • Cell Biology

Background:

  • Measles virus (MeV) spreads through cell-cell fusion, a process crucial for syncytia formation.
  • Viral fusion (F) and hemagglutinin (H) glycoproteins drive MeV-mediated cell fusion.
  • Bone marrow stromal antigen 2 (BST2), also known as Tetherin, is an antiviral protein.

Purpose of the Study:

  • To investigate the role of BST2 in inhibiting measles virus (MeV) cell-cell fusion.
  • To identify the specific MeV glycoproteins targeted by BST2.
  • To determine if BST2's inhibitory effect is conserved across different morbilliviruses.

Main Methods:

  • Quantitative cell-cell fusion assays.
  • Immunolabeling and biochemical analyses.
  • Truncation mutant analysis of BST2.
  • In vitro and in vivo studies using MeV and peste des petits ruminants virus (PPRV).

Main Results:

  • BST2 overexpression significantly reduced MeV syncytia formation and cell-cell fusion.
  • BST2 directly inhibits MeV cell-cell fusion by targeting the MeV H glycoprotein.
  • The C-terminal glycosyl-phosphatidylinositol (GPI) anchor of BST2 is essential for its inhibitory function.
  • BST2 also restricts peste des petits ruminants virus (PPRV) replication and cell-cell fusion in sheep.

Conclusions:

  • BST2 acts as a broad-spectrum antiviral factor against morbilliviruses, including MeV and PPRV.
  • BST2's inhibition of morbillivirus spread is mediated through its GPI anchor and targets the viral H glycoprotein.
  • BST2 represents a potential therapeutic target for controlling morbillivirus infections.
Keywords:
BST2MeVMorbillivirusPPRVhaemagluttininmeaslestetherin

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