Neutralizing Antibodies Inhibit Chikungunya Virus Budding at the Plasma Membrane

Details

• Alternative Title:
  Cell Host Microbe
• Personal Author:
  Jin, Jing ; Galaz-Montoya, Jesús G. ; Sherman, Michael B. ; Sun, Stella Y. ; Goldsmith, Cynthia S. ; O’Toole, Eileen T. ; Ackerman, Larry ; Carlson, Lars-Anders ; Weaver, Scott C. ; Chiu, Wah ; Simmons, Graham
• Description:
  Neutralizing antibodies (NAbs) are traditionally thought to inhibit virus infection by preventing virion entry into target cells. In addition, antibodies can engage Fc receptors (FcRs) on immune cells to activate antiviral responses. We describe a mechanism by which NAbs inhibit chikungunya virus (CHIKV), the most common alphavirus infecting humans, by preventing virus budding from infected human cells and activating IgG-specific Fcγ receptors. NAbs bind to CHIKV glycoproteins on the infected cell surface and induce glycoprotein coalescence, preventing budding of nascent virions and leaving structurally heterogeneous nucleocapsids arrested in the cytosol. Furthermore, NAbs induce clustering of CHIKV replication spherules at sites of budding blockage. Functionally, these densely packed glycoprotein-NAb complexes on infected cells activate Fcγ receptors, inducing a strong, antibody-dependent, cell-mediated cytotoxicity response from immune effector cells. Our findings describe a triply functional antiviral pathway for NAbs that might be broadly applicable across virus-host systems, suggesting avenues for therapeutic innovation through antibody design.
• Subjects:
  Antibodies, Neutralizing Antibodies, Viral Cell Line Cell Membrane Chikungunya Fever Chikungunya Virus Humans Virus Release Virus Replication
• Keywords:
  Chikungunya Virus (CHIKV) Cryo-electron Tomography (cryoET) Glycoproteins (GPs) Immunoelectron Microscopy (IEM) Neutralizing Antibodies (NAbs) Nucleocapsid-like Particles (NCLPs) Stimulated Emission Depletion Microscopy (STED) Subtomogram Averaging (STA) Transmission Electron Microscopy (TEM)
• Source:
  Cell Host Microbe. 24(3):417-428.e5
• Pubmed ID:
  30146390
• Pubmed Central ID:
  PMC6137268
• Document Type:
  Journal Article
• Funding:
  P41 GM103832/GM/NIGMS NIH HHSUnited States/ ; HHSN272200700055C/AI/NIAID NIH HHSUnited States/ ; HHSN272200900055C/AI/NIAID NIH HHSUnited States/ ; CC999999/Intramural CDC HHSUnited States/ ; R24 AI120942/AI/NIAID NIH HHSUnited States/ ; R01 AI119056/AI/NIAID NIH HHSUnited States/
• Volume:
  24
• Issue:
  3
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:42f0e987d5bf8bf686d5caf7898877c56f0cc40f8a6ba73ac9617dd8793e1f3c
• Download URL:
  https://stacks.cdc.gov/view/cdc/78515/cdc_78515_DS1.pdf
• File Type:
  [PDF - 2.68 MB ]