Cooperative Chikungunya Virus Membrane Fusion and Its Substoichiometric Inhibition by CHK-152 Antibody

Viruses. 2022 Jan 28;14(2):270. doi: 10.3390/v14020270.

Abstract

Chikungunya virus (CHIKV) presents a major burden on healthcare systems worldwide, but specific treatment remains unavailable. Attachment and fusion of CHIKV to the host cell membrane is mediated by the E1/E2 protein spikes. We used an in vitro single-particle fusion assay to study the effect of the potent, neutralizing antibody CHK-152 on CHIKV binding and fusion. We find that CHK-152 shields the virions, inhibiting interaction with the target membrane and inhibiting fusion. The analysis of the ratio of bound antibodies to epitopes implied that CHIKV fusion is a highly cooperative process. Further, dissociation of the antibody at lower pH results in a finely balanced kinetic competition between inhibition and fusion, suggesting a window of opportunity for the spike proteins to act and mediate fusion, even in the presence of the antibody.

Keywords: chikungunya virus; membrane fusion; neutralizing antibody; single-particle.

MeSH terms

  • Animals
  • Antibodies, Neutralizing / immunology*
  • Antibodies, Neutralizing / metabolism
  • Antibodies, Viral / immunology*
  • Antibodies, Viral / metabolism
  • Cell Line
  • Chikungunya virus / immunology*
  • Chikungunya virus / physiology*
  • Hydrogen-Ion Concentration
  • Viral Fusion Proteins / chemistry
  • Viral Fusion Proteins / metabolism
  • Virion / physiology
  • Virus Attachment
  • Virus Internalization*

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Viral Fusion Proteins