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

Jelle S. Blijleven, Ellen M. Bouma, Mareike K. S. van Duijl-Richter, Jolanda M. Smit, Antoine M. van Oijen*

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

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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.

Originele taal-2English
Aantal pagina's25
Nummer van het tijdschrift2
StatusPublished - feb.-2022

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