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Cooperative Chikungunya virus membrane fusion and its sub-stoichiometric inhibition by CHK-152 antibody

Journal Article


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. 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 antibody.

Publication Date


  • 2020

Citation


  • Blijleven, J., Bouma, E., van Duijl, M. K. S., Smit, J., & van Oijen, A. (2020). Cooperative Chikungunya virus membrane fusion and its sub-stoichiometric inhibition by CHK-152 antibody. doi:10.1101/2020.03.18.996512

Web Of Science Accession Number


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. 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 antibody.

Publication Date


  • 2020

Citation


  • Blijleven, J., Bouma, E., van Duijl, M. K. S., Smit, J., & van Oijen, A. (2020). Cooperative Chikungunya virus membrane fusion and its sub-stoichiometric inhibition by CHK-152 antibody. doi:10.1101/2020.03.18.996512

Web Of Science Accession Number