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.
Highlights
Viruses 2022, 14, 270. https://The chikungunya virus (CHIKV; Alphavirus genus, Togaviridae family) is a human arthropod-borne virus causing chikungunya fever and potentially long-lasting effects, such as joint pain
We found that CHK-152 strongly interferes with CHIKV membrane interactions, both at neutral and low pH
Using a single-particle fluorescence assay and a substoichiometric ratio of CHK-152 binding, virions were pre-docked to a membrane
Summary
The chikungunya virus (CHIKV; Alphavirus genus, Togaviridae family) is a human arthropod-borne virus causing chikungunya fever and potentially long-lasting effects, such as joint pain. It has recently greatly expanded its geographic range to encompass most tropical-to-temperate regions of the world [1] and is likely to spread further, due to geographic expansion of the mosquito vectors that transmit the virus [2,3,4]. The membrane encapsulates the protein capsid in which the viral genome resides. E1 and E2, are anchored into the membrane and arranged in trimers of E1/E2 heterodimers called spikes.
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