Distinct Roles for Sialoside and Protein Receptors in Coronavirus Infection

Qing, Enya; Hantak, Michael; Perlman, Stanley; Gallagher, Tom

Sialic Acids Facilitate Coronavirus Dissemination ® While sialic acids affected virus-cell binding, infection by JHM-CoV and cell entry by MERS-CoV VLPs required the proteinaceous receptors mCEACAM and hDPP4, respectively. Therefore, one possibility is that multivalent CoV-sialate interactions are not sufficient to hold viruses throughout a virus particle-cell membrane fusion process and that sialic acids may instead only tether viruses, transiently, onto host cell surfaces, as they diffuse two-dimensionally and then bind more stably to high-affinity protein receptors. Yet, while insufficient for the initial infection, sialic acid binding may advance the spike-mediated cell-cell membrane fusions that are observed in several CoV infection processes. In cell-cell fusion, spikes on infectedcell surfaces are steadily directed at uninfected (target) cells. They are not liable to diffuse away as cell-bound viruses would, yet they still may require attachment to target cell sialates in order to effect membrane fusion. In support of this contention, we found correlations between sialic acid abundance and membrane fusion activity. This was observed for both JHM-and MERS-CoV spikes, and notably, both the JHMand MERS-CoV spike-directed cell fusions took place independently of any proteinaceous receptors. These correlations suggest that sialic acids on uninfected cells can arrange spikes such that they will then operate cooperatively to pull opposing plasma membranes into coalescence.